Hyperphosphorylation of protein Tau in hippocampus may cause cognitive dysfunction of propofol-anesthetized rats.

OBJECTIVE: We aimed to explore the effect of hyperphosphorylation of Tau on cognitive function of propofol-anesthetized rats. MATERIALS AND METHODS: Thirty 2-month-old male Wistar rats weighing 180-220 g were randomly divided into 3 groups (n=10): group of treating with saline (C group), group of treating with propofol for 1 hour (P1) and 24 h (P24 group). The cognitive function of rats was tested by Morris water maze before and 1 h or 24 h after drug administration. The rats were then sacrificed. The protein and mRNA expression levels of GSK-3ß, total and phosphorylated Tau, cyclin D1, p27kip1 and c-caspase 3 in hippocampus were determined by Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. RESULTS: Compared with group C, the incubation period of P1 group and P24 group was prolonged, and the target quadrant retention time was shortened (p<0.05). There was no statistical difference between P1 and P24 group (p>0.05). Immunohistochemistry showed that compared with group C, p-Tau in hippocampus of P1 group and P24 group was highly expressed, with statistical difference (p<0.05). Western blot and RT-PCR showed that protein and mRNA expressions of GSK-3ß, phosphorylated Tau, cyclin D1 and c-caspase 3 in hippocampus of P1 and P24 groups were up-regulated (p<0.05). CONCLUSIONS: Propofol-induced cognitive dysfunction in rats may be related to the hyperphosphorylation of Tau that causes neuronal cells to re-enter the cell cycle, thus leading to apoptosis.

Cardiac hypertrophy is negatively regulated by miR-541.

Heart failure is a leading cause of death in aging population. Cardiac hypertrophy is an adaptive reaction of the heart against cardiac overloading, but continuous cardiac hypertrophy is able to induce heart failure. We found that the level of miR-541 was decreased in angiotensin II (Ang-II) treated cardiomyocytes. Enforced expression of miR-541 resulted in a reduced hypertrophic phenotype upon Ang-II treatment in cellular models. In addition, we generated miR-541 transgenic mice that exhibited a reduced hypertrophic response upon Ang-II treatment. Furthermore, we found miR-541 is the target of microphthalmia-associated transcription factor (MITF) in the hypertrophic pathway and MITF can negatively regulate the expression of miR-541 at the transcriptional levels. MITF(ce/ce) mice exhibited a reduced hypertrophic phenotype upon Ang-II treatment. Knockdown of MITF also results in a reduction of hypertrophic responses after Ang-II treatment. Knockdown of miR-541 can block the antihypertrophic effect of MITF knockdown in cardiomyocytes upon Ang-II treatment. This indicates that the effect of MITF on cardiac hypertrophy relies on the regulation of miR-541. Our present study reveals a novel cardiac hypertrophy regulating pathway that was composed of miR-541 and MITF. Modulation of their levels may provide a new approach for tackling cardiac hypertrophy.

Choline and betaine intakes are associated with reduced risk of nasopharyngeal carcinoma in adults: a case-control study.

BACKGROUND: Intakes of choline and betaine have been inversely related to the risk of various neoplasms, but scant data exist on nasopharyngeal carcinoma (NPC). We examined the association between consumption of choline and betaine and risk of NPC. METHODS: We conducted a case-control study with 600 incident NPC patients and 600 controls 1 : 1 matched by age, sex and household type in Guangdong, China. Dietary intake was assessed by a food frequency questionnaire through face-to-face interview. RESULTS: Intakes of total choline, betaine and choline+betaine were inversely related to NPC after adjustment for various lifestyle and dietary factors (all P-trend <0.001). Adjusted odds ratios (95% CI) for quartile 4 (vs quartile 1) were 0.42 (0.29, 0.61) for total choline, 0.50 (0.35, 0.72) for betaine and 0.44 (0.30, 0.64) for betaine+total choline. Regarding various sources of choline, lower NPC risk was associated with greater intakes of choline from phosphatidylcholine, free choline, glycerophosphocholine and phosphocholine, but not sphingomyelin. CONCLUSION: These findings are consistent with a beneficial effect of choline and betaine intakes on carcinogenesis.

miR-874 regulates myocardial necrosis by targeting caspase-8.

