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10.1162/089976699300016133
39,985,527
Peaks in spike train correlograms are usually taken as indicative of spike timing synchronization between neurons. Strictly speaking, however, a peak merely indicates that the two spike trains were not independent. Two biologically plausible ways of departing from independence that are capable of generating peaks very ...
10.1038/35086012
Points out several ways in which peaks might arise in cross-correlation histograms. An important reference for anyone using this method.
10.1126/science.278.5345.1950
125,080,592
It is now commonly accepted that planning and execution of movements are based on distributed processing by neuronal populations in motor cortical areas. It is less clear, though, how these populations organize dynamically to cope with the momentary computational demands. Simultaneously recorded activities of neurons i...
10.1038/35086012
This study exploits a simple, yet creative, behavioural model to study synchronization in the primary motor cortex. Neurons in this area become transiently synchronized when a stimulus appears, or when it is expected to appear but it does not. In the former case, mean firing rates typically change with (but independent...
10.1126/science.1055465
123,192,102
In crowded visual scenes, attention is needed to select relevant stimuli. To study the underlying mechanisms, we recorded neurons in cortical area V4 while macaque monkeys attended to behaviorally relevant stimuli and ignored distracters. Neurons activated by the attended stimulus showed increased gamma-frequency (35 t...
10.1038/35086012
The responses of visual neurons were compared when attention was directed inside or outside their receptive fields, for the same stimulus. Extreme care was taken to minimize changes in mean firing rate and to measure synchrony in an unbiased way. When attention shifts to the recorded neuron's receptive field, the unit ...
10.1073/pnas.94.23.12699
125,306,680
In subjects suffering from early onset strabismus, signals conveyed by the two eyes are not perceived simultaneously but in alternation. We exploited this phenomenon of interocular suppression to investigate the neuronal correlate of binocular rivalry in primary visual cortex of awake strabismic cats. Monocularly prese...
10.1038/35086012
A study of V1 responses in an experimental set-up in which firing rates did not vary, but perceptual experience did. Robust changes in synchrony were observed from one perceptual condition to another. Even if the nature of the perceptual process is questioned, it is remarkable that synchrony in V1 can be so strongly mo...
10.1073/pnas.98.3.1282
110,848,722
A previous paper described a network of simple integrate-and-fire neurons that contained output neurons selective for specific spatiotemporal patterns of inputs; only experimental results were described. We now present the principles behind the operation of this network and discuss how these principles point to a gener...
10.1038/35086012
A model for speech recognition in which a set of sensory units responds, a downstream population becomes activated and synchronized, and a third population further downstream responds selectively to the evoked synchrony patterns. The model shows how oscillations generated centrally could confer a functional advantage t...
10.1242/dev.120.3.613
125,326,250
The anterior aspect of the mouse primitive streak resembles the organizer of Xenopus and chick in terms of its developmental fate, ability to alter pattern in the chick limb bud and with respect to the repertoire of genes that its constituent cells express. However, until now there has been no direct evidence that the ...
10.1038/35053563
In this paper, Beddington shows that a graft of the mouse node induces an ectopic neural axis that lacks the most rostral structures.
10.1242/dev.126.22.5171
104,234,430
Fragments of the germ layer tissues isolated from the early-primitive-streak (early-streak) stage mouse embryos were tested for axis induction activity by transplantation to late-gastrula (late-streak to early-bud) stage host embryos. The posterior epiblast fragment that contains the early gastrula organizer was able t...
10.1038/35053563
Sophisticated recombination experiments show that tissues other than the anterior visceral endoderm are required for forebrain specification in the mouse.
10.1242/dev.118.1.139
38,291,752
We have developed germ layer explant culture assays to study the role of mesoderm in anterior-posterior (A-P) patterning of the mouse neural plate. Using isolated explants of ectodermal tissue alone, we have demonstrated that the expression of Engrailed-1 (En-1) and En-2 genes in ectoderm is independent of mesoderm by ...
10.1038/35053563
The first clear demonstration that the mouse mesendoderm has a distinct patterning role, as well as 'rostralizing' activity.
10.1242/dev.127.17.3839
123,054,766
Several models have been proposed for the generation of the rostral nervous system. Among them, Nieuwkoop's activation/transformation hypothesis and Spemann's idea of separate head and trunk/tail organizers have been particularly favoured recently. In the mouse, the finding that the visceral endoderm (VE) is required f...
10.1038/35053563
The chick hypoblast directs cell movements in the adjacent epiblast and induces transient expression of neural and forebrain markers, but does not provide sufficient signals to commit cells to either a neural or a forebrain fate.
10.4049/jimmunol.165.9.5069
102,482,792
Abstract Chemokines play an important role in the migration of leukocytes at sites of inflammation, and some constitutively expressed chemokines may direct lymphocyte trafficking within lymphoid organs and peripheral tissues. Thymus-expressed chemokine (TECK or Ckβ-15/CCL25), which signals through the chemokine recepto...
10.1038/35095573
References 23–26 show that, in both mice and humans, tissue-specific expression of thymocyte-expressed chemokine (TECK) recruits CCR9 + lymphocytes to the small intestine.
10.1152/ajpgi.2001.280.4.g710
10,318,486
Human intestinal epithelial cells secrete an array of chemokines known to signal the trafficking of neutrophils and monocytes important in innate mucosal immunity. We hypothesized that intestinal epithelium may also have the capacity to play a role in signaling host adaptive immunity. The CC chemokine macrophage inflam...
10.1038/35095573
References 41–43 show that CCR-6/MIP-3α is a second chemokine/receptor pair (the other is CCR9/CCL25) that is specific for the intestinal epithelium. The secretion of MIP-3α by the intestinal epithelium recruits CCR6 + dendritic cells into the intestinal mucosa.
10.1126/science.289.5484.1560
4,671,813
Epithelia of the vertebrate intestinal tract characteristically maintain an inflammatory hyporesponsiveness toward the lumenal prokaryotic microflora. We report the identification of enteric organisms (nonvirulent Salmonella strains) whose direct interaction with model human epithelia attenuate synthesis of inflammator...
