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Biomedical subjects

J Jang

Publications and source records attributed to J Jang.

At least 19 recordsLinked to original sources

Notch1 confers thymocytes a resistance to GC-induced apoptosis through Deltex1 by blocking the recruitment of p300 to the SRG3 promoter.

One notable phenotypic change during the differentiation of immature thymocytes into either mature CD4 or CD8 single-positive lineages is the acquisition of a resistance to glucocorticoid (GC)-induced apoptosis. We have previously reported that SRG3 is critical in determining the sensitivity for the GC-induced apoptosis in developing thymocytes. We report here that Notch signaling downregulates the transcriptional activation of SRG3 through N-box and/or E-box elements on its promoter. RBP-J represses SRG3 transcription through the N-box motif. On the other hand, Deltex1 competitively inhibits the binding of p300 to E2A/HEB protein bound to the E-box elements and represses the SRG3 promoter activity. Moreover, enforced expression of Deltex1 restored double-positive (DP) thymocyte survival from the GC-induced apoptosis. Our results suggest that Notch signaling confers differentiating DP thymocytes resistance to GCs by regulating the SRG3 expression through Deltex1, and that Deltex1 and SRG3 may play a significant role during DP thymocyte maturation.

Animals↗

Characterization of crystallographic properties of SMC poly Si using electron backscattered diffraction.

Crystallographic properties of silicide mediated crystallization (SMC) polycrystalline silicon (poly Si) and excimer laser annealing (ELA) poly Si were studied by electron backscattered diffraction. Large-grain sized poly Si with a large fraction of low-angle grain boundaries was acquired by SMC, and small-grain sized poly Si with high-angle grain boundaries especially around 60 degrees was acquired by ELA. The thin film transistor (TFT) device characteristics were investigated in view of short-range crystallinity (pattern quality) and long-range crystallinity (misorientation distribution) of the specimens. Short-range crystallinity did not significantly affect the TFT device characteristics, and long-range crystallinity considering the low energy level of special boundaries could be better related to the TFT device characteristics of poly Si.

Journal Article↗

Anomalous surface diffusion in nanoscale direct deposition processes.

We report the first observation of anomalous diffusion in nanometer scale direct deposition processes utilizing dip-pen nanolithography (DPN). DPN permits quite general nanostructure patterns to be drawn on flat surfaces. Here we demonstrate experimentally, and discuss theoretically, the situation in which the molecular ink in DPN binds weakly to the surface. We observe, for the weak-binding case of 1-dodecylamine on mica, that anomalous diffusion occurs, leading to nearly fractal deposition patterns.

Journal Article↗

Promoter analysis of the Drosophila melanogaster gene encoding the pterin 4alpha-carbinolamine dehydratase.

Pterin-4alpha-carbinolamine dehydratase (PCD) is a key enzyme in the regeneration pathway of tetrahydrobiopterin. Previously, we isolated and reported the Drosophila melanogaster gene encoding PCD. In the present study, we isolated and characterized the Drosophila virilis gene encoding PCD. The Drosophila virilis PCD gene has two introns and an open reading frame to encode a protein of 101 amino acids. The amino acid sequence of Drosophila virilis PCD shows a 83% homology to that of the Drosophila melanogaster PCD protein. From the alignment of the nucleotide sequence in the 5'-flanking region of the Drosophila melanogaster and Drosophila virilis PCD genes, we found four conserved sequences. Using a transient transfection assay, we showed that one of the conserved sequences (-127 to approximately -115) is critical for expression, also the minimal promoter region between -127 and +51 is necessary for the efficient expression of Drosophila melanogaster PCD.

Amino Acid Sequence↗

Notch1 confers a resistance to glucocorticoid-induced apoptosis on developing thymocytes by down-regulating SRG3 expression.

We previously have reported that SRG3 is required for glucocorticoid (GC)-induced apoptosis in the S49.1 thymoma cell line. Activation of Notch1 was shown to induce GC resistance in thymocytes. However, the specific downstream target of Notch1 that confers GC resistance on thymocytes is currently unknown. We found that the expression level of SRG3 was critical in determining GC sensitivity in developing thymocytes. The expression of SRG3 also was down-regulated by the activated form of Notch1 (NotchIC). The promoter activity of the SRG3 gene also was down-regulated by NotchIC. Expression of transgenic SRG3 resulted in the restoration of GC sensitivity in thymocytes expressing transgenic Notch1. These results suggest that SRG3 is the downstream target of Notch1 in regulating GC sensitivity of thymocytes.

