Notch

The rapid turnover of intestinal epithelial cells is maintained by a small number of stem cells located in pocket-like gland structures called crypts. While our understanding of the identity and function of intestinal stem cells (ISCs) has rapidly progressed, epigenetic and transcriptional regulation in crypt stem cell and progenitor pools remains an active field of investigation. Surrounded by various types of cells in the stroma, crypt progenitors display high levels of plasticity, harboring the ability to interconvert in the face of epithelial damage...

Neuritin plays a key role in neural development and regeneration by promoting neurite outgrowth and synapse maturation. However, the mechanism of neuritin in modulating neurite growth has not been elucidated. Here, using yeast two-hybrid we screened and discovered the interaction of neuritin and neuralized (NEURL1), which is an important regulator that can activate Notch signaling through promoting endocytosis of Notch ligand. And then we identified the interaction of neuritin and neuralized by co-immunoprecipitation (IP) assays, and clarified that neuritin and NEURL1 were co-localized on the cell membrane of SH-SY5Y cells...

Taste cells undergo constant turnover throughout life; however, the molecular mechanisms governing taste cell generation are not well understood. Using RNA-Seq, we systematically surveyed the transcriptome landscape of taste organoids at different stages of growth. Our data show the staged expression of a variety of genes and identify multiple signaling pathways underlying taste cell differentiation and taste stem/progenitor cell proliferation. For example, transcripts of taste receptors appear only or predominantly in late-stage organoids...

To clarify the cause of posterolateral rotatory instability after damage to the lateral ulnar collateral ligament (LUCL), the morphological characteristics of the LUCL were reinvestigated and three-dimensional (3D) image of the ligament was reconstructed using 35 human elbows. The results were as follows: 1) the insertion point of the LUCL on the humerus was almost at the center of the capitellum, and its width was 2.61 ± 1.02 mm. The insertion point of the LUCL on the ulna was located from the lesser sigmoid notch to the supinator crest and had a width of 9...

The remarkable capacity of the adult olfactory epithelium (OE) to regenerate fully both neurosensory and nonneuronal cell types after severe epithelial injury depends on life-long persistence of two stem cell populations: the horizontal basal cells (HBCs), which are quiescent and held in reserve, and mitotically active globose basal cells. It has recently been demonstrated that down-regulation of the ΔN form of the transcription factor p63 is both necessary and sufficient to release HBCs from dormancy. However, the mechanisms by which p63 is down-regulated after acute OE injury remain unknown...

BACKGROUND: In mammalian intestines, Notch signaling plays a critical role in mediating cell fate decisions; it promotes the absorptive (or enterocyte) cell fate, while concomitantly inhibiting the secretory cell fate (i.e. goblet, Paneth and enteroendocrine cells). We recently reported that intestinal-specific Kaiso overexpressing mice (Kaiso (Tg) ) exhibited chronic intestinal inflammation and had increased numbers of all three secretory cell types, hinting that Kaiso might regulate Notch signaling in the gut...

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Many studies are based on the hypothesis that recurrence and drug resistance in lung carcinoma are due to a subpopulation of cancer stem-like cells (CSLCs) in solid tumors. Therefore it is crucial to screen for and recognize lung CSLCs. In this study, we stimulated non-small cell lung cancer (NSCLC) A549 cells to display stem cell-like characteristics using a combination of five small molecule compounds. The putative A549 stem cells activated an important CSLC marker, CD133 protein, as well multiple CSLC-related genes including ATP-binding cassette transporter G2 (ABCG2), C-X-C chemokine receptor type 4 (CXCR4), NESTIN, and BMI1...

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality. Recent studies have stated that NOTCH signaling plays an important role in the development and progression of CRC. However, the role of Jagged-2 (JAG2), one of the NOTCH ligands, has not been delineated in colorectal tumorigenesis and drug resistance. In the present study, we have examined the impact of targeting JAG2 on CRC cells. Among all the members of NOTCH ligands, only the expression of JAG2 was found up-regulated in the intestinal tumors of ApcMin/+ mice as compared to the nearby normal mucosa...

In the epipelagic ocean the genus Oithona is considered as one of the most abundant and widespread copepods and plays an important role in the trophic food web. Despite its ecological importance, little is known about the Oithona and cyclopoid copepods genomics. Therefore, we sequenced, assembled and annotated the genome of Oithona nana. The comparative genomic analysis integrating available copepod genomes highlighted the expansions of genes related to stress response, cell differentiation, and development, including genes coding Lin12-Notch-Repeat (LNR) domain proteins...

Phylogenetic analysis of early tetrapod evolution has resulted in a consensus across diverse data sets in which the tetrapod stem group is a relatively homogenous collection of medium- to large-sized animals showing a progressive loss of 'fish' characters as they become increasingly terrestrial, whereas the crown group demonstrates marked morphological diversity and disparity. The oldest fossil attributed to the tetrapod crown group is the highly specialized aïstopod Lethiscus stocki, which shows a small size, extreme axial elongation, loss of limbs, spool-shaped vertebral centra, and a skull with reduced centres of ossification, in common with an otherwise disparate group of small animals known as lepospondyls...

