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Abstract: Background: Chinese Tibetans have a series of distinctive physiological traits which enable them to tolerate the extreme environment of the Tibetan plateau. P-selectin gene has been proved to be highly polymorphic in Europeans and Americans. Nevertheless, studies on either the frequency distributions of single nucleotide polymorphisms (SNPs) or haplotype diversity and linkage disequilibrium of P-selectin gene in Chinese Tibetan population are still unavailable. Methods: The frequency distributions of 3 SNPs in P-selectin gene promoter (−2123C/G, −1969A/G, −1817T/C) and 3 SNPs in exon region (Ser290Asn, Val599Leu, Thr715Pro) were investigated by real-time PCR and high-resolution melting method among 314 Chinese Tibetans and 328 age- and sex-matched Han people. Results: The frequencies of the −2123G and −1817T alleles among the Tibetan population had no significant differences from those of the Han population. Among the Tibetan population, the G allele frequency of −1969A/G and Ser290Asn were both higher than those of the Han population. Val599Leu and Thr715Pro did not show any polymorphism in the two populations. In the Tibetan population, −2123C/G, −1969A/G, −1817T/C and Ser290Asn were in tight linkage disequilibrium with each other. Conclusions: The frequency distributions of −1969A/G and Ser290Asn polymorphisms in the Tibetan population were different from those in the Han population. [Copyright &y& Elsevier]

Abstract: Objective: The human papillomavirus (HPV) oncoprotein, E6, activates telomerase reverse transcriptase (TERT) expression and causes cellular immortalization. It remains unclear whether E6 affects TERT transcription by altering DNA methylation profiles. In this study, we explored the methylation status of the TERT promoter in cervical cancer cell lines and its variations after E6 was silenced by RNAi. Methods: Three kinds of cervical cell lines (HPV16 positive: CaSki and SiHa; HPV18 positive: HeLa), were taken to analyze the methylation status of the TERT promoter by methylation-specific polymerase chain reaction (MSP) and bisulfite sequencing (BS). Stealth RNAi was transiently transfected to these cell lines to silence the expression of HPV16/18 E6, and the subsequent changes of TERT mRNA levels and TERT promoter DNA methylation were examined. Results: Hypomethylation of the DNA around the TERT transcription start site (−156 to +162bp) was functionally related to its transcription. After transfection with Stealth RNAi, the levels of HPV16/18 E6 and TERT mRNA were greatly decreased. The methylated CpG around the transcription start sites in CaSki and SiHa cells were statistically increased (respectively P =0.016, P =0.000). However, there was no significant difference in HeLa cells (P =0.128). Conclusion: Hypomethylated CpG around the transcription start site enables the expression of TERT in cervical cancer cells. Our results show for the first time that HPV16 E6 can promote TERT transcription through demethylating the DNA sequence around the TERT transcription start site in cervical squamous cancer cells. [Copyright &y& Elsevier]

Abstract: Purpose: Intracerebroventricular (ICV) administration of ouabain, a potent sodium pump inhibitor, has been used to model mania. Antipsychotic agents have demonstrated efficacy in the management of acute mania. This study was undertaken to determine the prophylactic efficacy of olanzapine and haloperidol in the ouabain mania model. Methods: Male Sprague–Dawley rats (4–8/group) were treated with two haloperidol decanoate intramuscular shots one week apart (21 mg/kg) or twice daily olanzapine intraperitoneal injections at low dose (1 mg/kg/day) or high dose (6 mg/kg/day) for 7 days prior to ICV administration of ouabain. Open field locomotion was quantified at baseline and after ouabain administration. Results: Ouabain caused a significant increase in open field locomotion (253.7±SEM 55.12 vs control 53.1±12.13 squares traversed in 30 min in the olanzapine experiments, P <0.05; and 236.5±41.42 vs 129.3±38.23, P <0.05 in the haloperidol experiments). Olanzapine alone at low dose (102.2±37.7) or high dose (151.2±49.2) did not alter open field activity. Low dose olanzapine (176.6±73.27) but not high dose (307.5±167.32) caused a modest reduction of the ouabain effect. Haloperidol alone significantly reduced motoric activity compared to control (55.6±18.0, P <0.05), and prevented ouabain-induced hyperactivity (60.3±33.1, P <0.05). Conclusion: Haloperidol, but not olanzapine, demonstrated efficacy in this mania model, but methodological details may have reduced the effect of olanzapine. [Copyright &y& Elsevier]