Animals↗

Protein kinase Cdc15 activates the Dbf2-Mob1 kinase complex.

Exit from mitosis in budding yeast requires inactivation of cyclin-dependent kinases through mechanisms triggered by the protein phosphatase Cdc14. Cdc14 activity, in turn, is regulated by a group of proteins, the mitotic exit network (MEN), which includes Lte1, Tem1, Cdc5, Cdc15, Dbf2/Dbf20, and Mob1. The direct biochemical interactions between the components of the MEN remain largely unresolved. Here, we investigate the mechanisms that underlie activation of the protein kinase Dbf2. Dbf2 kinase activity depended on Tem1, Cdc15, and Mob1 in vivo. In vitro, recombinant protein kinase Cdc15 activated recombinant Dbf2, but only when Dbf2 was bound to Mob1. Conserved phosphorylation sites Ser-374 and Thr-544 (present in the human, Caenorhabditis elegans, and Drosophila melanogaster relatives of Dbf2) were required for DBF2 function in vivo, and activation of Dbf2-Mob1 by Cdc15 in vitro. Although Cdc15 phosphorylated Dbf2, Dbf2-Mob1, and Dbf2(S374A/T544A)-Mob1, the pattern of phosphate incorporation into Dbf2 was substantially altered by either the S374A T544A mutations or omission of Mob1. Thus, Cdc15 promotes the exit from mitosis by directly switching on the kinase activity of Dbf2. We propose that Mob1 promotes this activation process by enabling Cdc15 to phosphorylate the critical Ser-374 and Thr-544 phosphoacceptor sites of Dbf2.

Cell Cycle↗

Haloperidol and clozapine increase neural activity in the rat prefrontal cortex.

Haloperidol and clozapine have been widely used to alleviate schizophrenic symptoms, but their physiological effects in the prefrontal cortex (PFC) are not known. Effects of haloperidol and clozapine on single unit activity were investigated in the medial PFC of anesthetized rats. Injection (intraperitoneal) of haloperidol (1 mg/kg) or clozapine (20 mg/kg) significantly elevated discharge rates of PFC neurons. Considering that hypofrontality is one characteristic of schizophrenic symptoms, these results raise the possibility that enhancement of PFC neural activity contributes to therapeutic effects of haloperidol and clozapine.

Action Potentials↗

Comparative studies of various run buffers for chiral capillary electrophoresis using chiral crown ether as a chiral selector.

In the capillary electrophoretic separation of primary amine enantiomers using (+)-(18-crown-6)-tetracarboxylic acid (18C6H4) as a chiral selector, the presence of run buffer constituents such as tris(hydroxymethyl)aminomethane (Tris) or Na+ competing with analytes for 18C6H4, diminishes the effectiveness of 18C6H4. In order to determine appropriate buffer systems for 18C6H4, various run buffer cationic components including Tris, 1,3-bis[tris(hydroxymethyl)methylamino]propane, bis(2-hydroxyethyl)iminotris(hydroxymethyl)methane, triethanolamine, tetramethylammonium, and Na+ were compared. Quantitative studies of the effects of the competitive constituents were carried out by measuring the electrophoretic mobilities of histidine as a function of the 18C6H4 concentration. We also derived a simple equation to estimate the optimal chiral selector concentration for a maximum mobility difference in the presence of a competitive inhibitor.

Amines↗

Synthesis of (+/-)-methyl-(1-aryl-4-pyridin-3-yl-but-3-enyl)-amines.

trans-Metanicotine, a subtype (alpha4beta2)-selective ligand for neuronal nicotinic acetylcholine receptor, is under clinical phase for Alzheimer's disease. An efficient synthetic route for (+/-)-methyl-(1-aryl-4-pyridin-3-yl-but-3-enyl)-amines, derivatives of trans-metanicotine, was explored. Allylation reaction of aryl aldimines with allylmagnesium bromide in THF gave (+/-)-methyl-(1-aryl-but-3-enyl)-amines. Protection of the amines with the Boc group and following Heck reaction of the N-Boc amines with 3-bromopyridine gave (+/-)-methyl-(1-aryl-4-pyridin-3-yl-but-3-enyl)-carbamic acid tert-butyl esters. Deprotection of the N-Boc group in aqueous 1N-HCI solution gave the titled amines in good yields. Thus, trans-metanicotine analogues modified at the a-position of the methylamino group with aryl groups were obtained in 5 steps.

