LIN Group Research Articles

The key role of ubiquitination and sumoylation in signaling and cancer: a research topic

EDITORIAL article Front. Oncol., 05 December 2012 | https://doi.org/10.3389/fonc.2012.00187

PI3Kγ Is Required for PDE4, not PDE3, Activity in Subcellular Microdomains Containing the Sarcoplasmic Reticular Calcium ATPase in Cardiomyocytes

We recently showed that phosphoinositide-3-kinase-gamma-deficient (PI3Kgamma(-/-)) mice have enhanced cardiac contractility attributable to cAMP-dependent increases in sarcoplasmic reticulum (SR) Ca(2+) content and release but not L-type Ca(2+) current (I(Ca,L)), demonstrating PI3Kgamma locally regulates cAMP levels in cardiomyocytes. Because phosphodiesterases (PDEs) can contribute to cAMP compartmentation, we examined whether the PDE activity was altered by PI3Kgamma ablation. Selective inhibition of PDE3 or PDE4 in wild-type (WT) cardiomyocytes elevated Ca(2+) transients, SR Ca(2+) content, and phospholamban phosphorylation (PLN-PO(4)) by similar amounts to levels observed in untreated PI3Kgamma(-/-) myocytes. Combined PDE3 and PDE4 inhibition caused no further increases in SR function. By contrast, only PDE3 inhibition affected Ca(2+) transients, SR Ca(2+) loads, and PLN-PO(4) levels in PI3Kgamma(-/-) myocytes. On the other hand, inhibition of PDE3 or PDE4 alone did not affect I(Ca,L) in either PI3Kgamma(-/-) or WT cardiomyocytes, whereas simultaneous PDE3 and PDE4 inhibition elevated I(Ca,L) in both groups. Ryanodine receptor (RyR(2)) phosphorylation levels were not different in basal conditions between PI3Kgamma(-/-) and WT myocytes and increased in both groups with PDE inhibition. Our results establish that L-type Ca(2+) channels, RyR(2), and SR Ca(2+) pumps are regulated differently in distinct subcellular compartments by PDE3 and PDE4. In addition, the loss of PI3Kgamma selectively abolishes PDE4 activity, not PDE3, in subcellular compartments containing the SR Ca(2+)-ATPase but not RyR(2) or L-type Ca(2+) channels.

Dimensions of Guanxi in Chinese Elite Politics

Scholars of Communist Party recognize critical influences of guanxi on political behaviour. Lowell Dittmer, for example, argues that guanxi is the central term in our conceptualization of in China. Lowell Dittmer, Chinese Informal China Journal, No. 34 (July 1995), p. 10. Hans J. van de Ven identifies intense personal relationships in party cells during period when Party was born. Hans J. van de Ven, The Emergence of Text-Centered Party, in Tony Saich and Hans van de Ven (eds), New Perspectives on Communist Revolution (New York: M. E. Sharpe, 1995), p. 9. Zhang Guotao specified guanxi as primary force that ensured Party's survival when nationalists and Communists split from United Front in 1920s. See William W. Whitson with Chen-hsia Huang, High Command: A History of Communist Military Politics, 1927-1971 (New York: Praeger, 1973), p. 50. Other studies of CCP confirm pervasiveness of these interpersonal influences after founding of People's Republic. Li Rui's memoirs indicate important role of guanxi in pursuing political advantages and mutual protection in 1959 Lushan Plenum. Li Rui, Lushan huiyi shilu (True Record of Lushan Conference) (Zhengzhou: Henan Renmin Chubanshe, 1995), pp. 34, 74, 169, 280. Frederick C. Teiwes and Warren Sun deem personal ties an important factor in determining alignments of Party elite during Cultural Revolution. An excellent analysis is their in-depth examination of Lin Biao case, in which strong professional and personal ties played a significant role in bonding Lin's group together. Frederick C. Teiwes and Warren Sun, Tragedy of Lin Biao (London: Hurst and Company, 1996), pp. 38-42. In investigating elite politics during post-Mao period, Richard Baum sees zongpai (factions) as a decisive factor in politics and a source of significant irregularity in reform cycles. Baum defines zongpai as informal networks of

