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At least 1,693 records · Page 94Linked to original sources
PubMed1997

Mash1 and neurogenin1 expression patterns define complementary domains of neuroepithelium in the developing CNS and are correlated with regions expressing notch ligands.

Genetic studies in Drosophila and in vertebrates have implicated basic helix-loop-helix (bHLH) genes in neuronal fate determination and cell type specification. We have compared directly the expression of Mash1 and neurogenin1 (ngn1), two bHLH genes that are expressed specifically at early stages of neurogenesis. In the PNS these genes are expressed in complementary autonomic and sensory lineages. In the CNS in situ hybridization to serial sections and double-labeling experiments indicate that Mash1 and ngn1 are expressed in adjacent and nonoverlapping regions of the neuroepithelium that correspond to future functionally distinct areas of the brain. We also showed that in the PNS several other bHLH genes exhibit similar lineal restriction, as do ngn1 and Mash1, suggesting that complementary cascades of bHLH factors are involved in PNS development. Finally, we found that there is a close association between expression of ngn1 and Mash1 and that of two Notch ligands. These observations suggest a basic plan for vertebrate neurogenesis whereby regionalization of the neuroepithelium is followed by activation of a relatively small number of bHLH genes, which are used repeatedly in complementary domains to promote neural determination and differentiation.

Animals↗
PubMed1997

Role of suppressor of hairless in the delta-activated Notch signaling pathway.

The Notch protein (N) acts as a transmembrane receptor for intercellular signals controlling cell fate choices in vertebrates and invertebrates. Genetical and molecular evidence indicates that, during Drosophila neurogenesis, an evolutionarily conserved transcription factor, Suppressor of Hairless [Su(H)], transduces the signal of N activation by its ligand Delta (D1). Su(H) plays a direct role in the immediate response of the genome to N signaling by up-regulating the transcription of the Enhancer of split Complex [E(spl)-C] genes. These findings suggest that the N transduction pathway can be described as a simple, linear cascade of molecular activation. At the molecular level, the mechanism of Su(H) "activation" is yet unknown. Two non-exclusive models have been proposed. In the first one, Su(H) binds to inactive N at the membrane. The binding of D1 to N in the extracellular space somehow interferes with the N-mediated cytoplasmic retention of Su(H), resulting in the nuclear translocation and "activation" of Su(H). In the second model, DNA-bound Su(H) is proposed to be "activated" in the nucleus by the direct binding of a processed form of N, acting as a transcriptional coactivator. This nuclear N protein would be generated by the ligand-induced proteolytic cleavage of the N transmembrane receptor.

Animals↗
PubMed2005

Expression of a novel zebrafish zinc finger gene, gli2b, is affected in Hedgehog and Notch signaling related mutants during embryonic development.

Gli zinc-finger proteins are known as downstream mediators of the evolutionary conserved Hedgehog pathway. In zebrafish, gli2 functions differently from Gli2 in mammals. This difference could be due to the gli2 duplication in teleosts evolution and partial redundancy between two duplicated genes. Here, we report a novel zebrafish gli2-like cDNA. Its structure, genetic location, and distinct expression pattern in the central nervous system suggested that this gene might represent a second gli2 of teleosts, and we named it gli2b. gli2b was expressed in the neural keel, excluding the forebrain-midbrain boundary, while gli2 expression complemented this pattern. After 24 hours postfertilization, several specific domains of gli2b expression were observed in the lateral and medial hindbrain and hypothalamus. In mutants affecting the Hedgehog and Notch signaling pathways, gli2b expression was either disrupted or extended in different regions.

Amino Acid Sequence↗
PubMed2026

NOTCH3 Internal Tandem Duplication Defines a Novel Oncogenic Activation Mechanism of NOTCH Signaling.

NOTCH signaling is activated in tumors through multiple mechanisms, including mutations, gene rearrangements, and gene amplification. We report a novel activation mechanism, an internal tandem duplication (ITD) near the NOTCH3 negative regulatory region (NRR), found in a myogenic mesenchymal neoplasm. This 17-amino acid residue duplication disrupts the tightly autoinhibited structure surrounding the S2 cleavage site, resulting in ligand-independent S2 cleavage and constitutive pathway activation, as demonstrated by increased expression of the NOTCH3 target gene HES1. Cells expressing NOTCH3-ITD showed increased nuclear localization of the receptor and exhibited malignant phenotypes, including enhanced proliferation and migration. Together, these findings support the oncogenic role of NOTCH3-ITD.

Receptor, Notch3↗
PubMed2005

Notch 1 interacts with the amyloid precursor protein in a Numb-independent manner.