Nicotine↗

Fast spiking and regular spiking neural correlates of fear conditioning in the medial prefrontal cortex of the rat.

In order to investigate whether and how medial prefrontal cortex (mPFC) of the rat is involved in processing of information related to fear conditioning, we recorded from single units in the prelimbic and infralimbic cortex of fear-conditioned rats in response to an explicit conditional stimulus (CS; an auditory tone) or contextual cues (conditioning box). The majority of units changed their activities significantly in response to the CS in a delay or trace conditioning paradigm. Both transient and tonic activity changes, including delay cell activity, were observed as in other behavioral tasks. When exposed to the context without CS delivery, most units changed their activities as well. These results show that both tone and contextual information are processed in the rat mPFC in expectation of the delivery of an aversive stimulus (electric foot shock). Interestingly, fast spiking cells (putative inhibitory interneurons) and regular spiking cells (putative projection neurons) showed different patterns of responses. Fast spiking cells tended to show transient responses and increased their firing rates following CS presentation, whereas a complementary pattern was observed in the regular spiking cells. Our results enhance our understanding of the neural mechanisms underlying prediction of an aversive stimulus in the mPFC.

Acoustic Stimulation↗

Acinic cell carcinoma of the lacrimal gland with intracranial extension: a case report.

PURPOSE: To describe a patient with acinic cell carcinoma of the lacrimal gland presenting with atypical manifestations including erosion of the orbital roof and intracranial extension. We compare his clinical manifestations with two previously reported cases. METHODS: Case report. RESULTS: A 51-year-old man presented with a firm, tender, palpable mass in the superior temporal portion of his right orbit. CT scan demonstrated a large homogeneously enhancing mass displacing the globe inferiorly and eroding the roof of the orbit. MRI of the orbit showed intracranial extension of tumor. Biopsy revealed an acinic cell carcinoma of the lacrimal gland. CONCLUSIONS: Acinic cell carcinoma is a rare neoplasm occurring primarily in the major and minor salivary glands.

Carcinoma, Acinar Cell↗

A concise synthetic pathway for trans-metanicotine analogues.

A convenient pathway for synthesis of trans-metanicotine analogues was developed. trans-Metanicotine, a subtype (alpha4beta2)-selective ligand for neuronal nicotinic acetylcholine receptor, is under clinical phase for Alzheimer's disease. Zn-mediated allylation of allyl bromide and acetaldehyde followed by Heck reaction with 3-bromopyridine gave 5-pyridin-3-yl-pent-4-en-3-ol (2). Tosylation of 5-pyridin-3-yl-pent-4-en-3-ol followed by substitution reaction with methylamine in sealed tube gave methyl-(1-methyl-4-pyridin-3-yl-but-3-enyl)-amine (4) in good yields. Thus, trans-metanicotine analogues modified at the alpha-position of the methylamino group with various functional groups can be obtained in 4 steps.

Nicotine↗

"Malgun" (clear) cell change of gastric epithelium in chronic Helicobacter pylori gastritis.

To characterize the Helicobacter pylori gastritis-associated epithelial change, we analyzed 251 randomly selected gastric biopsies. The "malgun" (clear) cell change of the gastric epithelium was noted in 229 biopsies (91.2%). Malgun cells were characterized by large, pale nuclei with a euchromatin pattern, enlarged nucleoli, and clear cytoplasm. In the proliferative zone, individual malgun cells and small clusters were often in close contact with infiltrating neutrophils, suggesting that they had developed individually in the background of acute foveolitis. Mitotic figures of malgun cells were not infrequent, including atypical ones. In the surface epithelium, most malgun cells were in clusters that were often large enough to occupy wide epithelial segments. With Warthin-Starry triple staining, they were distinguished by the absence of silver impregnation, while other cells showed staining of the heterochromatin. They displayed prominent immunostaining for low molecular weight cytokeratin (No. 8). Most malgun cells were PCNA-positive in both surface and proliferative zones, whereas Ki67-positive cells were found only in the proliferative zone. It was suggested that a population of malgun cells, which were positive for PCNA only, were in the process of active DNA repair. The malgun cell change may represent a "cellular pattern of activation" in a population which had significant DNA damage, but somehow escaped the detection by the apoptosis system. The notion of "damage at the genetic level" was supported by the observation that these cells remained at least for 8 weeks after eradication of the H. pylori infection.

