Effects of alternate phases of fish oil and vegetable oil-based diets in Murray cod

Fish oil (FO)- and canola oil (CO)-based diets were regularly alternated in a daily cycle (amCO: alternation of CO in the morning and FO in the afternoon, and pmCO: alternation of FO in the morning and CO in the afternoon) or in a series of weekly cycles (2W: alternation of 2 weeks on CO and 2 weeks on FO, 4W: alternation of 4 weeks on CO and 4 weeks on FO), over a 16-week period in juvenile Murray cod (Maccullochella peelii peelii). No significant differences were observed between any of the treatments in relation to the final weight. However, fish subjected to the 2W schedule were larger (P>0.05) than all other treatments (37.2 ± 0.30 vs. 34.3 ± 0.58 in the control treatment). Fish receiving the 2W treatment had a significantly lower total net disappearance of eicosapentaenoic acid 20:5n-3 (EPA) and docosahexaenoic acid 22:6n-3 (62.1% and 24.0% respectively) compared with the control treatment (fish continuously fed a blend of 50% FO and 50% CO). Likewise, Murray cod receiving the amCO daily schedule had a significantly lower total net disappearance of EPA in comparison with the CD and pmCO treatments. These data point towards the existence of cyclical mechanisms relative to fatty acid utilization/retention.

Studies of the human lymphocyte P2Z receptor and its activation of phospholipase D

