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Expression pattern of Motch, a mouse homolog of Drosophila Notch, suggests an important role in early postimplantation mouse development.

The Notch gene of Drosophila encodes a large transmembrane protein involved in cell-cell interactions and cell fate decisions in the Drosophila embryo. To determine if a gene homologous to Drosophila Notch plays a role in early mouse development, we screened a mouse embryo cDNA library with probes from the Xenopus Notch homolog, Xotch. A partial cDNA clone encoding the mouse Notch homolog, which we have termed Motch, was used to analyze expression of the Motch gene. Motch transcripts were detected in a wide variety of adult tissues, which included derivatives of all three germ layers. Differentiation of P19 embryonal carcinoma cells into neuronal cell types resulted in increased expression of Motch RNA. In the postimplantation mouse embryo Motch transcripts were first detected in mesoderm at 7.5 days post coitum (dpc). By 8.5 dpc, transcript levels were highest in presomitic mesoderm, mesenchyme and endothelial cells, while much lower levels were detected in neuroepithelium. In contrast, at 9.5 dpc, neuroepithelium was a major site of Motch expression. Transcripts were also abundant in cell types derived from neural crest. These data suggest that the Motch gene plays multiple roles in patterning and differentiation of the early postimplantation mouse embryo.

Amino Acid Sequence↗

Notching of the femoral neck during resurfacing arthroplasty of the hip: a vascular study.

During hip resurfacing arthroplasty, excessive valgus positioning or surgical technique can result in notching of the femoral neck. Although mechanical weakening and subsequent fracture of the femoral neck are well described, the potential damage to the retinacular vessels leading to an ischaemic event is relatively unknown. Using laser Doppler flowmetry, we measured the blood flow in 14 osteoarthritic femoral heads during routine total hip replacement surgery, before and after notching of the femoral neck. In ten hips there was a reduction in blood flow of more than 50% from the baseline value after simulated notching of the femoral neck. Our results suggest that femoral head vascularity in the osteoarthritic state is similar to the non-arthritic state, where damage to the extraosseous vessels can predispose to avascular necrosis. Surgeons who perform resurfacing arthroplasty of the hip should pay careful attention to these vessels by avoiding excessive dissection around the femoral neck and/or notching.

Aged↗

Frequency-specific auditory brainstem responses to clicks masked by notched noise.

Frequency-specific auditory brainstem responses were recorded as a function of the intensity of a click masked by notch-filtered white noise (i.e. band-stop-filtered). The bandwidth of the notch was fixed at five-thirds octave and the center frequency was 0.5, 1.0, 2.0 or 4.0 kHz. For normally hearing subjects the latency of the main peak in the responses is increasing with decreasing center frequency of the notch and with decreasing click intensity. At a click sensation level of 60 dB, the mean of 7 subjects' peak latency was 6.7 ms for the center frequency 4.0 kHz and 10.2 ms for the center frequency 0.5 kHz. The thresholds derived from the frequency-specific responses were within 20 dB above the subjective thresholds of audibility of the clicks as heard when masked by notched noise.

Adult↗

Derived acoustically evoked brainstem responses by means of narrow-band and notched-noise masking in normal-hearing subjects.

Derived acoustically evoked brainstem responses determined by narrow-band and notched-noise masking at 2000 Hz frequencies and below were investigated and compared with those obtained in the use of the common high-pass masking technique. With all three masking methods a dominant late wave Wa could be detected at less than or equal to 1 600 Hz centre frequencies of the derived band and this wave is typical of the excitation of the apical section of the cochlea. The latency of this wave increases when the centre frequency is decreased at a constant stimulation level. For a constant centre frequency of the derived band the latency of wave Wa increases when the stimulation level of the click and in parallel to that the masking level is decreased. Wave Wa could be found near the hearing threshold in all three masking methods. The notched-noise masking method offers major advantages provided that full masking of the frequency regions above and below the notch frequency range is carried out. A direct frequency-specific stimulation takes place and there is no need for subtracting one response from a second one. This reduces the investigation time and the memory capacity of the measuring device. The advantages and applicability of the notched-noise masking method have to be re-checked in patients with different frequency-dependent loss of hearing.

