[Study on the Temperature Dependent Phase Transformation of Raman Spectra for Cyclobutanol].

Cyclobutanol (C4H8O) is one of the four-membered ring type molecules, which usually adopts a non-planar equilibrium conformation, and the substituent group OH can adopt two positions relative to the puckered ring, the axial or the equatorial, giving rise to an additional degree of freedom and various molecular conformations. Additionally, temperature is one important thermodynamic parameter that greatly influents the structure and induces the possibility of conformational change or crystal change. As a consequence, there may be a number of phase transitions and molecular conformations for cyclobutanol under different temperature. In this paper, Raman and infrared spectroscopic technique were applied to investigate the vibration modes of cyclobutanol. The results indicate that the main component of the liquid cyclobutanol is equatorial-trans (Eq-t) conformer with a few Eq-g conformers at ambient condition. Then differential scanning calorimetry (DSC) and low temperature Raman spectroscopic were applied to study the phase transition of cyclobutanol during the cooling and heating process. It is observed that the Raman spectra and the intensities of these bands are not significantly changed during the cooling process. The results indicate that there is sill no presence of solidification especially cooling to 140K, which indicates that the cyclobutanol still remains the liquid state and supercooled state is observed during the cooling process. And this supercooled liquid is one metastable state, not in thermodynamic equilibrium. Further cooling to 138 K, the super-cooling liquid cyclobutanol will transform into the glassy state, accompanied with a small change of entropy. During the heating process, as the temperature is raised to 180 K, the Raman peaks became sharper and some new characteristic peaks appeared abruptly and a discontinuous change was observed in bandwidths versus temperature. And these new signatures can be maintained upon to 220 K, and then will disappear as the temperature increasing continuously. This result indicates the one crystal phase transition and a melting transition present at around 180 and 220 K. In addition, it can be observed that the component of Eq-g conformer increases, accompanied with the crystallization during heating at around 180 K. These results were helpful to understand the kinetics of the crystallization process of other small organic molecules.

Tolbutamide controls glucagon release from mouse islets differently than glucose: involvement of K(ATP) channels from both α-cells and δ-cells.

We evaluated the role of ATP-sensitive K⁺ (K(ATP)) channels, somatostatin, and Zn²âº in the control of glucagon secretion from mouse islets. Switching from 1 to 7 mmol/L glucose inhibited glucagon release. Diazoxide did not reverse the glucagonostatic effect of glucose. Tolbutamide decreased glucagon secretion at 1 mmol/L glucose (G1) but stimulated it at 7 mmol/L glucose (G7). The reduced glucagon secretion produced by high concentrations of tolbutamide or diazoxide, or disruption of K(ATP) channels (Sur1(-/-) mice) at G1 could be inhibited further by G7. Removal of the somatostatin paracrine influence (Sst(-/-) mice or pretreatement with pertussis toxin) strongly increased glucagon release, did not prevent the glucagonostatic effect of G7, and unmasked a marked glucagonotropic effect of tolbutamide. Glucose inhibited glucagon release in the absence of functional K(ATP) channels and somatostatin signaling. Knockout of the Zn²âº transporter ZnT8 (ZnT8(-/-) mice) did not prevent the glucagonostatic effect of glucose. In conclusion, glucose can inhibit glucagon release independently of Zn²âº, K(ATP) channels, and somatostatin. Closure of K(ATP) channels controls glucagon secretion by two mechanisms, a direct stimulation of α-cells and an indirect inhibition via somatostatin released from δ-cells. The net effect on glucagon release results from a balance between both effects.

Mechanisms of control of the free Ca2+ concentration in the endoplasmic reticulum of mouse pancreatic ß-cells: interplay with cell metabolism and [Ca2+]c and role of SERCA2b and SERCA3.