10.1038/35095573
Reports that binding of non-pathogenic bacteria to intestinal epithelial cells in vitro impairs transcription of pro-inflammatory cytokines by blocking the NF-κB/IκB signalling pathway.
10.1084/jem.191.3.435
83,484,247
This study identifies a dendritic cell (DC) subset that constitutively transports apoptotic intestinal epithelial cell remnants to T cell areas of mesenteric lymph nodes in vivo. Rat intestinal lymph contains two DC populations. Both populations have typical DC morphology, are major histocompatibility complex class IIh...
10.1038/35095573
Dendritic cell (DC) migration had been thought to require exposure to an inflammatory stimulus. This report shows that a subpopulation of DCs continuously tranports epithelial cell remnants (and presumably other antigens) from the intestinal mucosa to the T-cell areas of the mesenteric lymph node.
10.1126/science.283.5405.1152
104,327,139
A single kinesin molecule can move “processively” along a microtubule for more than 1 micrometer before detaching from it. The prevailing explanation for this processive movement is the “walking model,” which envisions that each of two motor domains (heads) of the kinesin molecule binds coordinately to the microtubule....
10.1038/35036069
Experimental evidence for the directional movement of single monomeric kinesin molecules.
10.1073/pnas.98.4.1601
62,571,922
The two widely coexpressed isoforms of β-arrestin (termed βarrestin 1 and 2) are highly similar in amino acid sequence. The β-arrestins bind phosphorylated heptahelical receptors to desensitize and target them to clathrin-coated pits for endocytosis. To better define differences in the roles of β-arrestin 1 and 2, we p...
10.1038/35094577
Using cells from mouse embryos lacking β-arrestin 1, β-arrestin 2 or both, the authors show the central roles of β-arrestins in GPCR desensitization, internalization and downregulation.
10.1126/science.286.5449.2495
122,962,028
The ability of morphine to alleviate pain is mediated through a heterotrimeric guanine nucleotide binding protein (G protein)–coupled heptahelical receptor (GPCR), the μ opioid receptor (μOR). The efficiency of GPCR signaling is tightly regulated and ultimately limited by the coordinated phosphorylation of the receptor...
10.1038/35094577
Using mice lacking β-arrestin 2, Bohn et al . show the crucial role of β-arrestin 2 in the development of tolerance to opioids.
10.1126/science.290.5496.1574
59,416,221
β-Arrestins, originally discovered in the context of heterotrimeric guanine nucleotide binding protein–coupled receptor (GPCR) desensitization, also function in internalization and signaling of these receptors. We identified c-Jun amino-terminal kinase 3 (JNK3) as a binding partner of β-arrestin 2 using a yeast two-hyb...
10.1038/35094577
Shows that β-arrestin 2, but not β-arrestin 1, scaffolds the sequentially acting kinases in the JNK3 cascade, leading to the activation and cytosolic retention of JNK3. So, in addition to their roles in turning off GPCR signalling pathways, β-arrestins also promote GPCR signalling.
10.1126/science.280.5360.69
83,368,665
The potassium channel from Streptomyces lividans is an integral membrane protein with sequence similarity to all known K + channels, particularly in the pore region. X-ray analysis with data to 3.2 angstroms reveals that four identical subunits create an inverted teepee, or cone, cradling the selectivity filter of the ...
10.1038/35090015
This landmark paper presents the first crystal structure of a P-loop-containing channel, KcsA.
10.1126/science.285.5424.73
58,564,361
The intramembrane molecular events underlying activation gating in the Streptomyces K + channel were investigated by site-directed spin-labeling methods and electron paramagnetic resonance spectroscopy. A comparison of the closed and open conformations of the channel revealed periodic changes in spin-label mobility and...
10.1038/35090015
Electron paramagnetic resonance spectroscopy experiments indicate that the opening of KcsA involves a translation and rotation of the TM1 and TM2 segments.
10.1085/jgp.117.2.165
1,340,658
The molecular architecture of the NH2 and COOH termini of the prokaryotic potassium channel KcsA has been determined using site-directed spin-labeling methods and paramagnetic resonance EPR spectroscopy. Cysteine mutants were generated (residues 5–24 and 121–160) and spin labeled, and the X-band CW EPR spectra were obt...
10.1038/35090015
Electron paramagnetic resonance spectroscopy experiments show that the post-TM region of KcsA forms a helical bundle.
10.1126/science.287.5461.2204
62,616,040
A comparative analysis of the genomes of Drosophila melanogaster , Caenorhabditis elegans , and Saccharomyces cerevisiae —and the proteins they are predicted to encode—was undertaken in the context of cellular, developmental, and evolutionary processes. The nonredundant protein sets of flies and worms are similar in si...
10.1038/35048107
References 9 and 10 are an excellent source for comparative genomics in worms, yeast and flies.
10.1083/jcb.148.4.635
82,969,408
An understanding of how the nuclear pore complex (NPC) mediates nucleocytoplasmic exchange requires a comprehensive inventory of the molecular components of the NPC and a knowledge of how each component contributes to the overall structure of this large molecular translocation machine. Therefore, we have taken a compre...
10.1038/35048107
This paper describes a comprehensive approach for identifying components of a large protein complex and describes validation strategies to strengthen these observations obtained by classical proteomic strategies.
10.1126/science.286.5442.1153
86,443,876
For the identification of yeast genes specifying biochemical activities, a genomic strategy that is rapid, sensitive, and widely applicable was developed with an array of 6144 individual yeast strains, each containing a different yeast open reading frame (ORF) fused to glutathione S -transferase (GST). For the identifi...
10.1038/35048107
This paper describes a biochemical genomic approach in yeast by identifying enzymes using the yeast proteome fused to glutathione- S -transferase (GST).
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...
10.1038/35048107
This paper describes the first, small-scale, worm protein interaction map using the yeast two-hybrid system.