Adolescent↗

Simplified measurement of auditory filter shapes using the notched-noise method.

The shape of the auditory filter at a given centre frequency can be estimated by measuring the threshold for detecting a sinusoid presented in a spectral notch in a noise masker, as a function of notch width. Laboratory studies using this method have typically been based on threshold measurements for between 13 and 19 notch widths. In this note, we describe how both the overall sharpness and asymmetry of the auditory filter in hearing-impaired subjects can be estimated with reasonable accuracy using only five notch widths. This considerably reduces the testing time needed, making it possible to apply the method in clinical testing.

Acoustic Stimulation↗

Compression of the suprascapular nerve after fracture of the scapular notch.

A 32-year-old man with a fracture of the scapular notch associated with a lesion of the suprascapular nerve is reported. A nerve decompression operation was performed 20 months after the injury with relief of pain. The possibility that residual disability following a fracture of the scapula can be due to a lesion of the suprascapular nerve is underlined. The value of X-ray examination with projections visualizing the notch and diagnostic local anaesthetic block of the nerve passing through the notch are emphasized. Primary wide resection of the scapular notch is a preferable procedure preventing recurrence of nerve compression symptoms.

Adult↗

Cutting edge: an essential role for Notch-1 in the development of both thymus-independent and -dependent T cells in the gut.

Whereas most T cells arise in the thymus, a distinct lineage of extrathymically derived T cells is present in the gut mucosa. The developmental origin of extrathymic T cells is poorly understood. We show here that Notch-1, a transmembrane receptor involved in T cell fate specification of bipotential T/B precursors in the thymus, is absolutely required for the development of extrathymic (as well as thymus-derived) mature T cells in the intestinal epithelium. In the absence of Notch-1, CD117(+) T cell precursors are relatively more abundant in the gut than the thymus, whereas immature B cells accumulate in the thymus but not the gut. Collectively, these data demonstrate that Notch-1 is essential for both thymic and extrathymic T cell fate specification and further suggest that bipotential T/B precursors that do not receive a Notch-1 signal adopt a B cell fate in the thymus but become developmentally arrested in the gut.

Animals↗

Notch signaling suppresses IgH gene expression in chicken B cells: implication in spatially restricted expression of Serrate2/Notch1 in the bursa of Fabricius.

The bursa of Fabricius is a central organ for chicken B cell development and provides an essential microenvironment for expansion of the B cell pool and for generation of a diversified B cell repertoire. We report here that genes encoding the Notch family of transmembrane proteins, key regulators of cell fate determination in development, are differentially expressed in the bursa of Fabricius: Notch1 is expressed in medullary B cells located close to the basement membrane-associated epithelium (BMAE). In contrast, a Notch ligand, Serrate2, is expressed exclusively in the BMAE, which surrounds bursal medulla. A basic helix-loop-helix-type transcription factor, Hairy1, a downstream target of Notch signaling, is expressed in the bursa coordinately with Notch1 and Serrate2 and an immature B cell line, TLT1, which expresses both Notch1 and Serrate2. Furthermore, stable expression of a constitutively active form of chicken Notch1 or Notch2 in a B cell line results in a down-regulation of surface IgM expression, which is accompanied by the reduction of IgH gene transcripts. Transient reporter assay with the human IgH gene intronic enhancer reveals that an active form of Notch1 inhibits the IgH enhancer activity in chicken B cells, suggesting that Notch-mediated signals suppress the IgH gene expression via influencing the IgH intronic enhancer. These findings raise the possibility that the local activation of Notch1 in a subset of B cells by Serrate2 expressed in BMAE may influence the cell fate decision that is involved in B cell differentiation and selection inside the bursa.