The role of the Notch ligand Jagged1 in hepatic fibrosis remains to be elucidated. In the current study, we investigated the role of Jagged1 in the activation of hepatic stellate cells (HSCs) and development of hepatic fibrosis in rats. In vitro, Jagged1 in HSCs was downregulated and upregulated by Jagged1 siRNA and pcDNA3.1 Jagged1, respectively. The levels of epithelial-mesenchymal transition (EMT) markers and HSC activation markers were assessed using western blot analysis. The proliferation and migration capacity of HSCs were assessed using 5-ethynyl-2'-deoxyuridine (EdU) incorporation and Transwell migration assays...

NOTCH is a fundamental signaling system that regulates normal embryonic development and tissue homeostasis in adult life. NOTCH receptor is a single-pass transmembrane protein normally triggered via direct cell-to-cell contact, in which NOTCH ligands bind the extracellular domain of the receptor, inducing γ-secretase cleavage and release of intracellular domain. The intracellular domain binds to the transcriptional effector RBPJκ to activate transcription of target genes that regulate cell differentiation, patterning, and morphogenesis during embryonic development and adult life...

OBJECTIVE: Bilateral audiometric notch (BN) at 4000-6000 Hz was identified as a noise-induced hearing loss (NIHL) phenotype for genetic association analysis in college-aged musicians. This study analysed BN in a sample of US youth. DESIGN: Prevalence of the BN within the study sample was determined and logistic-regression analyses were performed to identify audiologic and other demographic factors associated with BN. Computer-simulated "flat" audiograms were used to estimate potential influence of false-positive rates in estimating the prevalence of the BN...

VAMP/synaptobrevin-associated proteins (VAPs) contain an N-terminal major sperm protein domain (MSPd) that is associated with amyotrophic lateral sclerosis. VAPs have an intracellular housekeeping function, as well as an extracellular signaling function mediated by the secreted MSPd. Here we show that the C. elegans VAP homolog VPR-1 is essential for gonad development. vpr-1 null mutants are maternal effect sterile due to arrested gonadogenesis following embryo hatching. Somatic gonadal precursor cells and germ cells fail to proliferate fully and complete their respective differentiation programs...

Cells differentiate into specific and functional lineages to build up tissues. It has been shown in several tissues that mitochondrial morphology, levels of "mitochondrial shaping" proteins, and mitochondrial functions change upon differentiation. In this review, we highlight the significance of mitochondrial dynamics and functions in tissue development, cell differentiation, and reprogramming processes. Signalling cascades are critical for tissue stem cell maintenance and cell fate determination, and growing evidence demonstrates mitochondria could act as a centre of intra and extracellular signals to coordinate signalling pathways, such as Notch, Wnt, and YAP/TAZ signalling...

BACKGROUND: The available comparative studies of computer navigation-assisted and conventional knee arthroplasties have short-term follow-up periods. Therefore, the clinical benefits after long-term follow-up are not clear. The purposes of the current long-term study were to compare clinical outcomes, alignment of the knee components, prevalence of aseptic loosening of the components, implant survival, and complications of total knee arthroplasties performed with and without computer navigation...

The aim of this study was to investigate the effects of Norgestrel (NGT) on the gonadal development in adult zebrafish. Adult zebrafish were exposed to NGT for 14 days at 871 ng L(-1) for microarray analysis, and a follow-up experiment was conducted to further study targeted pathway in adult zebrafish after exposure to NGT at 6.7 ng L(-1) , 83 ng L(-1) and 912 ng L(-1) by quantitative PCR (qPCR) and histology analysis. The microarray analysis revealed that 11545 transcripts were identified. Gene ontology analysis showed organ development, system development, multicellular organismal development, single-organism developmental process and developmental process were significantly enriched...

With the introduction of next-generation sequencing, the genetic landscape of the complex group of B-cell lymphoid malignancies has rapidly been unravelled in recent years. This has provided important information about recurrent genetic events and identified key pathways deregulated in each lymphoma subtype. In parallel, there has been intense search and development of novel types of targeted therapy that 'hit' central mechanisms in lymphoma pathobiology, such as BTK, PI3K or BCL2 inhibitors. In this review, we will outline the current view of the genetic landscape of selected entities: follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, chronic lymphocytic leukaemia and marginal zone lymphoma...

The purpose of this article is to determine normative values for the length of the acetabular rim and detect differences between gender, age, ethnicity, height and leg length. Six measurements were taken on the acetabular rim of 143 cadaveric skeleton specimens (286 acetabula) using a coordinate-measuring device: circumferential (excluding acetabular notch), anterior inferior iliac spine (AIIS)-anterior, AIIS-posterior, 12-3 o'clock, 12-9 o'clock and 11-5 o'clock. Museum specimen height data and leg length data from a previous study were recorded for 109 of 143 specimens...