10.1073/pnas.97.3.1143
100,815,863
Protein–protein interactions play pivotal roles in various aspects of the structural and functional organization of the cell, and their complete description is indispensable to thorough understanding of the cell. As an approach toward this goal, here we report a comprehensive system to examine two-hybrid interactions i...
10.1038/35048107
References 51 and 52 describe large-scale protein interaction maps for yeast using the yeast two-hybrid system.
10.1073/pnas.94.26.14614
20,512,696
Insects respond to microbial infection by the rapid and transient expression of several genes encoding potent antimicrobial peptides. Herein we demonstrate that this antimicrobial response of Drosophila is not aspecific but can discriminate between various classes of microorganisms. We first observe that the genes enco...
10.1038/35100529
This study indicated that Drosophila can discriminate between different pathogen classes and induce an appropriate set of antimicrobial peptides.
10.4049/jimmunol.162.7.3749
139,017,330
Abstract The human homologue of Drosophila Toll (hToll), also called Toll-like receptor 4 (TLR4), is a recently cloned receptor of the IL-1/Toll receptor family. Interestingly, the TLR4 gene has been localized to the same region to which the Lps locus (endotoxin unresponsive gene locus) is mapped. To examine the role o...
10.1038/35100529
References 38–40 describe the first indication of TLR4 function in vivo
10.1084/jem.193.2.239
17,687,124
Although the essential role of tumor necrosis factor (TNF) in the control of intracellular bac-terial infection is well established, it is uncertain whether the related cytokines lymphotoxin-α (LTα3) and lymphotoxin-β (LTβ) have independent roles in this process. Using C57Bl/6 mice in which the genes for these cytokine...
10.1038/35095558
This paper elegantly shows the vital role of lymphotoxin-α in the formation and maintenance of tuberculous granulomas.
10.1126/science.276.5319.1684
41,103,965
In analyzing mechanisms of protection against intracellular infections, a series of human CD1-restricted T cell lines of two distinct phenotypes were derived. Both CD4 − CD8 − (double-negative) T cells and CD8 + T cells efficiently lysed macrophages infected with Mycobacterium tuberculosis . The cytotoxicity of CD4 − C...
10.1038/35095558
References 51 and 52 convincingly show the capacity of cytolytic T cells to directly curb mycobacterial growth.
10.1073/pnas.97.8.4204
61,050,312
A necessary role for cytotoxic T lymphocytes in protection against Mycobacterium tuberculosis (MTB) has been suggested by studies of the β2-microglobulin-deficient mouse, which is unable to present antigens through MHC class I and class I-like molecules and invariably succumbs early after infection. To identify the rel...
10.1038/35095558
References 56–58 not only underline the importance of MHC class I restricted CD8 + T cells in defence against tuberculosis, but also show the participation of other β 2 microglobulin-dependent mechanisms.
10.1073/pnas.96.22.12833
125,260,696
Tuberculosis is a chronic infectious disease that is transmitted by cough-propelled droplets that carry the etiologic bacterium, Mycobacterium tuberculosis. Although currently available drugs kill most isolates of M. tuberculosis , strains resistant to each of these have emerged, and multiply resistant strains are incr...
10.1038/35095558
This paper provides the first description of microarrays for the global analysis of tuberculosis.
10.1046/j.1365-2958.1999.01549.x
41,661,800
In 1993, the WHO declared tuberculosis a global emergency on the basis that there are 8 million new cases per year. The complete genome of the strain H37Rv of the causative microorganism, Mycobacterium tuberculosis , comprising 3924 genes has been sequenced. We compared the proteomes of two non‐virulent vaccine strains...
10.1038/35095558
The first description of the mycobacterial proteome provides a further means for the identification of antigens, virulence factors and so on.
10.1126/science.284.5419.1520
83,244,452
Bacille Calmette-Guérin (BCG) vaccines are live attenuated strains of Mycobacterium bovis administered to prevent tuberculosis. To better understand the differences between M. tuberculosis , M. bovis , and the various BCG daughter strains, their genomic compositions were studied by performing comparative hybridization...
10.1038/35095558
This paper used DNA microarray analysis to identify the genes lost in attenuation of BCG, providing a comprehensive list of genes that are absent in BCG and present in M. tuberculosis , which constitute potential candidate antigens for vaccination.
10.1073/pnas.250480397
103,506,683
Tuberculosis (TB) continues to ravage humanity, causing 2 million deaths per year. A vaccine against TB more potent than the current live vaccine, bacillus Calmette–Guérin (BCG), is desperately needed. Using two commercially available strains of BCG as host strains, BCG Connaught and Tice, we have constructed two recom...
10.1038/35095558
This paper describes the superior vaccine efficacy of a recombinant BCG that over expresses an antigen already present in wild-type BCG, and provides precedence for improving BCG as a novel vaccine candidate against tuberculosis.
10.1242/dev.126.9.1823
125,250,204
There are distinctive and characteristic genomic modifications in primordial germ cells that distinguish the germ cell lineage from somatic cells. These modifications include, genome-wide demethylation, erasure of allele-specific methylation associated with imprinted genes, and the re-activation of the X chromosome. Th...
10.1038/35047554
References 47 and 48 showed that germ cell nuclei, when transplanted to zygotes, had a characteristically restricted potential for development. This is explained, at least in part, by the erasure of imprints in primordial germ cells.
10.1101/gad.12.14.2108
58,400,635
DNA methylation patterns were evaluated during preimplantation mouse development by analyzing the binding of monoclonal antibody to 5-methylcytosine (5-MeC) on metaphase chromosomes. Specific chromosome patterns were observed in each cell stage. A banding pattern predominated in chromosomes at the one-cell stage. Bandi...
10.1038/35047554
References 58 – 62 showed that there is genome-wide demethylation in mouse preimplantation embryos followed by remethylation after implantation. The paternal genome is rapidly demethylated in the zygote, presumably by an active mechanism. The maternal genome is largely demethylated passively.
10.1101/gad.12.23.3693
67,356,832
Differentially methylated sequences associated with imprinted genes are proposed to control genomic imprinting. A 2-kb region located 5′ to the imprinted mouse H19 gene is hypermethylated on the inactive paternal allele throughout development. To determine whether this differentially methylated domain (DMD) is required...