Amino Acid Sequence↗

Dynamics of notch expression during murine prostate development and tumorigenesis.

Notch signaling has been widely demonstrated to be responsible for cell fate determination during normal development and implicated in human T-cell leukemia and mouse mammary carcinomas. Here we show that Notch signaling may be involved in prostatic development and cancer cell growth. In situ hybridization and reverse transcription-PCR analyses revealed that Notch1 was expressed in prostate epithelial cells during normal development and in prostate cancer cells. Characterization of Notch1-green fluorescent protein transgenic mice, in which the expression of reporter green fluorescent protein is under the control of the Notch1 promoter, indicated that Notch1-expressing cells were associated with the basal epithelial cell population in the prostate. Examination of the transgenic adenocarcinoma of the mouse prostate showed that expression of Notch1 was elevated in malignant prostatic epithelial cells of primary and metastatic tumors. Expression of Notch ligands, however, was low or undetectable in cultured prostate cancer cells or in malignant prostatic epithelial cells in transgenic adenocarcinoma of the mouse prostate. Furthermore, overexpression of a constitutively active form of Notch1 inhibited the proliferation of various prostate cancer cells, including DU145, LNCaP, and PC3 cells. Taken together, our data indicate for the first time that Notch signaling may play a role in murine prostatic development and tumorigenesis.

Animals↗

Auditory brainstem response to tone bursts in quiet, notch noise, highpass noise, and broadband noise.

This study investigated the effects of tone bursts (1000 Hz, 2000 Hz, and 4000 Hz) in quiet, notch noise, highpass noise, and broadband noise on the identifiability, latency, and amplitude of the auditory brainstem response (wave V). Normal listeners were presented with 40 dB and 80 dB nHL tone bursts having rise-plateau-fall times of 1 msec. Wave V was observed in all subjects at 40 dB and 80 dB nHL for the quiet and noise conditions. The latency findings suggest that responses elicited by the 80 dB nHL tone bursts in quiet were, in part, mediated by regions on the basilar membrane that did not correspond to the center frequency of the tone burst. To increase frequency-specificity, high-level tone bursts (e.g., 80 dB nHL) should be mixed with notch, highpass, or broadband noise. The use of noise conditions for low intensity levels (e.g., 40 dB nHL) does not appear necessary for isolating the response because both the notch and the highpass conditions yielded latencies similar to the quiet condition. Although similar wave V amplitudes were found at all frequencies, amplitudes were smaller for the broadband noise than for the quiet, notch, and highpass conditions. Thus, the latter conditions seem preferred.

Acoustic Stimulation↗

Anterior cruciate ligament injury versus tibial spine fracture in the skeletally immature knee: a comparison of skeletal maturation and notch width index.

Both midsubstance anterior cruciate ligament (ACL) injury and tibial spine avulsion fracture occur in the skeletally immature knee. The purpose of this study was to determine whether there are differences in skeletal maturation or notch parameters between these two groups. A retrospective case-control study of 25 skeletally immature patients with tibial spine fractures compared with 25 age- and sex-matched skeletally immature patients with midsubstance ACL injuries was performed. Bone age and notch width index were determined from preoperative radiographs. There were no significant differences between the tibial spine fracture group and the ACL injury group with respect to skeletal maturation, comparing bone age to chronological age (-0.5 vs. -0.3 years; P = 0.617). The ACL injury group had narrower notch indices than the tibial spine fracture group (0.230 vs. 0.253; P = 0.020). Thus, in a comparison of age- and sex-matched skeletally immature patients, those with midsubstance ACL injuries had a significantly narrower notch index than those with tibial spine fractures. This association may account for some of the variation in injury patterns in the skeletally immature knee.

Adolescent↗

[Rib notchings in Cooley's anemia].