Cardiomyocyte death is an important reason for the cardiac syndromes, such as heart failure (HF) and myocardial infarction (MI). In the heart diseases, necrosis is one of the main forms of cell death. MicroRNAs (miRNAs) are a class of small non-coding RNAs that mediate post-transcriptional gene silencing. Hitherto, it is not yet clear whether miRNA can regulate necrosis in cardiomyocyte. In this work, we performed a microarray to detect miRNAs in response to H2O2 treatment, and the results showed that miR-874 was substantially increased. We further studied the function of miR-874, and observed that knockdown of miR-874 attenuated necrosis in the cellular model and also MI in the animal model. We searched for the downstream mediator of miR-874 and identified that caspase-8 was a target of miR-874. Caspase-8 was able to antagonize necrosis. When suppressed by miR-874, caspase-8 lost the ability to repress necrotic program. In exploring the molecular mechanism by which miR-874 expression is regulated, we identified that Foxo3a could transcriptionally repress miR-874 expression. Foxo3a transgenic or knockout mice exhibited a low or high expression level of miR-874, and a reduced or enhanced necrosis and MI. Our present study reveals a novel myocardial necrotic regulating model, which is composed of Foxo3a, miR-874 and caspase-8. Modulation of their levels may provide a new approach for tackling myocardial necrosis.

Direct identification of bacteria causing urinary tract infections by combining matrix-assisted laser desorption ionization-time of flight mass spectrometry with UF-1000i urine flow cytometry.

Rapid identification of bacterial pathogens from clinical specimens is essential to establish an adequate empirical antibiotic therapy to treat urinary tract infections (UTIs). We used matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) combined with UF-1000i urine flow cytometry of urine specimens to quickly and accurately identify bacteria causing UTIs. We divided each urine sample into three aliquots for conventional identification, UF-1000i, and MALDI-TOF MS, respectively. We compared the results of the conventional method with those of MALDI-TOF MS combined with UF-1000i, and discrepancies were resolved by 16S rRNA gene sequencing. We analyzed 1456 urine samples from patients with UTI symptoms, and 932 (64.0%) were negative using each of the three testing methods. The combined method used UF-1000i to eliminate negative specimens and then MALDI-TOF MS to identify the remaining positive samples. The combined method was consistent with the conventional method in 1373 of 1456 cases (94.3%), and gave the correct result in 1381 of 1456 cases (94.8%). Therefore, the combined method described here can directly provide a rapid, accurate, definitive bacterial identification for the vast majority of urine samples, though the MALDI-TOF MS software analysis capabilities should be improved, with regard to mixed bacterial infection.

Aberrant activation of the intrarenal renin-angiotensin system in the developing kidneys of type 2 diabetic rats.

We have previously reported that intrarenal angiotensin II (Ang II) levels are increased long before diabetes becomes apparent in obese Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats, a model of type 2 diabetes. In this study, we examined the changes in intrarenal renin-angiotensin system (RAS) activity in the developing kidneys of OLETF rats. Ang II contents and mRNA levels of RAS components were measured in male OLETF and control Long-Evans Tokushima (LETO) rats at postnatal days (PND) 1, 5, and 15, and at 4-30 weeks of age. In both LETO and OLETF rats, kidney Ang II levels peaked at PND 1, then decreased during the pre- and post-weaning periods. However, Ang II levels and gene expression of RAS components, including angiotensinogen (AGT), renin, and angiotensin-converting enzyme (ACE), were not significantly different between LETO and OLETF rats. Intrarenal Ang IIcontents further decreased during puberty (from 7 to 11 weeks of age) in LETO rats, bur not in OLETF rats. At 11 weeks of age, kidney Ang II levels, urinary AGT excretion, and mRNA levels of AGT and renin were higher in OLETF rats than in LETO rats, while blood glucose levels were not significantly different between these groups of rats. These data indicate that continued intrarenal expression of Ang II during pubescence contributes to the increases in intrarenal Ang II levels in prediabetic OLETF rats, and is associated with increased intrarenal AGT and renin expression. Inappropriate activation of the intrarenal RAS in the prediabetic stage may facilitate the onset and development of diabetic nephropathy in later life.