10.1038/35047554
Deletion of the differentially methylated region upstream of H19 results in loss of repression of the linked Igf2 on the maternal allele, and loss of H19 methylation and silencing on the paternal allele.
10.1101/gad.6.10.1843
122,570,951
The mouse insulin-like growth factor II (Igf2) gene, which is located on distal chromosome 7 (Chr7), has been shown previously to undergo tissue-specific parental imprinting. This imprinting results in expression of Igf2 from the paternally inherited chromosome and repression of the maternally inherited allele in most ...
10.1038/35047554
The first description of a differentially methylated region (DMR1), located upstream of the Igf2 gene. This work also showed that the maternal Igf2 promoters, although repressed, were neither methylated nor in a closed chromatin conformation.
10.1242/dev.127.16.3419
82,974,944
The H19 imprinted gene is silenced when paternally inherited and active only when inherited maternally. This is thought to involve a cis-acting control region upstream of H19 that is responsible for regulating a number of functions including DNA methylation, asynchronous replication of parental chromosomes and an insul...
10.1038/35047554
Refs 85 – 87 describe silencers in the Igf2 and H19 genes that are important for the regulation of imprinting and expression. These silencers are tissue-specific and may interact with different sets of enhancers. Silencer function may depend on methylation or chromatin modification.
10.1523/jneurosci.08-10-03570.1988
102,006,145
Among other deficits, amygdalectomy impairs the ability of the animal to recognize the affective significance of a stimulus. In the present study, neuronal activity in the amygdala (AM) was recorded from alert monkeys while they performed tasks leading to the presentation of rewarding or aversive stimuli. Of 585 AM neu...
10.1038/35044563
A paper written by one of the few groups investigating neurons in the primate amygdala in relation to reward-related stimuli. They reported a number of different responses to the presentation of natural rewards.
10.1152/jn.2000.83.3.1677
32,841,132
Anatomic and behavioral evidence shows that TE and perirhinal cortices are two directly connected but distinct inferior temporal areas. Despite this distinctness, physiological properties of neurons in these two areas generally have been similar with neurons in both areas showing selectivity for complex visual patterns...
10.1038/35044563
The first demonstration of the prominent reward relationships in neurons of temporal cortex. Neuronal responses to task stimuli in the primate perirhinal cortex were profoundly affected by the distance to reward, whereas neuronal responses in the neighbouring TE area predominantly reflected the visual features of the s...
10.1126/science.282.5392.1335
103,660,470
Most natural actions are chosen voluntarily from many possible choices. An action is often chosen based on the reward that it is expected to produce. What kind of cellular activity in which area of the cerebral cortex is involved in selecting an action according to the expected reward value? Results of an analysis in m...
10.1038/35044563
Neurons in the primate cingulate motor area were active when animals switched to a different movement when continuing to perform the current movement would have produced less reward. This study is interesting from the point of view of movement selection and also for the influence of rewards on behavioural choices.
10.1101/gad.9.2.256
122,704,933
We have investigated the integration of sex- and tissue-specific transcriptional regulation in Drosophila. A single copy of the o-r enhancer from yolk protein genes directs female- and fat body-specific transcription. It consists of four protein-binding sites: dsxA, which binds male (DSXM) and female (DSXF) proteins en...
10.1038/35056032
Together with reference 37 , this paper shows that the two sex-specific isoforms of Dsx bind the same DNA site and have opposite effects on the transcription of the Yp1 yolk-protein gene.
10.1101/gad.834100
82,811,229
The only molecular similarity in sex determination found so far among phyla is between the Drosophila doublesex ( dsx ) and Caenorhabditis elegans mab-3 genes. dsx and mab-3 contain a zinc finger-like DNA-binding motif called the DM domain, perform several related regulatory functions, and are at least partially interc...
10.1038/35056032
A mouse knockout shows that Dmrt1 is required for postnatal testis differentiation, by affecting both Sertoli-cell and germ-cell development.
10.1002/bies.950170113
82,814,264
Abstract A hypothesis on the evolutionary origin of the genetic pathway of sex determination in the nematode Caenorhabditis elegans is presented here. It is suggested that the pathway arose in steps, driven by frequency‐dependent selection for the minority sex at each step, and involving the sequential acquisition of d...
10.1038/35056032
Proposes that sex-determining pathways, particularly those of nematodes, have evolved by the sequential addition of upstream regulators, so helping to explain the extreme molecular differences between these pathways and the evolution of the negatively acting Caenorhabditis elegans pathway.
10.1159/000055376
65,264,730
The <i>FHIT</i> gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumor suppressor gene involved in multiple tumors, including esophageal carcinoma. We analyzed Fhit expression using an immunohistochemical method in invasive carcinoma, carcinoma in situ (CIS) and dysplasia, in p...
10.1038/35101065
Provides an important clue that CIN might arise very soon after colorectal tumour initiation, leading to profound allelic losses even in very small adenomatous polyps.
10.1126/science.285.5426.418
62,042,906
A vertebrate securin (vSecurin) was identified on the basis of its biochemical analogy to the Pds1p protein of budding yeast and the Cut2p protein of fission yeast. The vSecurin protein bound to a vertebrate homolog of yeast separins Esp1p and Cut1p and was degraded by proteolysis mediated by an anaphase-promoting comp...
10.1038/35101065
Demonstration that human securin is identical to the pituitary tumour-transforming gene ( PTTG ), a candidate oncogene that is overexpressed in several cancer types.
10.1146/annurev.neuro.24.1.1041
122,555,394
▪ Abstract The developmental steps required to build a brain have been recognized as a distinctive sequence since the turn of the twentieth century. As marking tools for experimental embryology emerged, the cellular events of cortical histogenesis have been intensively scrutinized. On this rich backdrop, molecular gene...
10.1038/35097509
References 5–11 review research that addresses the developmental mechanisms underlying radial migration in normal and mutant cortex.