We hypothesized that the physical interaction between the amyloid precursor protein (APP) and Notch 1 (N1) may be mediating the reported cross-talk between the respective signaling pathways. Immunoprecipitation of mouse N1 (mN1) or extracellular domain truncated mN1 (mN1-TM, mimics TACE-produced membrane-bound C-terminal fragment) specifically coprecipitated APP(751). Conversely, immunoprecipitation of APP(751) specifically coprecipitated mN1, furin-generated membrane-bound mN1 C-terminal fragment (f.mN1-TM), or mN1-TM. The London mutation of APP did not affect the APP(751)/mN1 interaction. Coexpression of APP(751) and mN1 did not affect APP processing or production of mN1 intracellular domain (mNICD). The APP(751)/mN1 interaction was Numb-independent, insofar as it was observed in HEK293 cells that lack detectable levels of Numb and was unaffected by the expression of exogenous Numb or deletion of the APP cytoplasmic domain, including the Numb-binding YENPTY sequence. This interaction was unaffected even when the N-terminal 647 amino acids of APP were replaced by a sequence of secreted alkaline phosphatase. These data combined with data showing interaction between mN1-TM and APP(751) suggest that their transmebrane domains and short sequences around them are sufficient for the interaction and that APP(751) and mN1 interact in cis. Our results imply novel functions of APP and/or N1 that derive from their interaction.

Alzheimer Disease↗
PubMed1998

DBI-1, a novel gene related to the notch family, modulates mitogenic response to insulin-like growth factor 1.

The insulin-like growth factor 1 (IGF-1) receptor has been found to transform fibroblast cells when overexpressed. The removal of 108 aa from the C-terminus of the IGF-1 receptor abolishes the transforming ability of the receptor without affecting its ability to induce cell growth. The availability of this mutant receptor provides a means to examine the changes in gene expression which take place during transformation, solely in response to an increased number of IGF-1 receptors. Using differential display, we have examined differences in gene expression between cells expressing a wild-type, transforming IGF-1 receptor and cells expressing a C-terminally truncated, nontransforming IGF-1 receptor. We have cloned a novel 6. 3-kb cDNA transcript (DBI-1) which is expressed at much lower levels in cells containing the wild-type IGF-1 receptor. The predicted protein sequence of DBI-1 contains seven EGF-like repeats, which bear >90% sequence identity to the rat Notch 2 protein. The cDNA also contains a potential DEAD box in the C-terminal region. The DBI-1 message is detected at relatively high levels in cardiac tissue and at lower levels in lung, liver, and kidney. Antibodies generated to a unique region of the DBI-1 protein recognize a protein of 88 kDa, which is localized in the nucleus. Overexpression of DBI-1 in cells which contain the wild-type IGF-1 receptor diminishes the mitogenic response to IGF-1.

3T3 Cells↗
PubMed1991

Nerve cells of Drosophila Notch mutant are differentiated inside amphibian brain: a new approach for the analysis of genetic control of nerve cell differentiation.

Fragments of the neural primordium of a new Notch mutant of Drosophila melanogaster produced in our laboratory were transplanted into the neural tube of embryos of 4 amphibian species (caudate and ecaudate) immediately after completion of neurulation. The grafts were identified by using a light microscope, scanning electron miscroscope, and in situ hybridization with mobile genetic elements of Drosophila and fluorescent dyes as markers. As has been shown, Drosophila nerve cells survive and differentiate inside the neural tube of amphibian embryos. The grafts increase in size by twentyfold and the cell proliferation zones are retained during the period of six months. Differentiated cells of the graft formed axon-dendritic contacts with recipient cells and penetrated into the organisms' brain structures. The effect of Drosophila transplants proved to be different for caudate and ecaudate amphibians. The presence of the graft accelerated the development of Xenopus laevis and it also affected their behavior. This approach can be very useful for the study of genetic basis of development and behavior.

Animals↗
PubMed1987

The femoral head notch.

A notch-like defect at the vertex of the proximal femoral ossification center is a normal variant in children. This has often been mistaken for Legg-Perthes disease. This sharply defined defect is distinct from the irregular epiphyseal ossification patterns common in other areas.

Child↗
PubMed1985

The upper femoral notch.

A notch-like defect in the cortex of the medial side of the femoral neck is described in asymptomatic children. Its appearance is similar to the metaphyseal cortical defects seen in other locations as normal variants.

Child↗
PubMed1992

MRI demonstration of Kernohan's notch: case report.

We report a left acute subdural haematoma caused by rupture of a left anterior cerebral artery aneurysm, which progressed to left hemiparesis. Coronal MRI was superior to CT for visualizing Kernohan's notch.

Acute Disease↗
PubMed1999

A fast recursive-least-squares adaptive notch filter and its applications to biomedical signals.

A fast recursive-least-squares (FRLS) adaptive notch filter (ANF) for cancellation of sinusoidal interference from recorded biomedical signals is investigated. The FRLS ANF is derived by making an approximation to the conventional recursive-least-squares (RLS) ANF for computation economy. It outperforms the commonly adopted least-mean-squares (LMS) ANF, demonstrating a rapid and bandwidth-insensitive initial convergence. A novel application of the FRLS ANF is for the elimination of the tonal artefact in distortion product otoacoustic emission (DPOAE) signals.