Response pattern of amino compounds in phloem and xylem of trees to soil drought depends on drought intensity and root symbiosis.

This study aimed to identify drought-mediated differences in amino nitrogen (N) composition and content of xylem and phloem in trees having different symbiotic N(2)-fixing bacteria. Under controlled water availability, 1-year-old seedlings of Robinia pseudoacacia (nodules with Rhizobium), Hippophae rhamnoides (symbiosis with Frankia) and Buddleja alternifolia (no such root symbiosis) were exposed to control, medium drought and severe drought, corresponding soil water content of 70-75%, 45-50% and 30-35% of field capacity, respectively. Composition and content of amino compounds in xylem sap and phloem exudates were analysed as a measure of N nutrition. Drought strongly reduced biomass accumulation in all species, but amino N content in xylem and phloem remained unaffected only in R. pseudoacacia. In H. rhamnoides and B. alternifolia, amino N in phloem remained constant, but increased in xylem of both species in response to drought. There were differences in composition of amino compounds in xylem and phloem of the three species in response to drought. Proline concentrations in long-distance transport pathways of all three species were very low, below the limit of detection in phloem of H. rhamnoides and in phloem and xylem of B. alternifolia. Apparently, drought-mediated changes in N composition were much more connected with species-specific changes in C:N ratios. Irrespective of soil water content, the two species with root symbioses did not show similar features for the different types of symbiosis, neither in N composition nor in N content. There was no immediate correlation between symbiotic N fixation and drought-mediated changes in amino N in the transport pathways.

Effects of carnosine on amygdaloid-kindled seizures in Sprague-Dawley rats.

The effects of carnosine (beta-alanyl-L-histidine) on amygdaloid-kindled seizures were investigated in rats. I.p. injection of carnosine (500, 1000, 1500 mg/kg, i.p.) significantly decreased seizure stage, afterdischarge duration and generalized seizure duration, and significantly prolonged generalized seizure latency of amygdaloid-kindled seizures, in a dose-dependent, and time-related manner. The protective effect of carnosine (1500 mg/kg) was completely antagonized by histamine H1-antagonists pyrilamine (2, 5 mg/kg, i.p.) and diphenhydramine (5, 10 mg/kg, i.p.), but not by histamine H2-antagonist zolantidine even at a high dose of 10 mg/kg. Carnosine (1500 mg/kg, i.p.) caused a significant increase of carnosine and histidine levels in the hypothalamus, thalamus, hippocampus, amygdala and cortex, as well as histamine levels in the hippocampus and amygdala. I.c.v. injection of alpha-fluoromethylhistidine (50 microg, i.c.v.), a selective and irreversible histidine decarboxylase inhibitor, only partially reversed the inhibition of amygdaloid-kindled seizures induced by carnosine. In addition, carnosine significantly decreased glutamate contents in the amygdala and hippocampus. These results indicate that carnosine could protect against amygdaloid-kindled seizures in rats, and its action may be due to the activation of histamine postsynaptic H1-receptors via two different mechanisms, one being carnosine's direct action, and the other being indirectly mediated by histaminergic pathway. The study suggests that carnosine may be an endogenous anticonvulsant factor in the brain and could be used as a new antiepileptic drug in the future.

Genetic control of rice blast resistance in the durably resistant cultivar Gumei 2 against multiple isolates.