Abstract: Cellular response to estrogen is mediated both by estrogen receptor (ER) binding to estrogen response element (ERE) and by non-nuclear actions like activation of signal transducing pathways. The main aims are to study if PI3K/Akt signaling pathway can be activated by 17β-estradiol (E2) via non-nuclear action and to investigate the relationship of the action of E2 and ER in endometrial cancer cells expressing with different status of ER. The levels of phosphorylated Akt (Ser473) (P-Akt) and total Akt were examined by western blot and Akt kinase activity was measured in cells after stimulation with 1μM E2 at different time points. Inhibitory role of LY294002 on activation of Akt induced by E2 and its estrogen antagonist, ICI182780 were also tested. P-Akt/Akt was used as a measure of activation of Akt. We found that maximum P-Akt/Akt and Akt kinase activity took place at 30min in Ishikawa cells and 15min in HEC-1A cells and the activation persisted for at least 2h after stimulation with 1μM E2. The activation of Akt elicited gradually with increasing doses of E2. PI3K inhibitor, LY294002, stopped the activating Akt in a dose-dependent manner and 50μM LY294002 completely blocked the activation of Akt induced by E2. ICI182780 could block the activation of PI3K/Akt in ER-positive Ishikawa cells but not in HEC-1A cells with poor-expressed ER. This study demonstrated that E2 is able to promptly activate PI3K/Akt signal pathway in Ishikawa cells in an ER-dependent manner and ER-independent in HEC-1A cells. Blockage of PI3K/Akt cascade may become a potential and effective way to control endometrial carcinoma, especially in ER-negative cancers, which show no response to endocrinal therapy. [Copyright &y& Elsevier]

Abstract: In investigating criminal cases of poaching and smuggling involving tigers (Panthera tigris), the number of tiger individuals involved is critical for determining the penalty. Morphological methodologies do not often work because tiger parts do not possess the distinctive characteristics of the individual. Microsatellite DNAs have been proved a reliable marker for the individualization of animals. Seven microsatellite loci derived from domestic cat (Felis catus) were selected to individualize tigers, namely F41, F42, F146, Fca304, Fca391, Fca441 and Fca453. A reference population containing 37 unrelated tigers were used to investigate alleles, allelic frequencies, genotypes and genotype frequencies of each locus. Consequently, the data was used to assess the validity of the combination of seven loci for tiger individualization. All loci were polymorphic and easy to amplify. Three out of the seven loci were significantly departure from the Hardy–Weinberg Equilibrium (P &#60; 0.05). Cumulative discrimination power (DP) calculated with observed genotype frequencies was 0.99999789. Match probability of an individual in the reference population with a random individual in seven loci ranged from 7.34 × 10−9 to 2.77 × 10−5. This suggests that combining the seven microsatellite loci provides desirable power to individualize tigers. The combination of seven loci was applied to a case of tiger bone smuggling. Genotypes of all samples were identical in all seven loci, and the P M of the evidence samples in the seven loci hit 5.63 × 10−7, provided evidence that the bones belong to a single tiger. [Copyright &y& Elsevier]

Photosynthetic light harvesting in excess light is regulated by aprocess known as feedback deexcitation. Femtosecond transient absorptionmeasurements on thylakoid membranes show selective formation of acarotenoid radical cation upon excitation of chlorophyll underconditions of maximum, steady-state feedback deexcitation. Studies ontransgenic Arabidopsis thaliana plants confirmed that this carotenoidradical cation formation is correlated with feedback deexcitation andrequires the presence of zeaxanthin, the specific carotenoid synthesizedduring high light exposure. These results indicate that energy transferfrom chlorophyll molecules to a chlorophyllzeaxanthin heterodimer, whichthen undergoes charge separation, is the mechanism for excess energydissipation during feedback deexcitation. [ABSTRACT FROM AUTHOR]