10.1242/dev.121.4.1029
125,241,754
Inactivation of the X-linked lacZ transgene provides a novel and powerful way of distinguishing between clonally related cellular populations in X inactivation mosaics. This ability to distinguish between clonal populations of cells in the mature cortex permits inferences to be made about cellular dispersion patterns d...
10.1038/35097509
Using X-inactivation mosaics, the studies described in references 27 and 28 provided evidence that some cortical neurons disperse tangentially in the cerebral cortex.
10.1126/science.278.5337.474
60,985,659
Although previous analyses indicate that neocortical neurons originate from the cortical proliferative zone, evidence suggests that a subpopulation of neocortical interneurons originates within the subcortical telencephalon. For example, γ-aminobutyric acid (GABA)–expressing cells migrate in vitro from the subcortical ...
10.1038/35097509
In addition to providing evidence for the existence of a tangential migration from the subpallium to the cortex, this is the first paper to show that cortical GABA interneurons originate in the subpallial telencephalon and that their development is largely dependent on Dlx genes.
10.1126/science.1061891
19,453,761
Most striatal and cortical interneurons arise from the basal telencephalon, later segregating to their respective targets. Here, we show that migrating cortical interneurons avoid entering the striatum because of a chemorepulsive signal composed at least in part of semaphorin 3A and semaphorin 3F. Migrating interneuron...
10.1038/35097509
Describes a novel mechanism that regulates the segregation of cortical and striatal interneurons during development, and identifies a role for neuropilin receptors in this process.
10.1242/dev.128.19.3759
104,392,914
Recent studies suggest that neurons born in the developing basal forebrain migrate long distances perpendicularly to radial glia and that many of these cells reach the developing neocortex. This form of tangential migration, however, has not been demonstrated in vivo, and the sites of origin, pathways of migration and ...
10.1038/35097509
References 44 and 45 provide the first clear evidence that cells derived from the subpallium ultimately constitute a stable population of interneurons in the adult cortex.
10.1126/science.8178174
123,166,713
During the development of the mammalian brain, neuronal precursors migrate to their final destination from their site of birth in the ventricular and subventricular zones (VZ and SVZ, respectively). SVZ cells in the walls of the lateral ventricle continue to proliferate in the brain of adult mice and can generate neuro...
10.1038/35097509
Using different approaches, references 56 and 57 first showed a migratory pathway from the anterior SVZ to the olfactory bulb.
10.1242/dev.128.3.353
41,741,588
Recent evidence suggests that projection neurons and interneurons of the cerebral cortex are generally derived from distinct proliferative zones. Cortical projection neurons originate from the cortical ventricular zone (VZ), and then migrate radially into the cortical mantle, whereas most cortical interneurons originat...
10.1038/35097509
The first paper to show that cells derived from distinct progenitor zones in the subpallium follow spatially and temporally different routes in their migration to the cortex. With reference 41 , provided evidence that different cortical interneuron subclasses come from different progenitor domains.
10.1242/dev.128.2.193
62,235,242
The telencephalon has two major subdivisions, the pallium and subpallium. The pallium, which primarily consists of glutamatergic cortical structures, expresses dorsal molecular markers, whereas the subpallium, which primarily consists of the GABAergic basal ganglia, expresses ventral molecular markers. Here, we present...
10.1038/35097509
Together with reference 38 , references 66–69 describe the role of several transcription factors in the establishment of different progenitor zones in the telencephalon.
10.1242/dev.128.22.4635
104,393,951
Cortical nonpyramidal cells, the GABA-containing interneurons, originate mostly in the medial ganglionic eminence of the ventral telencephalon and follow tangential migratory routes to reach the dorsal telencephalon. Although several genes that play a role in this migration have been identified, the underlying cellular...
10.1038/35097509
Indicates a role for the adhesion molecule TAG-1 in regulating the migration of tangentially migrating neurons in the telencephalon.
10.1126/science.271.5251.978
104,311,583
In the brain of adult mice, cells that divide in the subventricular zone of the lateral ventricle migrate up to 5 millimeters to the olfactory bulb where they differentiate into neurons. These migrating cells were found to move as chains through a well-defined pathway, the rostral migratory stream. Electron microscopic...
10.1038/35097509
Identifies a new mechanism of neuronal migration in the telencephalon.
10.1128/mcb.16.8.4555
28,217,273
Recent studies showing a correlation between the levels of DNA (cytosine-5-)-methyltransferase (DNA MTase) enzyme activity and tumorigenicity have implicated this enzyme in the carcinogenic process. Moreover, hypermethylation of CpG island-containing promoters is associated with the inactivation of genes important to t...
10.1038/35049533
This paper uniquely describes the use of somatic cell knockout technology to delete the DNMT1 gene in a cancer cell line.
10.1126/science.252.5009.1097
60,789,945
The fragile X syndrome, a common cause of inherited mental retardation, is characterized by an unusual mode of inheritance. Phenotypic expression has been linked to abnormal cytosine methylation of a single CpG island, at or very near the fragile site. Probes adjacent to this island detected very localized DNA rearrang...
10.1038/35049533
References 94 and 95 were among the first to show that lack of expression of the FMR1 gene was associated with abnormal expansion and methylation of a trinucleotide repeat.
10.1093/oso/9780198505013.001.0001
149,187,966
Abstract The amygdala is a central component of the limbic brain system and is known to be vital to understanding aspects of emotion, memory and social behaviour. Dysfunction of the structure is also thought to contribute to a variety of disorders, including autism, Alzheimer's Disease and schizophrenia. The nature of ...
10.1038/35072584
Book that includes several detailed reviews on the role of the amygdala in emotion.
10.1146/annurev.neuro.23.1.155
41,767,235
The field of neuroscience has, after a long period of looking the other way, again embraced emotion as an important research area. Much of the progress has come from studies of fear, and especially fear conditioning. This work has pinpointed the amygdala as an important component of the system involved in the acquisiti...
10.1038/35072584
A recent review of the role of the amygdala in fear conditioning.