To further our understanding of the genetic control of blast resistance in rice cultivar Gumei 2 and, consequently, to facilitate the utilization of this durably blast-resistant cultivar, we studied 304 recombinant inbred lines of indica rice cross Zhong 156/Gumei 2 and a linkage map comprising 181 markers. An analysis of segregation for resistance against five isolates of rice blast suggested that one gene cluster and three additional major genes that are independently inherited are responsible for the complete resistance of Gumei 2. The gene cluster was located to chromosome 6 and includes two genes mapped previously, Pi25(t), against Chinese rice blast isolate 92-183 (race ZC15) and Pi26(t) against Philippine rice blast isolate Ca89 (lineage 4), and a gene for resistance against Philippine rice blast isolate 92330-5 (lineage 17). Of the two genes conferring resistance against the Philippine isolates V86013 (lineage 15) and C923-39 (lineage 46), we identified one as Pi26(t) and mapped the other onto the distal end of chromosome 2 where Pib is located. We used three components of partial blast resistance, percentage diseased leaf area (DLA), lesion number and lesion size, all measured in the greenhouse, to measure the degree of susceptibility to isolates Ca89 and C923-39 and subsequently identified nine and eight quantitative trait loci (QTLs), respectively. Epistasis was determined to play an important role in partial resistance against Ca89. Using DLA measured on lines susceptible in a blast nursery, we detected six QTLs. While different QTLs were detected for partial resistance to Ca89 and C923-39, respectively, most were involved in the partial resistance in the field. Our results suggest that the blast resistance in Gumei 2 is controlled by multiple major genes and minor genes with epistatic effects.

Analysis on additive effects and additive-by-additive epistatic effects of QTLs for yield traits in a recombinant inbred line population of rice.

A linkage map consisting of 158 DNA markers were constructed by using a recombinant inbred line (RIL) population derived from the indica-indica rice cross Zhenshan 97B x Milyang 46. Quantitative trait loci (QTLs) conditioning grain yield and five yield component traits were determined at the one-locus and two-locus levels, and genotype-by-environment (GE) interactions were analyzed. Thirty-one QTLs were detected to have significant additive effects for yield traits, of which 12 also exhibited significant epistatic effects. Sixteen significant additive-by-additive (AA) interactions were detected, of which nine occurred between QTLs with own additive effects (M(ep)QTLs), four occurred between QTLs showing epistatic effects only (epQTLs), and three occurred between M(ep)QTLs and epQTLs. Significant GE interactions were found for six QTLs with additive effects and one AA interaction. Generally, the contributions to the phenotypic variation were higher due to QTL main effects than to epistatic effects. The detection of additive effects and AA effects of a QTL interfered with each other, indicating that the detection of QTLs with main effects, as well as the magnitude and directions of the additive effects, might vary depending on their interactions with other loci.

Hydrogen storage in single-walled carbon nanotubes at room temperature

Masses of single-walled carbon nanotubes (SWNTs) with a large mean diameter of about 1.85 nanometers, synthesized by a semicontinuous hydrogen arc discharge method, were employed for hydrogen adsorption experiments in their as-prepared and pretreated states. A hydrogen storage capacity of 4.2 weight percent, or a hydrogen to carbon atom ratio of 0.52, was achieved reproducibly at room temperature under a modestly high pressure (about 10 megapascal) for a SWNT sample of about 500 milligram weight that was soaked in hydrochloric acid and then heat-treated in vacuum. Moreover, 78.3 percent of the adsorbed hydrogen (3.3 weight percent) could be released under ambient pressure at room temperature, while the release of the residual stored hydrogen (0.9 weight percent) required some heating of the sample. Because the SWNTs can be easily produced and show reproducible and modestly high hydrogen uptake at room temperature, they show promise as an effective hydrogen storage material.

Use of Differential Rumen Fluid-Based Carbohydrate Agar Media for Culturing Lactose-Selected Cecal Bacteria from Chickens.

A rumen fluid-based differential carbohydrate agar medium for enumerating chicken cecal carbohydrate-utilizing bacteria was tested. Eleven bacteria isolated from a continuous-flow culture that had been seeded with chicken cecal contents were inoculated on fifteen different media in an anaerobic environment. These media included various levels of rumen fluid (0%, 5%, 10%, 16%) and carbohydrate (glucose [GLU], galactose [GAL], lactose[LAC]). Viable cell recovery (colony-forming units [CFU]/direct cell counts × 100%) was higher for 16% rumen fluid-supplemented carbohydrate media than the lower concentrations of rumen fluid-supplemented carbohydrate media. In addition, average viable cell recovery of all 11 bacteria on differential carbohydrate media were significantly (P < 0.05) higher in galactose and lactose media than on the glucose media. Data indicated that 16% rumen-fluid based media can be used to enumerate anaerobic, lactose-fermenting subgroups of chicken cecal bacteria.