Extracellular adenosine 5′-triphosphate (ATP) is an agonist for the P2Z receptor of human leukaemic lymphocytes and opens a Ca ²⁺-selective ion channel, which also conducts Ba²⁺, Sr²⁺ and the small fluorescent dye, ethidium⁺. A wide range of receptor agonists, many of which raise cytosolic [Ca²⁺] activate phospholipase D (PLD). In the present study, it was shown that both ATP and 3′-O-(4-benzoylbenzoyl)-ATP (BzATP) stimulated PLD activity in a concentration-dependent manner, and the inhibitory effects of suramin, oxidised ATP, extracellular Na⁺ and Mg²⁺ suggested that the effect of these agonists is mediated by P2Z receptors. The role of divalent cations in ATP-stimulated PLD activity was investigated. Several agonists (eg ATP, thapsigargin, ionomycin) stimulated a rise in cytosolic [Ca²⁺] in human lymphocytes, but only ATP and ionomycin stimulated PLD activity. When Ca²⁺ influx was prevented by EGTA, the majority of ATP-stimulated and all of ionomycin-stimulated PLD activity was inhibited. Preloading cells with the Ca²⁺ chelator, BAPTA, reduced cytosolic [Ca²⁺] and, paradoxically, ATP-stimulated PLD activity was potentiated. ATP-stimulated PLD activity was supported by both Ba²⁺ and Sr²⁺ when they were substituted for extracellular Ca²⁺. Furthermore, both ATP-stimulated PLD activity and ATP-stimulated ¹³³Ba²⁺ influx showed a linear dependence on extracellular [Ba²⁺]. Thus it was concluded that ATP stimulated PLD activity in direct proportion to the influx of divalent cations through the P2Z ion channel and this PLD activity was insensitive to changes in bulk cytosolic [Ca²⁺]. The calmodulin (Ca²⁺/CaM) inhibitor, trifluoperazine (TFP) inhibited ionomycin- and ATP-stimulated PLD activity and ATP-stimulated apoptosis, but had no effect on PLD activity already activated by ATP. However, TFP inhibited ATP-stimulated Ca²⁺, Ba²⁺ and ethidium⁺ fluxes, at concentrations below those which inhibit Ca²⁺/CaM, suggesting that TFP inhibits the P2Z receptor. Similarly, the isoquinolinesulphonamide, KN-62, a selective inhibitor of Ca²⁺/CaM-dependent protein kinase II (CaMKII), also prevented ATP-stimulated apoptosis, but had no effect on pre-activated PLD. In addition, KN-62, and an analogue, KN-04, which has no effect on CaMKII, potently inhibited ATP-stimulated Ba²⁺ influx (IC₅₀ 12.7 ± 1.5 and 17.3 ± 2.7 nM, respectively), ATP-stimulated ethidium⁺ uptake (IC₅₀ 13.1 ± 2.6 and 37.2 ± 8.9 nM, respectively), ATP-stimulated phospholipase D activity (50% inhibition 5.9 ± 1.2 and 9.7 ± 2.8 nM, respectively) and ATP-induced shedding of the surface adhesion molecule, L-selectin (IC₅₀ 31.5 ± 4.5 and 78.7 ± 10.8 nM, respectively). They did not inhibit phorbol ester- or ionomycin-stimulated PLD activity or phorbol ester-induced L-selectin shedding. Neither KN-62 nor KN-04 (both 500 nM) have any effect on UTP-stimulated Ca²⁺ transients in fura-2-loaded human neutrophils, a response which is mediated by the P2Y₂ receptor, neither did they inhibit ATP-stimulated contractile responses mediated by the P2X₁ receptor of guinea pig urinary bladder. Thus, KN-62 and KN-04 are almost equipotent as P2Z inhibitors with IC₅₀s in the nanomolar, indicating that their actions cannot be due to CaMKII inhibition, but rather that they are potent and direct inhibitors of the P2Z receptor. Extracellular ATP-induced shedding of L-selectin from lymphocytes into the medium is a Ca²⁺-independent response. L-selectin is either cleaved by a metalloproteinase or a PLD with specificity for glycosylphosphatidylinositol (GPI). The novel hydroxamic acid-based zinc chelator, Ro-31-9790 blocks ATP-induced L-selectin shedding, but was without effect on ATP-induced Ba²⁺ influx or ATP-stimulated PLD activity. Furthermore, another zinc chelator, 1,10-phenanthroline, an inhibitor of a GPI-PLD, potentiated rather than inhibited ATP-stimulated PLD activity, suggesting that ATP-induced L-selectin shedding and ATP-stimulated PLD activity are independent of each other. Although extracellular ATP is the natural ligand for the lymphocyte P2Z receptor, it is less potent than BzATP in stimulating Ba²⁺ influx. Concentration-response curves for BzATP- and ATP-stimulated ethidium⁺ influx gave EC₅₀s 15.4 ± 1.4 µM and 85.6 ± 8.8 µM, respectively. The maximal response to ATP was only 69.8 ± 1.9% of that for BzATP. Hill coefficients were 3.17 ± 0.24 and 2.09 ± 0.45 for BzATP and ATP respectively, suggesting greater positive cooperativity for BzATP than for ATP in opening the P2Z-operated ion channel. A rank order of agonist potency of BzATP > ATP = 2MeSATP > ATPγS was observed for agonist-stimulated ethidium⁺ influx, while maximal influxes followed a rank order of BzATP > ATP > 2MeSATP > ATPγS. When ATP (300 -1000 µM) was added simultaneously with 30 µM BzATP (EC₉₀), it reduced both ethidium⁺ and Ba²⁺ fluxes by 30 - 40% relative to values observed with BzATP alone. KN-62, previously shown to be a specific inhibitor of the lymphocyte P2Z receptor, was a less potent antagonist of BzATP-induced fluxes than ATP, when maximal concentrations of both agonists (50 and 500 µM respectively) were used. However, when BzATP (18 µM) was used at a concentration equiactive with a maximally effective ATP concentration, KN-62 showed the same inhibitory potency for both agonists. The ecto-ATPase antagonist, ARL-67156, inhibited both ATP- and BzATP-stimulated Ba²⁺ influx, suggesting that the lower efficacy of ATP compared with BzATP was not due to preferential hydrolysis of ATP. Thus, the natural ligand, ATP, is a partial agonist for the P2Z receptor while BzATP is a full agonist. Moreover the competitive studies show that only a single class of P2-receptor (P2Z class) is expressed on human leukaemic lymphocytes. Both ATP- and BzATP-stimulated PLD activity were significantly inhibited (P < 0.05) when cells were suspended in iso-osmotic choline Cl medium. Choline⁺ was found to be a permeant for the P2Z ion channel, since ATP induced a large uptake of [¹⁴C]choline⁺ (60 to 150 µmol/ml intracellular water) during a 5 min incubation, which remained in the cells for several hours, and ATP was used to load cells with these levels of choline⁺. Intracellular choline⁺ inhibited ATP-, BzATP-, PMA- and ionomycin-stimulated PLD activity. Brief exposure of lymphocytes to ATP increased the subsequent basal rate of ethidium⁺ uptake, and this was prevented by intracellular choline⁺. It is proposed that P2Z-mediated Ca²⁺ influx in lymphocytes activates PLD leading to significantly changes of the phospholipid composition of the plasma membrane, which subsequently produces a permeability lesion, which in turn contributes to cell death.