OBJECTIVE: Sarco-endoplasmic reticulum Ca(2+)-ATPase 2b (SERCA2b) and SERCA3 pump Ca(2+) in the endoplasmic reticulum (ER) of pancreatic ß-cells. We studied their role in the control of the free ER Ca(2+) concentration ([Ca(2+)](ER)) and the role of SERCA3 in the control of insulin secretion and ER stress. RESEARCH DESIGN AND METHODS: ß-Cell [Ca(2+)](ER) of SERCA3(+/+) and SERCA3(-/-) mice was monitored with an adenovirus encoding the low Ca(2+)-affinity sensor D4 addressed to the ER (D4ER) under the control of the insulin promoter. Free cytosolic Ca(2+) concentration ([Ca(2+)](c)) and [Ca(2+)](ER) were simultaneously recorded. Insulin secretion and mRNA levels of ER stress genes were studied. RESULTS: Glucose elicited synchronized [Ca(2+)](ER) and [Ca(2+)](c) oscillations. [Ca(2+)](ER) oscillations were smaller in SERCA3(-/-) than in SERCA3(+/+) ß-cells. Stimulating cell metabolism with various [glucose] in the presence of diazoxide induced a similar dose-dependent [Ca(2+)](ER) rise in SERCA3(+/+) and SERCA3(-/-) ß-cells. In a Ca(2+)-free medium, glucose moderately raised [Ca(2+)](ER) from a highly buffered cytosolic Ca(2+) pool. Increasing [Ca(2+)](c) with high [K] elicited a [Ca(2+)](ER) rise that was larger but more transient in SERCA3(+/+) than SERCA3(-/-) ß-cells because of the activation of a Ca(2+) release from the ER in SERCA3(+/+) ß-cells. Glucose-induced insulin release was larger in SERCA3(-/-) than SERCA3(+/+) islets. SERCA3 ablation did not induce ER stress. CONCLUSIONS: [Ca(2+)](c) and [Ca(2+)](ER) oscillate in phase in response to glucose. Upon [Ca(2+)](c) increase, Ca(2+) is taken up by SERCA2b and SERCA3. Strong Ca(2+) influx triggers a Ca(2+) release from the ER that depends on SERCA3. SERCA3 deficiency neither impairs Ca(2+) uptake by the ER upon cell metabolism acceleration and insulin release nor induces ER stress.

Tissue-specific disallowance of housekeeping genes: the other face of cell differentiation.

We report on a hitherto poorly characterized class of genes that are expressed in all tissues, except in one. Often, these genes have been classified as housekeeping genes, based on their nearly ubiquitous expression. However, the specific repression in one tissue defines a special class of "disallowed genes." In this paper, we used the intersection-union test to screen for such genes in a multi-tissue panel of genome-wide mRNA expression data. We propose that disallowed genes need to be repressed in the specific target tissue to ensure correct tissue function. We provide mechanistic data of repression with two metabolic examples, exercise-induced inappropriate insulin release and interference with ketogenesis in liver. Developmentally, this repression is established during tissue maturation in the early postnatal period involving epigenetic changes in histone methylation. In addition, tissue-specific expression of microRNAs can further diminish these repressed mRNAs. Together, we provide a systematic analysis of tissue-specific repression of housekeeping genes, a phenomenon that has not been studied so far on a genome-wide basis and, when perturbed, can lead to human disease.

[Preparation and luminescence of Eu3+ /Yb3+ codoped ZrO2 powders].