Adult↗

Preparation and solubility in acid and water of partially deacetylated chitins.

Partially deacetylated chitins with different degrees of deacetylation (DD) were prepared by alkaline treatment under homogeneous conditions, and the effect of DD on their solubility was discussed in terms of crystal structure and mode of hydrogen bonding. With an increase in the treatment time, the DD of chitin increased proportionally. The chitin became soluble in dilute acetic acid at the DD of ca. 28% or over and soluble in water at the DD of ca. 49%. The solubility of the partially deacetylated chitins had a close relationship with their crystal structure, crystallinity, and crystal imperfection as well as the glucosamine content. The wide-angle X-ray diffractometry (WAXD) revealed that the chitin with ca. 28% DD retained the crystal structure of alpha-chitin with significantly reduced crystallinity and perfection of the crystallites. The water-soluble chitin of ca. 49% DD had a new crystal structure similar to that of beta-chitin rather than either alpha-chitin or chitosan, suggesting that the homogeneous deacetylation transformed the crystal structure of chitin from the alpha to the beta form. Some hydrogen bonds existing in raw alpha-chitin were found to be missing at a DD of ca. 49%.

Acetylation↗

Somatic mutations of Fas (Apo-1/CD95) gene in cutaneous squamous cell carcinoma arising from a burn scar.

Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signaling, and recent reports have suggested that defects within the Fas receptor pathway such as Fas mutation play an important part in the development and progression of human tumors. Burn scar-related squamous cell carcinoma of skin is a unique subtype of cutaneous squamous cell carcinoma, and tends to be more aggressive in nature than conventional squamous cell carcinoma. The molecular mechanisms underlying the development and progression of burn scar-related squamous cell carcinoma, however, are not clear. In this study, we analyzed the entire coding region and all splice sites of the Fas gene for the detection of the somatic mutations in a series of 50 conventional squamous cell carcinomas and 21 burn scar-related squamous cell carcinomas by polymerase chain reaction, single strand conformation polymorphism, and DNA sequencing. We detected mis-sense mutations in three of 21 burn scar-related squamous cell carcinomas (14.3%), whereas no mutation was detected in 50 conventional squamous cell carcinomas. Of the three Fas mutations detected in the burn scar-related squamous cell carcinomas, one was found in Fas ligand-binding domain, another one was identified in the death domain known to be involved in the transduction of an apoptotic signal, and the other one was found in the transmembrane domain. Our data show that some burn scar-related squamous cell carcinomas have Fas gene mutations in important regions for the apoptosis function and suggest that these mutations might be involved in the pathogenesis of burn scar-related squamous cell carcinomas. In addition, our results provide an important clue to understanding the difference between burn scar-related squamous cell carcinoma and conventional squamous cell carcinoma at the molecular level.

Adolescent↗

Exit from mitosis is triggered by Tem1-dependent release of the protein phosphatase Cdc14 from nucleolar RENT complex.

Exit from mitosis in budding yeast requires a group of essential proteins--including the GTPase Tem1 and the protein phosphatase Cdc14--that downregulate cyclin-dependent kinase activity. We identified a mutation, net1-1, that bypasses the lethality of tem1 delta. NET1 encodes a novel protein, and mass spectrometric analysis reveals that it is a key component of a multifunctional complex, denoted RENT (for regulator of nucleolar silencing and telophase), that also contains Cdc14 and the silencing regulator Sir2. From G1 through anaphase, RENT localizes to the nucleolus, and Cdc14 activity is inhibited by Net1. In late anaphase, Cdc14 dissociates from RENT, disperses throughout the cell in a Tem1-dependent manner, and ultimately triggers mitotic exit. Nucleolar sequestration may be a general mechanism for the regulation of diverse biological processes.

Cell Cycle Proteins↗