10.1242/jcs.112.21.3603
104,416,064
Metalloprotease-disintegrins (ADAMs) have captured our attention as key players in fertilization and in the processing of the ectodomains of proteins such as tumor necrosis factor (α) (TNF(α)), and because of their roles in Notch-mediated signaling, neurogenesis and muscle fusion. ADAMs are integral membrane glycoprote...
10.1038/35081571
Excellent review that introduces the biology of ADAMs and then provides details on two members relevant to the CNS: ADAM10 and -17.
10.1002/ana.410400606
82,394,705
Abstract Treatment with interferon beta‐1b has substantial clinical benefit in the demyelinating disease multiple sclerosis, yet the mechanism of action in the disease remains largely unknown. Gelatinase A (matrix metalloproteinase‐2, 72‐kd gelatinase) and B (matrix metalloproteinase‐9, 92‐kd gelatinase) are matrix met...
10.1038/35081571
References 33 and 34 describe a key role of interferon-β in MS: the alteration of MMP production by leukocytes.
10.1126/science.289.5482.1202
107,263,946
Tissue degradation by the matrix metalloproteinase gelatinase A is pivotal to inflammation and metastases. Recognizing the catalytic importance of substrate-binding exosites outside the catalytic domain, we screened for extracellular substrates using the gelatinase A hemopexin domain as bait in the yeast two-hybrid sys...
10.1038/35081571
A novel role for MMPs was revealed by this report. The interaction of MMP2 with a chemokine — MCP3 — converted the MCP3 into an antagonist at several chemokine receptors, thereby abolishing a directional cue for the migration of leukocytes.
10.1126/science.290.5498.1965
122,990,006
Tissue manipulation experiments in amphibians more than 50 years ago showed that induction of the inner ear requires two signals: a mesodermal signal followed by a neural signal. However, the molecules mediating this process have remained elusive. We present evidence for mesodermal initiation of otic development in hig...
10.1038/35097549
A series of experiments defining the tissue interactions that underlie induction of the inner ear in chick, and the demonstration that two growth factors/signalling molecules, FGF19 and WNT8C, act synergistically to mediate the tissue interactions.
10.1073/pnas.071586298
40,208,092
Eye development in both invertebrates and vertebrates is regulated by a network of highly conserved transcription factors. However, it is not known what controls the expression of these factors to regulate early eye formation and whether transmembrane signaling events are involved. Here we establish a role for signalin...
10.1038/35097549
This paper presents the extraordinary finding that a single transmembrane receptor (frizzled 3) for a signalling molecule, when overexpressed, results in the formation of a complex structure (the eye), and that expression of a dominant-negative form of this receptor on one side of the embryo completely blocks eye forma...
10.1101/gad.831700
122,860,449
Cytoplasmic polyadenylation element binding (CPEB) proteins bind to and regulate the translation of specific mRNAs. CPEBs from Xenopus, Drosophila , and Spisula participate in oogenesis. In this report, we examine the biological roles of all identifiable CPEB homologs in a single organism, Caenorhabditis elegans . We f...
10.1038/35080081
The authors describe four CPEB homologues in C. elegans cpb-1 cpb-2 cpb-3 and fog-1 . RNA interference assays show that CPB-1 and FOG-1 have key functions in spermatogenesis whereas none seems to be required for oogenesis.
10.1073/pnas.95.9.5323
124,388,090
The nature of information stemming from a single neuron and conveyed simultaneously to several hundred target neurons is not known. Triple and quadruple neuron recordings revealed that each synaptic connection established by neocortical pyramidal neurons is potentially unique. Specifically, synaptic connections onto th...
10.1038/35049047
References 20 and 21 were the first direct demonstration that transmitter release could be differentially and simultaneously modulated at individual terminals from the same axon.
10.1128/jvi.65.11.6292-6295.1991
62,565,879
We established that follicular dendritic cells (FDCs) are the site of abnormal prion protein (PrPCJD) accumulations in lymphoid tissues from mice infected with Creutzfeldt-Jakob disease. Evidence of positive FDC staining was observed in Creutzfeldt-Jakob disease-infected mice irrespective of the inoculation route, whil...
10.1038/35052063
This paper showed that FDCs accumulate disease-associated prion protein, and kick-started the whole field of prion neural immunology.
10.1126/science.289.5479.595
38,581,692
Starting with purified, bacterially produced protein, we have created a [ PSI + ]-inducing agent based on an altered (prion) conformation of the yeast Sup35 protein. After converting Sup35p to its prion conformation in vitro, we introduced it into the cytoplasm of living yeast using a liposome transformation protocol. ...
10.1038/35052063
In this paper, yeast geneticists have achieved what continues to be a Holy Grail for mammalian prion science: de novo generation of recombinant, infectious prions.
10.1093/oso/9780198547815.001.0001
148,980,519
Abstract The genetic code was deciphered experimentally around 1966 and for a number of years scientists considered it to be "universal" for all forms of life. In 1981 researchers shocked the scientific community with the discovery that the code differed in mitochondria and certain other organisms, evidence that the ge...
10.1038/35047500
Exposition of the 'codon capture' hypothesis, which proposes a neutral mechanism for codon reassignment through a stage in which the codon disappears from the genome entirely.
10.1046/j.1365-2958.1999.01233.x
105,404,443
Several species of the genus Candida decode the standard leucine CUG codon as serine. This and other deviations from the standard genetic code in both nuclear and mitochondrial genomes invalidate the notion that the genetic code is frozen and universal and prompt the questions ‘why alternative genetic codes evolved and...
10.1038/35047500
Provides experimental support for the idea that ambiguous decoding can be advantageous in some circumstances.
10.1139/o95-086
58,603,434
Our thesis is that the characteristics of the translational machinery and its organization are selected in part by evolutionary pressure on genomic traits have nothing to do with translation per se. These genomic traits include size, composition, and architecture. To illustrate this point, we draw parallels between the...
10.1038/35047500
Most complete exposition of the 'genome reduction' hypothesis, which suggests that pressure to minimize mitochondrial genomes leads to the reassignment of specific codons.