Samples of Eu3+ /Yb3+ co-doped ZrO2 powders were prepared by co-precipitation method. The dependence on the sintering temperature and doping concentration of the structure and luminescence was studied. The results confirmed that the sintering temperature has significant influence on the crystalline phases of ZrO2. As the sintering temperature increased the tetragonal phase was transformed into monoclinic phase. After sintered at 1150 degrees C, single monoclinic phase was observed. In contrast, with the increase in the doping concentration of Yb3+, the crystalline phase was also changed, and the monoclinic phase was transformed back to tetragonal phase. With 1% Eu3+ and 10% Yb3+ doping, single tetragonal phase presents. It was observed that the luminescent properties of Eu3+ ions in two structures were different. Experiment results reveal that the luminescence can be affected by both sintering temperature and doping concentration. With single Yb3+ doping, no NIR emission was observed under ultraviolet light excitation (270 nm). However, with Eu3+/Yb3+ codoping, NIR emission around 980 nm from Yb3+ ((2)F(5/2)-->(2)F(7/2)) was observed under the same excitation. Furthermore, it is confirmed that Yb3+ has the same excitation spectrum with Eu3+. This down-conversion result indicates that there is an energy transfer process between Eu3+ and Yb3+. Cooperative energy transfer process and cross-relaxation process were assigned as the possible mechanism for the near-infrared emission of Yb3+.

Glucose and pharmacological modulators of ATP-sensitive K+ channels control [Ca2+]c by different mechanisms in isolated mouse alpha-cells.

OBJECTIVE: We studied how glucose and ATP-sensitive K(+) (K(ATP)) channel modulators affect alpha-cell [Ca(2+)](c). RESEARCH DESIGN AND METHODS: GYY mice (expressing enhanced yellow fluorescent protein in alpha-cells) and NMRI mice were used. [Ca(2+)](c), the K(ATP) current (I(KATP), perforated mode) and cell metabolism [NAD(P)H fluorescence] were monitored in single alpha-cells and, for comparison, in single beta-cells. RESULTS: In 0.5 mmol/l glucose, [Ca(2+)](c) oscillated in some alpha-cells and was basal in the others. Increasing glucose to 15 mmol/l decreased [Ca(2+)](c) by approximately 30% in oscillating cells and was ineffective in the others. alpha-Cell I(KATP) was inhibited by tolbutamide and activated by diazoxide or the mitochondrial poison azide, as in beta-cells. Tolbutamide increased alpha-cell [Ca(2+)](c), whereas diazoxide and azide abolished [Ca(2+)](c) oscillations. Increasing glucose from 0.5 to 15 mmol/l did not change I(KATP) and NAD(P)H fluorescence in alpha-cells in contrast to beta-cells. The use of nimodipine showed that L-type Ca(2+) channels are the main conduits for Ca(2+) influx in alpha-cells. gamma-Aminobutyric acid and zinc did not decrease alpha-cell [Ca(2+)](c), and insulin, although lowering [Ca(2+)](c) very modestly, did not affect glucagon secretion. CONCLUSIONS: alpha-Cells display similarities with beta-cells: K(ATP) channels control Ca(2+) influx mainly through L-type Ca(2+) channels. However, alpha-cells have distinct features from beta-cells: Most K(ATP) channels are already closed at low glucose, glucose does not affect cell metabolism and I(KATP), and it slightly decreases [Ca(2+)](c). Hence, glucose and K(ATP) channel modulators exert distinct effects on alpha-cell [Ca(2+)](c). The direct small glucose-induced drop in alpha-cell [Ca(2+)](c) contributes likely only partly to the strong glucose-induced inhibition of glucagon secretion in islets.

The GluCre-ROSA26EYFP mouse: a new model for easy identification of living pancreatic alpha-cells.

The control of glucagon secretion by pancreatic alpha-cells is poorly understood, largely because of the difficulty to recognize living alpha-cells. We describe a new mouse model, referred to as GluCre-ROSA26EYFP (or GYY), allowing easy alpha-cell identification because of specific expression of EYFP. GYY mice displayed normal glycemic control during a fasting/refeeding test or intraperitoneal insulin injection. Glucagon secretion by isolated islets was normally inhibited by glucose and stimulated by adrenaline. [Ca(2+)](c) responses to arginine, adrenaline, diazoxide and tolbutamide, were similar in GYY and control mice. Hence, this new mouse model is a reliable and powerful tool to specifically study alpha-cells.