In 3 cases of Cooley's anemia rib notchings were found. In the first case the clinical pattern did not allow to exclude postductal type of aortic coarctation and thus was performed a venous digital aortography (SVC) showing the integrity of the aortic arch and the absence of intercostal arterial collateral circulation. Only two previous descriptions of rib notchings in thalassemia were found in literature, and the authors shortly describe the 3 observed cases and suggest some possible pathogenetic interpretations either of rib notchings in thalassemia or of the relatively late appearance (adolescence) of rib notchings.

Adolescent↗

[Relationship between the spike potentials of "local" intra-atrial and esophageal electrocardiograms of the atria and notched P wave of ECG from the body surface].

The interrelationship of spike potentials of "local" intraatrial and esophageal electrograms and notched P wave of an intensified ECG recorded from the body surface was studied. It was found that the process of excitation in the region of the sinus node is reflected in the slow deviation of the P wave of intensified ECG, preceding the appearance of the P wave of an ordinary ECG recorded from the body surface. The A1 spike of a "local" electrogram reflecting the penetration of excitation into the right atrium is manifested in the form of the first notch of the P wave on an intensified ECG. The A2 spike reflecting the arrival of the excitation to the atrioventricular node is manifested in the form of a notch--the first peak of the P wave. The A1(2)) spike reflecting the arrival of the excitation to the left atrium along Bachmann's bundle is manifested as the second peak of the P wave (A1(2)). The A3 spike of the "local" electrogram reflecting the arrival of the excitation from the left atrium to the orifice of the coronary sinus is manifested in the form of the second notch of the P wave (A3).

Action Potentials↗

The clinical implications of early diastolic notch in third trimester Doppler waveform analysis of the uterine artery.

To evaluate the clinical utility of third trimester Doppler waveform analysis of the uterine artery in predicting complicated pregnancies and fetal well-being, we compared adverse pregnancy outcomes in 2321 women with the presence of an elevated systolic-diastolic ratio (greater than 2.6) with the persistence of an early diastolic notch and with the combination of an elevated systolic-diastolic ratio and an early diastolic notch. The positive predictive values are 47.5%, 82.9%, and 92.6%, respectively. From these data we can conclude that determination of the presence or absence of an early diastolic notch is more valuable in predicting the perinatal outcome than is the presence of an elevated systolic-diastolic ratio alone. We also suggest that an assessment of the uterine artery systolic-diastolic ratio combined with the evaluation for persistent early diastolic notch would be a clinically useful test for fetal well-being.

Apgar Score↗

Electrocardiographic low-frequency QRS notching and ventilatory impairment in patients with pulmonary tuberculosis.

The occurrence of notching in the initial and terminal parts of the QRS complex of the ECG was studied in a series of 1072 patients with active or healed pulmonary tuberculosis. Terminal notchings were associated with ventilatory impairment: in the male group the percentage of patients with terminal notching increased from 5 to 20% as the FEV1.0% decreased from larger than or equal to 80 to below 40. Initial notchings were not associated with ventilatory impairment. The relationships were similar when studied separately in groups with and without left heart disease.

Electrocardiography↗

Shape optimisation of a Charnley prosthesis based on the fatigue notch factor.

The femoral component of the artificial hip joint implanted in a patient's femur is subjected to a complex set of forces exerted due to normal life activities. It is thought that high values of stress in the cement in a cemented prosthesis can lead to fractures of the cement mantle and loosening of the stem. The incidence of such problems may be diminished by reduction of the fatigue notch factor in the cement, such that stress concentrations are avoided and the crack initiation time maximised. This study describes a method for numerical shape optimisation to determine an optimal shape for the femoral stem of a hip prosthesis in order to minimise the fatigue notch factor in the cement layer at the interfaces with the bone and stem whilst at the same time maintaining or increasing the stress levels in the proximal medial femoral bone to help prevent stress shielding. The method when used to optimise the shape of a stainless steel Charnley stem was found to be extremely efficient and effective. The resulting optimal shape was heavily waisted in the proximal region below the neck but distally was quite similar to the original design. The fatigue notch factors in the cement were reduced by 16% and 19% for medial and lateral cement/stem interfaces, respectively, and by 8% and 2% for the corresponding cement/bone interfaces. The fatigue notch factor in the proximal medial bone was increased by 57% which indicates that the general stress level in this region is markedly increased. Thus the optimised design should increase the fatigue life of the cement and at the same time reduce stress shielding in the proximal bone. Both of these effects may help prevent loosening of the femoral component and hence reduce the need for early revision operations.