10.1126/science.279.5357.1665
16,751,706
The transfer RNA (tRNA) multigene family comprises 20 amino acid–accepting groups, many of which contain isoacceptors. The addition of isoacceptors to the tRNA repertoire was critical to establishing the genetic code, yet the origin of isoacceptors remains largely unexplored. A model of tRNA evolution, termed “tRNA gen...
10.1038/35047500
Demonstration that a single-base change at the anticodon of a tRNA can change both its decoding and aminoacylation specificities. This paper has important implications for the use of tRNA phylogeny to track the evolution of the genetic code.
10.1126/science.1058040
83,455,108
A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasm...
10.1038/35103535
References 1 and 2 report the frequency, distribution and features of single nucleotide variation from a whole-genome perspective, based on the results from the Human Genome Project and from Celera Genomics.
10.1126/science.2999980
62,075,261
Two new methods were used to establish a rapid and highly sensitive prenatal diagnostic test for sickle cell anemia. The first involves the primer-mediated enzymatic amplification of specific β-globin target sequences in genomic DNA, resulting in the exponential increase (220,000 times) of target DNA copies. In the sec...
10.1038/35103535
References 25 and 26 are classic papers that contain the original descriptions of the polymerase chain reaction. PCR has changed the way human genetics is conducted and is the technology that allows detection of SNPs in the human genome.
10.1126/science.3413476
61,249,782
An assay for the presence of given DNA sequences has been developed, based on the ability of two oligonucleotides to anneal immediately adjacent to each other on a complementary target DNA molecule. The two oligonucleotides are then joined covalently by the action of a DNA ligase, provided that the nucleotides at the j...
10.1038/35103535
A landmark paper in the SNP field because it is the first to show the value of an enzyme as a tool for genotyping SNPs. This study introduces the oligonucleotide ligation assay.
10.1101/gr.8.12.1245
50,147,054
Mutational analysis of large genes with complex genomic structures plays an important role in medical genetics. Technical limitations associated with current mutation screening protocols have placed increased emphasis on the development of new technologies to simplify these procedures. High-density arrays of >90,000...
10.1038/35103535
A thorough article that presents a useful strategy for designing functional multiplex PCR panels. This study is also one of the early applications of high-density GeneChip microarrays for SNP detection and genotyping.
10.1101/gr.10.7.1031
17,595,690
This study describes a practical system that allows high-throughput genotyping of single nucleotide polymorphisms (SNPs) and detection of mutations by allele-specific extension on primer arrays. The method relies on the sequence-specific extension of two immobilized allele-specific primers that differ at their 3′-nucle...
10.1038/35103535
Description of allele-specific primer extension on microarrays for multiplex SNP genotyping. The paper presents an 'array of arrays' format for microscope slides that is of general use for high-throughput genotyping.
10.1101/gr.10.4.549
59,701,022
A rapid, high throughput readout for single-nucleotide polymorphism (SNP) analysis was developed employing single base chain extension and cytometric analysis of an array of fluorescent microspheres. An array of fluorescent microspheres was coupled with uniquely identifying sequences, termed complementary ZipCodes (cZi...
10.1038/35103535
A clear presentation of the concept of generic 'tag' sequences as applied to SNP genotyping.
10.1101/gr.9.5.492
133,844,411
A new method for DNA diagnostics based on template-directed primer extension and detection by fluorescence polarization is described. In this method, amplified genomic DNA containing a polymorphic locus is incubated with oligonucleotide primers (designed to hybridize to the DNA template adjacent to the polymorphic site...
10.1038/35103535
A good description of fluorescence polarization as a detection method in homogeneous SNP assays.
10.1002/anie.201309399
103,777,403
Abstract Aryl sulfonyl chlorides (e.g. Ts‐Cl) are beloved of organic chemists as the most commonly used S VI electrophiles, and the parent sulfuryl chloride, O 2 S VI Cl 2 , has also been relied on to create sulfates and sulfamides. However, the desired halide substitution event is often defeated by destruction of the ...
10.1038/s43586-021-00028-z
This article presents an initial description of SuFEx chemistry as an efficient biocompatible click chemistry tool
10.1126/science.7973629
125,074,660
A simple technique has been devised that allows the direct synthesis of native backbone proteins of moderate size. Chemoselective reaction of two unprotected peptide segments gives an initial thioester-linked species. Spontaneous rearrangement of this transient intermediate yields a full-length product with a native pe...
10.1038/s43586-021-00028-z
This article presents an initial description of native chemical ligation, which enabled the use of fully deprotected peptides through bioorthogonal reaction of a thioester motif with an N-terminal cysteine residue
10.1073/pnas.95.12.6705
84,466,244
A protein semisynthesis method—expressed protein ligation—is described that involves the chemoselective addition of a peptide to a recombinant protein. This method was used to ligate a phosphotyrosine peptide to the C terminus of the protein tyrosine kinase C-terminal Src kinase (Csk). By intercepting a thioester gener...
10.1038/s43586-021-00028-z
This article presents the first description of expressed protein ligation — the application of native chemical ligation to ligate small synthetic sequences to much larger recombinant protein fragments
10.1126/science.287.5460.2007
104,066,814
Selective chemical reactions enacted within a cellular environment can be powerful tools for elucidating biological processes or engineering novel interactions. A chemical transformation that permits the selective formation of covalent adducts among richly functionalized biopolymers within a cellular context is present...
10.1038/s43586-021-00028-z
This article presents the first description of cell surface engineering using azido reporters and bioorthogonal chemistry
10.1073/pnas.0911116107
104,088,350
Chemical reactions that enable selective biomolecule labeling in living organisms offer a means to probe biological processes in vivo. Very few reactions possess the requisite bioorthogonality, and, among these, only the Staudinger ligation between azides and triarylphosphines has been employed for direct covalent modi...
10.1038/s43586-021-00028-z
This article compares several copper-free chemistries for metabolic labelling in mice
10.1146/annurev-genom-121520-081242
121,679,175
Somatic mutations arise postzygotically, producing genetic differences between cells in an organism. Well established as a driver of cancer, somatic mutations also exist in nonneoplastic cells, including in the brain. Technological advances in nucleic acid sequencing have enabled recent breakthroughs that illuminate th...
