Spindle and Giant Cell Type Undifferentiated Carcinoma of the Proximal Bile Duct

Undifferentiated spindle and giant cell carcinoma is an extremely rare malignant neoplasm arising in the extrahepatic bile duct. We herein present the case of a 67-year-old male who developed an undifferentiated spindle and giant cell carcinoma of the proximal bile duct. A nodular infiltrating tumor was located at the proximal bile duct, resulting in obstructive jaundice. Histologically, the tumor was composed of mainly spindle-shaped and giant cells and showed positive immunoreactivity for both cytokeratin and vimentin. Adjuvant chemotherapy was administered following extrahepatic bile duct resection, and he has been doing well for 16 months since the surgical treatment. The literature on this rare malignancy is also reviewed and discussed

Totally disconnected sets, Jordan curves, and conformal maps

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43186/1/10998_2005_Article_BF02018646.pd

SUMOylation of DEC1 Protein Regulates Its Transcriptional Activity and Enhances Its Stability

Differentiated embryo-chondrocyte expressed gene 1 (DEC1, also known as sharp2, stra13, or BHLHB2) is a mammalian basic helix-loop-helix protein that is involved in many aspects of gene regulation through acting as a transcription factor. Changes in DEC1 expression levels have been implicated in the development of cancers. Using COS-7 cell, we showed that DEC1 can be modified by the small ubiquitin-like modifiers, SUMO1, 2 and 3. Two major SUMOylation sites (K159 and K279) were identified in the C-terminal domain of DEC1. Substitution of either K159 or K279 with arginine reduced DEC1 SUMOylation, but substitution of both K159 and K279 abolished SUMOylation, and more protein appeared to be retained in the cytoplasm compared to wild-type DEC1. The expression of DEC1 was up-regulated after serum starvation as previously reported, but at the same time, serum starvation also led to more SUMOylation of DEC1. In MCF-7 cells SUMOylation also stabilized DEC1 through inhibiting its ubiquitination. Moreover, SUMOylation of DEC1 promoted its repression of CLOCK/BMAL1-mediated transcriptional activity through recruitment of histone deacetylase1. These findings suggested that posttranslational modification of DEC1 in the form of SUMOylation may serve as a key factor that regulates the function of DEC1 in vivo

Derivation of Human Differential Photoreceptor-like Cells from the Iris by Defined Combinations of CRX, RX and NEUROD

Examples of direct differentiation by defined transcription factors have been provided for beta-cells, cardiomyocytes and neurons. In the human visual system, there are four kinds of photoreceptors in the retina. Neural retina and iris-pigmented epithelium (IPE) share a common developmental origin, leading us to test whether human iris cells could differentiate to retinal neurons. We here define the transcription factor combinations that can determine human photoreceptor cell fate. Expression of rhodopsin, blue opsin and green/red opsin in induced photoreceptor cells were dependent on combinations of transcription factors: A combination of CRX and NEUROD induced rhodopsin and blue opsin, but did not induce green opsin; a combination of CRX and RX induced blue opsin and green/red opsin, but did not induce rhodopsin. Phototransduction-related genes as well as opsin genes were up-regulated in those cells. Functional analysis; i.e. patch clamp recordings, clearly revealed that generated photoreceptor cells, induced by CRX, RX and NEUROD, responded to light. The response was an inward current instead of the typical outward current. These data suggest that photosensitive photoreceptor cells can be generated by combinations of transcription factors. The combination of CRX and RX generate immature photoreceptors: and additional NEUROD promotes maturation. These findings contribute substantially to a major advance toward eventual cell-based therapy for retinal degenerative diseases