Effects of dietary vegetable oil inclusion and composition on the susceptibility of pig meat to oxidation

AbstractThis investigation was designed to evaluate the effects of the dietary inclusion of vegetable oil and its composition on fatty acid composition and lipid oxidation in pig muscle. Pigs were given the following diets from 50 kg to slaughter (90 kg): a control diet with no added fat (NF) or diets containing 20 g/kg of sunflower (SUN), olive (OL) or sunflower + linseed (SUN + LIN) oils. Meat from pigs given the SUN + LIN diet showed the highest thiobarbituric acid reactive substances (TBARS) from day 3 of refrigerated storage to the end of the experiment (P< 0·05). The OL group showed the lowest TBARS after 9 days of storage (P< 0·05). Pigs on NF showed intermediate values that were generally closer to those recorded for pigs given the SUN + LIN than the OL diet. By day 9, there was no statistical difference between the NF and the SUN + LIN group. The SUN group also showed intermediate TBARS throughout storage, with no statistical differences compared with the NF group. After 9 days of storage the lowest CIELAB a* value, corresponded to the SUN + LIN group and the highest to the OL group. These results indicate similar behaviour to that of lipid oxidation. Meat samples from pigs given the diet not enriched with fat showed greater drip loss than those given the remaining diets (P< 0·05) while there was no significant effect of dietary fat source on water-holding capacity. The inclusion of oils rich in linoleic fatty acids in pig diets modifies muscle fatty acid composition but susceptibility to lipid oxidation does not appear to be increased with respect to that occurring in pigs given diets with no added fat.

Effect of Dietary Fat on the Response of the Rat Retina to Chronic and Acute Light Stress

We designed an experiment to study the role of light history and polyunsaturated fatty acids (PUFA) on the susceptibility of the albino rat retina to light damage. Albino rats were born to dams that had been kept in either 1 lx or 250 lx cyclic light for 0-4 days prior to delivery and fed one of three diets containing either 10% (by weight) hydrogenated coconut oil (COC, no n-3 nor n-6 fatty acids), safflower oil (SAF, high n-6, < 0.1% n-3 fatty acids), or linseed oil (LIN, high n-3, low n-6 fatty acids). After weaning, the rats were maintained in the same light environment and fed the same diets for 9 weeks, at which time some were killed and their retinas processed for morphometric analysis. Animals raised in bright cyclic light had shorter ROS lengths and thinner outer nuclear layers (ONL) than rats raised in dim cyclic light. The LIN animals had a thinner ONL than animals of the SAF or COC groups. Rats from each diet and light rearing groups were exposed to constant illumination of 2000 lx for 24 hr, after which they and non-exposed controls were placed in 1 lx cyclic light for 10 days and analysed for changes in ONL thickness. In the 250 lx (bright; B) groups, there was no effect of acute light stress on ONL thickness, although both control and stressed LIN animals had a thinner ONL than the corresponding COC and SAF groups. However, in the rats raised in 1 lx cyclic light, acute stress resulted in significant retinal damage (i.e. decrease in ONL thickness) in the three diet groups combined. The superior region was damaged the most and the severity was dependent on diet, as evidenced by the LIN group having a greater reduction in ONL thickness than the SAF group after light stress. From these results we conclude that rats on diets high in n-3 fatty acids are more susceptible to photoreceptor cell loss than animals fed n-6 or no polyunsaturated fatty acids when raised in dim cyclic light. These results show that both diet and light history play a role in the susceptibility of the retina to acute and chronic effects of light and suggest a role for lipid peroxidation in retinal light damage.