Comparative studies of structural transition between AlN nanocrystals and nanowires

The structural transition of AIN nanocrystals and nanowires were investigated simultaneously under pressures up to 37.2 GPa by in situ angle dispersive high-pressure x-ray diffraction using synchrotron radiation source and a single diamond anvil cell. The size of hexagonal AIN nanocrystals and the diameter of nanowires are 45 nm on average. A pressure-induced wurtzite to rocksalt phase transition starts at 21.5 GPa and completes at 27.8 GPa for the nanocrystals and nanowires, respectively. The high-pressure behaviors of AlN nanocrystals the same as the AIN nanowires might arise from the similar size and diameter in nanocrystals and nanowires. Hexagonal AIN nanocrystals (45 nm) display an apparent volumetric contraction as compared to the AlN nanocrystals (10 nm) which might induce the difference of transition pressure.

Assessment of a six-week computer-based remediation program for social cognition in chronic schizophrenia

Background: Programs to remediate cognitive deficits have shown promising results in schizophrenia, but remediation of social cognition deficits is less well understood. Social cognitive deficits may cause more disability than the widely recognized neurocognitive deficits, suggesting that this is an area worthy of further investigation. Aim: Implement and evaluate a brief computerized cognitive remediation program designed to improve memory, attention, and facial affect recognition (FAR) in outpatients with chronic schizophrenia.

Methods: Baseline assessments of FAR and of clinical, cognitive, and psychosocial functioning were completed on 20 males with schizophrenia enrolled in an outpatient rehabilitation program at the Shanghai Mental Health Center (the intervention group) and on 20 males with schizophrenia recruited from among regular outpatients at the Center (the control group). Both groups received treatment as usual, but the intervention group also completed an average of 12.7 sessions of a computer-based remediation program for neurocognitive, social, and FAR functioning over a 6-week period. The baseline measures were repeated in both groups at the end of the 6-week trial.

Results: There were no statistically significant differences in the changes in clinical symptoms (assessed by the Positive and Negative Syndrome Scale, PANSS) or cognitive measures (assessed using the Hong Kong List Learning Test and the Letter-Number Sequencing Task) between the intervention and control groups over the 6-week trial, but there were modest improvements on the PANSS for the intervention group between baseline and after the intervention. There was a significantly greater improvement in the social functioning measure (the Personal and Social Performance scale, PSP) in the intervention group than in the control group. The pre-post change in the total facial recognition score in the intervention group was statistically significant (paired t-test=-2.60, p=0.018), and there was a statistical trend of a greater improvement in facial recognition in the intervention group than in the control group (F(1,37)=2.93; p=0.092).

Conclusions: Integration of FAR training with a short, computer-administrated cognitive remediation program may improve recognition of facial emotions by individuals with schizophrenia, and, thus, improve their social functioning. But more work on developing the FAR training modules and on testing them in larger, more diverse samples will be needed before this can be recommended as a standard part of cognitive remediation programs.