Aged↗

Intercondylar notch encroachment following anterior cruciate ligament reconstruction: a prospective study.

Intercondylar notch impingement is a recognized cause of graft failure following anterior cruciate ligament (ACL) reconstruction and typically is attributed to anterior tibial tunnel placement or inadequate notchplasty. This prospective study assessed the incidence and nature of notch regrowth following initial ACL reconstruction. The study population was comprised of 36 patients who underwent ACL reconstruction using a patellar tendon-bone autograft. A 3- to 5-mm notchplasty was performed in all patients, and an intraoperative radiograph was taken confirming proper tunnel placement. Magnetic resonance imaging (MRI) was performed the first week following surgery and again at 6 months. The MRIs were reviewed by two skeletal radiologists to evaluate postoperative notch and graft changes. Of the 36 study patients, 28 (78%) knees showed no evidence of graft impingement as defined by graft indentation and intra-substance edema. The MRIs of 8 (22%) patients showed evidence of graft impingement. Four patients had clinical signs of graft impingement, namely persistent effusion or lack of full extension. Arthroscopically, 3 of these patients demonstrated graft encroachment and impingement by fibrocartilage with areas of immature bone. These results indicate that graft impingement from regrowth of the notch is a clinically relevant phenomenon that could potentially result in late graft demise in the ACL-reconstructed knee.

Adult↗

Cetobacterium somerae ZNN-1 promotes goblet cell differentiation through glutamine-mediated Notch signaling suppression.

INTRODUCTION: The gut microbiota acts as a crucial mediator in the interaction between the diet components and the host metabolism. However, the molecular mechanism by which the gut microbiota adapts to dietary components and subsequently regulates host physiological responses remains unclear. OBJECTIVES: This study aimed to investigate the response of gut microbiota to a plant-based protein diet (soybean meal, SM) and the effects of gut microbiota on host intestinal barrier function, along with the underlying mechanisms in a fish model. METHODS: Histopathological examination, and transepithelial electrical resistance test were used to evaluate the effects of Cetobacterium somerae on intestinal barrier function. Potential molecular mechanisms were validated by integrating whole-genome sequencing, microbiota composition sequencing, transcriptomics, and metabolomics, and utilizing in vitro cell models and mouse-derived organoid models. RESULTS: The results revealed that the SM diet significantly increased the abundance of Cetobacterium somerae in fish. Administration of C.somerae ZNN-1, a dominant strain isolated from the intestine of fish fed with the SM diet, enhanced the intestinal barrier function, particularly increasing the number of goblet cells in the intestine. Whole genome analysis of C. somerae ZNN-1 showed carbohydrate metabolism-associated genes were the most abundant in its metabolic modules. C.somerae ZNN-1 supplementation significantly inhibited the Notch signaling pathway in fish intestine. Metabolomics analysis revealed that administration of C.somerae ZNN-1 increased the glutamine level in fish gut. In vitro experiments demonstrated that glutamine regulated the differentiation of goblet cell by inhibiting the Notch signaling pathway in both human intestinal epithelial cell model and mouse intestinal organoid model. CONCLUSION: C. somerae served as a key bacterium adapted to soybean meal-derived carbohydrates, and it promoted goblet cell differentiation by inhibiting the Notch pathway. This study provides a new perspective for unraveling the interaction mechanisms among diet components, intestinal microbiota and host health.

Animals↗