El-Mallakh RS, El-Masri MA, O'Malley Huff M, Li X-P, Decker S, Levy RS. Intracerebroventricular administration of ouabain as a model of mania in rats. Bipolar Disord 2003: 5: 362–365. © Blackwell Munksgaard, 2003 Human bipolar illness is characterized by mood state- and diagnosis-associated abnormalities of cellular cation distribution and transport. These include reduced sodium pump activity and expression and increased intracellular sodium. If these alterations are related to the pathophysiology of the disease, rather than secondary or ancillary abnormalities, then one would expect that modeling of these changes in vivo would produce lithium-preventable behavioral abnormalities. Ouabain, a potent inhibitor of the sodium pump, was administered intracerebroventricularly to male rats previously fed lithium-containing food or plain rat chow. Locomotion was then quantified in an open field. Ouabain increased locomotion 300% over baseline. Lithium pretreatment prevented the ouabain-induced hyperlocomotion response. Inhibition of central nervous system sodium pump with ouabain produces a plausible animal model of mania. This model may be useful for preclinical screening of potential mood stabilizers. [ABSTRACT FROM AUTHOR]

Equilibrium conditions of many chemical and physical processes can be determined from minimization of the Gibbs free energy of the system. Suitable closed-form representations of the Gibbs free energy and entropy of hydrogen sulfide remain unsolved in the communality of science and engineering. Here we report two suitable closed-form representations for the Gibbs free energy and entropy of hydrogen sulfide , which involve merely six molecular constants of the hydrogen sulfide molecule , whereas the conventional computation models require a great many experimental spectroscopy data. In the temperature range from 300 to 6000 K, the average relative deviations of the predicted molar Gibbs free energy and entropy values from the National Institute of Standards and Technology database are 0.185% and 0.191%, respectively. Our study presents a novel pathway of predictions of thermodynamic properties for highly toxic hydrogen sulfide. • We report two efficient closed-form representations for the Gibbs free energy and entropy of hydrogen sulfide. • Present closed-form representations only involve six molecular constants of hydrogen sulfide. • We excellently predict the molar Gibbs free energy and entropy values for hydrogen sulfide. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are evolutionarily ancient molecules that play an essential role in innate immunity across taxa from invertebrates to vertebrates. The evolution system of AMP system has not been well explained in the literature. In this study, we cloned and sequenced AMP transcriptomes of three frog species, namely Rana dybowskii, Rana amurensis, and Pelophylax nigromaculatus, which are partially sympatric in northeast Asia, but show different habitat preferences. We found that each species contained 7 to 14 families of AMPs and the diversity was higher in species with a large geographic range and greater habitat variation. All AMPs are phylogenetically related but not associated with the speciation process. Most AMP genes were under negative selection. We propose that the diversification and addition of novel functions and improvement of antimicrobial efficiency are facilitated by the expansion of family members and numbers. We also documented significant negative correlation of net charges and numbers of amino acid residues between the propiece and mature peptide segments. This supports the Net Charge Balance Hypothesis. We propose the Cut Point Sliding Hypothesis as a novel diversification mechanism to explain the correlation in lengths of the two segments. [ABSTRACT FROM AUTHOR]

Epidemiological studies have demonstrated that type 2 diabetes mellitus (T2DM) and hyperinsulinemia are associated closely with endometrial carcinoma risk, although the molecular mechanism remains unclear. Insulin receptor isoformA expression is upregulated in many cancer cells and tissues, which suggests that IR-A-mediated signaling pathways may have important implications for cancer pathogenesis. We measured the expression of insulin receptor isoforms (IR-A and IR–B in the normal endometrium tissues, the endometrial carcinoma tissues and the endometrial carcinoma cell lines. We found that the total insulin receptor (IR) and IR-A expression mRNA levels and the ratio of IR-A to total IR in endometrial carcinoma specimens were significantly higher than them in control endometrial tissue specimens(P<0.05). Further analysis indicated that the tendency was more prominently in patients with T2DM. IR-A mRNA was differentially expressed in four endometrial carcinoma cell lines (Ishikawa, KLE, RL95-2 and HEC-1-A. RL95-2 cells have a low endogenous IR-A expression, and these were used to construct a stable cell line overexpressing IR-A. We found that IR-A overexpression significantly increased cell proliferation, the proportion of cells in S phase, activation of the Akt pathway and tumorigenicity of xenografts in nude mice. In contrast, there was no significant difference in the the percentage of apoptotic cells between cells overexpressing IR-A and control cells. Moreover, levels of phosphorylated ERK1/2 protein were significantly decreased in cells overexpressing IR-A relative to controls. These findings reveal the pivotal role of IR-A in endometrial cancer carcinogenesis, and suggest that the association of elevated IR-A levels with cell proliferation and tumorigenicity may be causally linked to its effect on the proportion of cells in S phase and the activation of the Akt pathway. [ABSTRACT FROM AUTHOR]