10.1038/s43587-022-00264-2
A Review article that presents the somatic mutational burden in aging and diseased brain cells.
10.1002/em.22087
83,433,562
Living organisms are continuously exposed to a myriad of DNA damaging agents that can impact health and modulate disease‐states. However, robust DNA repair and damage‐bypass mechanisms faithfully protect the DNA by either removing or tolerating the damage to ensure an overall survival. Deviations in this fine‐tuning ar...
10.1038/s43587-022-00264-2
A Review article that presents various DNA damage and repair pathways.
10.1177/1745691615568999
20,859,869
Most people have experienced loneliness and have been able to overcome it to reconnect with other people. In the current review, we provide a life-span perspective on one component of the evolutionary theory of loneliness—a component we refer to as the reaffiliation motive (RAM). The RAM represents the motivation to re...
10.1038/s44159-022-00124-1
This article reviews and expands the evolutionary theory of loneliness and reviews empirical findings on the development of loneliness across the life span
10.1093/geronb/gby153
121,865,295
Abstract Objectives Partnership status is a central predictor of loneliness. The strength of this predictive relationship, however, may decrease in the course of aging and over historical time. Moreover, there may be aging-related and historical changes in the satisfaction with partnership and singlehood. Method Longit...
10.1038/s44159-022-00124-1
This exemplary empirical study used an elegant design to examine how historical shifts in social norms affect the link between partnership status and loneliness
10.1177/1745691617713052
83,506,922
With the rise of online social networking, social relationships are increasingly developed and maintained in a digital domain. Drawing conclusions about the impact of the digital world on loneliness is difficult because there are contradictory findings, and cross-sectional studies dominate the literature, making causat...
10.1038/s44159-022-00124-1
This is a comprehensive and nuanced review on the link between social media use and loneliness
10.1177/1089268020959033
102,991,320
Loneliness is a common experience with major negative consequences for well-being. Although much research has examined protective and risk factors for loneliness, we know little about its cultural underpinnings. The few studies that exist seem paradoxical, suggesting that loneliness is higher in cultures where tighter ...
10.1038/s44159-022-00124-1
This theoretical article introduces the culture–loneliness framework to explain national differences in loneliness
10.1177/0956797619836102
82,636,365
In this study, we investigated associations between the characteristics of the neighborhoods in which young adults live and their feelings of loneliness, using data from different sources. Participants were drawn from the Environmental Risk Longitudinal Twin Study. Loneliness was measured via self-reports at ages 12 an...
10.1038/s44159-022-00124-1
This is an exemplary study on the role of neighbourhood characteristics in explaining geographical differences in loneliness
10.1177/1088868310377394
41,765,814
Social and demographic trends are placing an increasing number of adults at risk for loneliness, an established risk factor for physical and mental illness. The growing costs of loneliness have led to a number of loneliness reduction interventions. Qualitative reviews have identified four primary intervention strategie...
10.1038/s44159-022-00124-1
This is a comprehensive meta-analysis on loneliness interventions, with a particular focus on which characteristics of interventions are linked to a greater efficacy
10.1126/sciadv.aaw9867
123,184,967
The band inversion in topological phase matters bring exotic physical properties such as the topologically protected surface states (TSS). They strongly influence the surface electronic structures of the materials and could serve as a good platform to gain insight into the surface reactions. Here we synthesized high-qu...
10.1038/s42254-022-00477-9
This work proposed the use of bulk single crystals to detect the influence of TSSs on catalysis reactions.
10.1073/pnas.1115555109
39,844,957
The physical property investigation (like transport measurements) and ultimate application of the topological insulators usually involve surfaces that are exposed to ambient environment (1 atm and room temperature). One critical issue is how the topological surface state will behave under such ambient conditions. We re...
10.1038/s42254-022-00477-9
This work tracks the evolution of TSSs under surface reconstruction and adsorption and reveals the robustness of the TSSs
10.1111/j.1365-2486.2010.02279.x
41,500,144
Abstract Accurate inventory of tropical peatland is important in order to (a) determine the magnitude of the carbon pool; (b) estimate the scale of transfers of peat‐derived greenhouse gases to the atmosphere resulting from land use change; and (c) support carbon emissions reduction policies. We review available inform...
10.1038/s43017-022-00289-6
This is a comprehensive assessment of the extent, volume and carbon stocks of peatlands across the tropics, highlighting their importance in the global carbon cycle and key uncertainties
10.1088/1748-9326/abb853
100,603,597
Abstract Tropical peatlands in Southeast Asia cover ∼25 million hectares and exert a strong influence on the global carbon cycle. Recent widespread peatland subsidence and carbon dioxide emissions in response to human activity and climate change have been well documented, but peatland genesis remains poorly understood....
10.1038/s43017-022-00289-6
This study compares the development of coastal and inland peatlands in West Kalimantan, Indonesia, and provides a description of the oldest known peat deposit in Southeast Asia
10.1002/2016gl072245
19,641,657
Abstract Tropical peatlands are an important global carbon (C) store but are threatened by drainage for palm oil and wood pulp production. The store's stability depends on the dynamics of the peatland water table, which in turn depend on peat permeability. We found that an example of the most abundant type of tropical ...
10.1038/s43017-022-00289-6
This study finds that the permeability of ombrotrophic tropical peat is higher than expected, resulting in deep water tables in ditched tropical peatlands and associated high rates of peat oxidation
10.1111/gcb.13422
125,047,473
Abstract Pristine tropical peat swamp forests ( PSF s) represent a unique wetland ecosystem of distinctive hydrology which support unique biodiversity and globally significant stores of soil carbon. Yet in Indonesia and Malaysia, home to 56% of the world's tropical peatland, they are subject to considerable development...
10.1038/s43017-022-00289-6
This study reviews the ecosystem services provided by Southeast Asian peatlands and discusses key policy challenges for peatland management