Electronics, Medical↗
PubMed2000

[The "empty" cruciate ligament notch. Aplasia or trauma aftereffect?].

Discoligamentary injuries of the knee frequently lead to an arthroscopic inspection of the joint. We present a case in which after two traumatic events a mensal tear and an empty notch were found on arthroscopic examination. The differential diagnosis of congenital aplasia of the anterior cruciate ligament (CAACL) versus neglected rupture of the ACL is discussed.

Adolescent↗
PubMed1999

Correlation of the intercondylar notch width of the femur to the width of the anterior and posterior cruciate ligaments.

The purpose of this study was to determine if a correlation exists between the intercondylar notch width (NW) of the femur and the width of the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL). A study group of 124 consecutive patients (mean age 36.6 +/- 15.2 years; 67 men, 57 women) underwent a magnetic resonance imaging evaluation for knee pain but did not have an ACL or PCL tear or arthrosis. A T2 weighted coronal cut was identified and was located at the middle of the tibial spine, which represented the plane where the ACL and PCL cross each other when the knee is in 10 degrees of flexion. The NW and the width of the ACL and PCL were measured at the level of the middle of the popliteal hiatus on a physician-independent console that allowed for digital measurements in millimeters. Our results showed a statistically significant correlation between NW and ACL width (r = 0.87; P < 0.001) and between NW and PCL width (r = 0.75; P < 0.001). The mean ACL width was 6.4 +/- 1.4 mm (range 3-10 mm). The mean PCL width was 10.2 +/- 2.0 mm (range 6-17 mm). The mean ACL width was 5.7 +/- 1.1 mm for women and 7.1 +/- 1.2 mm for men (P < 0.001). The mean PCL width was 9.5 +/- 1.7 mm for women and 10.9 +/- 2.0 for men (P < 0.001). Our results indicate that NW correlates with ACL and PCL width. In addition, ACL and PCL widths are narrower in women than men.

Adolescent↗
PubMed2002

A beaklike bony extension of the medial aspect of the greater sciatic notch: a radiographic appearance sexually influenced.

The bony pelvis provides more obvious sex differences than any other bone in the human skeleton. This study evaluates a bony extension of the medial aspect of the greater sciatic notch, which extends caudad to the arcuate line as seen on pelvic radiographs. A total of 2620 randomly selected supine pelvic radiographs (anteroposterior view) of adult females and males were reviewed. The subjects belonged to a central Anatolian population and their age ranged between 18 and 77 years in females and between 18 and 81 years in males. Only 22 (1.7%) of the 1337 female pelvic radiographs showed a bony extension, whereas 882 (68.8%) of the males had one. All these bony extensions were bilateral and symmetric. The results were statistically significant (P < 0.001). We assert that this radiographic appearance is a male characteristic.

Adolescent↗
PubMed2004

Fetal intra-abdominal umbilical vein dilatation associated with notching in umbilical artery.

INTRODUCTION: Dilatation of the fetal intra-abdominal umbilical vein is a rare entity. It is unclear whether prenatally diagnosed umbilical vein dilatation is associated with an increased risk of fetal anomalies or poor perinatal outcome. Umbilical artery waveform notching may be a predictor of cord abnormalities. It seems reasonable following the baby closely after the diagnosis of both conditions. CASE REPORT AND DISCUSSION: We present here a new case diagnosed by ultrasonography at 30 weeks of gestation with normal fetal outcome and discuss the clinical features and the management of these rare abnormalities.

Adult↗
PubMed1979

Mid systolic notching of the pulmonary valve in the absence of pulmonary hypertension.

In a patient with idiopathic dilatation of the pulmonary artery the pulmonary valve echogram showed a prominent mid systolic closing motion or notching indistinguishable from that seen in pulmonary hypertension. Normal right ventricular and pulmonary arterial pressures were recorded simultaneously with echocardiograms of the pulmonary valve.

Adult↗
PubMed1991

TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms.

Previously we described joining of DNA in the beta T cell receptor gene to DNA of an uncharacterized locus in a t(7;9)(q34;q34.3) chromosomal translocation from a case of human T lymphoblastic leukemia (T-ALL). We now show that the locus on chromosome 9 contains a gene highly homologous to the Drosophila gene Notch. Transcripts of the human gene, for which we propose the name TAN-1, and its murine counterpart are present in many normal human fetal and adult mouse tissues, but are most abundant in lymphoid tissues. In t(7;9)(q34;q34.3) translocations from three cases of T-ALL, the breakpoints occur within 100 bp of an intron in TAN-1, resulting in truncation of TAN-1 transcripts. These observations suggest that TAN-1 may be important for normal lymphocyte function and that alteration of TAN-1 may play a role in the pathogenesis of some T cell neoplasms.

Amino Acid Sequence↗