Effect of dietary fat and environmental lighting on the phospholipid molecular species of rat photoreceptor membranes

We have previously shown that retinas of albino rats adapt to bright cyclic light (500-800 lx) by lowering the levels of docosahexaenoic acid (22:6n-3) in their rod outer segment (ROS) phospholipids. In the present study, we addressed the role of dietary fat in this process. Pregnant rats were kept in 1 lx or 250 lx cyclic illuminance (12L:12D) and fed diets containing 10% (by weight) of either hydrogenated coconut oil (COC, no n-3 or n-6 fatty acids), linseed oil (LIN, n-3 and n-6 fatty acids), or safflower oil (SAF, only n-6 fatty acids), starting 4 days before delivery. Pups were weaned at 3 weeks of age and continued on the same diet and light regime. At 12 weeks of age, 3 or 4 animals in each diet-light group were killed and the remaining animals were stressed continuously with 2000 lx light for 24 hr and then kept in 1 lx cyclic light for 10 days. Fatty acids and phospholipid molecular species (PLMS) of ROS membranes were determined. For prestressed groups, those animals fed the LIN diet had high levels of 22:6n-3 and PLMS containing 22:6n-3, with little 22:5n-6. Compared to the LIN group, the COC and SAF groups had lower levels of 22:6n-3- and 22:6n-3)-containing PLMS and higher levels of 22:5n-6 and molecular species containing 22:5n-6, such as 22:5n-6/22:6n-3, 16:0/22:5n-6 and 18:0/22:5n-6. Within each dietary group, animals raised in 250 lx cyclic illuminance had lower levels of 22:6n-3 and 22:5n-6 compared to those raised at 1 lx. This light effect was greater for 22:6n-3 in the LIN group than for 22:5n-6 in the SAF group. After the acute light stress, those animals raised in 1 lx showed dramatic reduction in PLMS containing 22:6n-3 and 22:5n-6, especially polyenoic species such as 22:6n-3/22:6n-3 in the LIN group and 22:5n-6/22:6n-3 in the COC and SAF groups. In contrast, animals raised in 250 lx showed much smaller changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of dietary fat on the response of the rat retina to chronic and acute light stress

We designed an experiment to study the role of light history and polyunsaturated fatty acids (PUFA) on the susceptibility of the albino rat retina to light damage. Albino rats were born to dams that had been kept in either 1 lx or 250 lx cyclic light for 0-4 days prior to delivery and fed one of three diets containing either 10% (by weight) hydrogenated coconut oil (COC, no n-3 nor n-6 fatty acids), safflower oil (SAF, high n-6, < 0.1% n-3 fatty acids), or linseed oil (LIN, high n-3, low n-6 fatty acids). After weaning, the rats were maintained in the same light environment and fed the same diets for 9 weeks, at which time some were killed and their retinas processed for morphometric analysis. Animals raised in bright cyclic light had shorter ROS lengths and thinner outer nuclear layers (ONL) than rats raised in dim cyclic light. The LIN animals had a thinner ONL than animals of the SAF or COC groups. Rats from each diet and light rearing groups were exposed to constant illumination of 2000 lx for 24 hr, after which they and non-exposed controls were placed in 1 lx cyclic light for 10 days and analysed for changes in ONL thickness. In the 250 lx (bright; B) groups, there was no effect of acute light stress on ONL thickness, although both control and stressed LIN animals had a thinner ONL than the corresponding COC and SAF groups. However, in the rats raised in 1 lx cyclic light, acute stress resulted in significant retinal damage (i.e. decrease in ONL thickness) in the three diet groups combined. The superior region was damaged the most and the severity was dependent on diet, as evidenced by the LIN group having a greater reduction in ONL thickness than the SAF group after light stress. From these results we conclude that rats on diets high in n-3 fatty acids are more susceptible to photoreceptor cell loss than animals fed n-6 or no polyunsaturated fatty acids when raised in dim cyclic light. These results show that both diet and light history play a role in the susceptibility of the retina to acute and chronic effects of light and suggest a role for lipid peroxidation in retinal light damage.