Status and future prospect of 48Ca double beta decay search in CANDLES

The observation of neutrino-less double beta decay (0νββ) would be the most practical way to prove the Majorana nature of the neutrino and lepton number violation. CANDLES studies 48Ca double beta decay using CaF2 scintillator. The main advantage of 48Ca is that it has the highest Q-value (4.27 MeV) among all the isotope candidates for 0νββ. The CANDLES III detector is currently operating with 300kg CaF2 crystals in the Kamioka underground observatory, Japan. In 2014, a detector cooling system and a magnetic cancellation coil was installed with the aim to increase light emission of CaF2 scintillator and photo-electron collection efficiency of the photo-multipliers. After this upgrade, light yield was increased to 1000 p.e./MeV which is 1.6 times larger than before. According to data analysis and simulation, main background source in CANDLES is turned out to be high energy external gamma-ray originating neutron capture on the surrounding materials, so called (n,γ). Upgrading the detector by installing neutron and gamma-ray shield can reduce the remaining main backgrounds by two order magnitude. In this report, we discuss the detail of (n,γ) and background reduction by additional shielding

Status and future prospect of 48Ca double beta decay search in CANDLES

The observation of neutrino-less double beta decay (0νββ) would be the most practical way to prove the Majorana nature of the neutrino and lepton number violation. CANDLES studies 48Ca double beta decay using CaF2 scintillator. The main advantage of 48Ca is that it has the highest Q-value (4.27 MeV) among all the isotope candidates for 0νββ. The CANDLES III detector is currently operating with 300kg CaF2 crystals in the Kamioka underground observatory, Japan. In 2014, a detector cooling system and a magnetic cancellation coil was installed with the aim to increase light emission of CaF2 scintillator and photo-electron collection efficiency of the photo-multipliers. After this upgrade, light yield was increased to 1000 p.e./MeV which is 1.6 times larger than before. According to data analysis and simulation, main background source in CANDLES is turned out to be high energy external gamma-ray originating neutron capture on the surrounding materials, so called (n,γ). Upgrading the detector by installing neutron and gamma-ray shield can reduce the remaining main backgrounds by two order magnitude. In this report, we discuss the detail of (n,γ) and background reduction by additional shielding

REV-ERBα Participates in Circadian SREBP Signaling and Bile Acid Homeostasis

The nuclear receptor REV-ERBα shapes the daily activity profile of Sterol Response Element Binding Protein (SREBP) and thereby participates in the circadian control of cholesterol and bile acid synthesis in the liver

Molecular Signatures Reveal Circadian Clocks May Orchestrate the Homeorhetic Response to Lactation

Genes associated with lactation evolved more slowly than other genes in the mammalian genome. Higher conservation of milk and mammary genes suggest that species variation in milk composition is due in part to the environment and that we must look deeper into the genome for regulation of lactation. At the onset of lactation, metabolic changes are coordinated among multiple tissues through the endocrine system to accommodate the increased demand for nutrients and energy while allowing the animal to remain in homeostasis. This process is known as homeorhesis. Homeorhetic adaptation to lactation has been extensively described; however how these adaptations are orchestrated among multiple tissues remains elusive. To develop a clearer picture of how gene expression is coordinated across multiple tissues during the pregnancy to lactation transition, total RNA was isolated from mammary, liver and adipose tissues collected from rat dams (n = 5) on day 20 of pregnancy and day 1 of lactation, and gene expression was measured using Affymetrix GeneChips. Two types of gene expression analysis were performed. Genes that were differentially expressed between days within a tissue were identified with linear regression, and univariate regression was used to identify genes commonly up-regulated and down-regulated across all tissues. Gene set enrichment analysis showed genes commonly up regulated among the three tissues enriched gene ontologies primary metabolic processes, macromolecular complex assembly and negative regulation of apoptosis ontologies. Genes enriched in transcription regulator activity showed the common up regulation of 2 core molecular clock genes, ARNTL and CLOCK. Commonly down regulated genes enriched Rhythmic process and included: NR1D1, DBP, BHLHB2, OPN4, and HTR7, which regulate intracellular circadian rhythms. Changes in mammary, liver and adipose transcriptomes at the onset of lactation illustrate the complexity of homeorhetic adaptations and suggest that these changes are coordinated through molecular clocks