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We explored the protective mechanisms of human neuronal mitochondrial uncoupling protein-5 (UCP5) in MPP+- and dopamine-induced toxicity after its stable overexpression in SH-SY5Y cells. We raised specific polyclonal antibodies. Overexpressed UCP5 localized in mitochondria but not in cytosol. UCP5 overexpression increased proton leak, decreased mitochondrial membrane potential (MMP), reduced ATP production, and increased overall oxygen consumption (demonstrating uncoupling activity). UCP5 overexpression did not affect other neuronal UCP expression (UCP2 and UCP4). Overexpressing UCP5 is protective against MPP+- and dopamine-induced toxicity. MPP+ and dopamine exposure for 6 h reduced MMP and increased superoxide levels. ATP levels in UCP5-overexpressing cells were preserved under MPP+ and dopamine toxicity, comparable to levels in untreated vector controls. At 24 h, UCP5 overexpression preserved MMP, ATP levels, and cell survival; attenuated superoxide generation; and maintained oxidative phosphorylation as indicated by lower lactate levels. MPP+ and dopamine exposure induced UCP5 mRNA transcription but did not decrease transcript degradation, as inhibition of transcription by actinomycin-D abolished induction by either toxin. Compared with our previous studies on UCP4, we observed functional differences between UCP4 and UCP5 in enhancing mitochondrial efficiency. These neuronal UCP homologues may work synergistically to maintain oxidative balance (through uncoupling activities) and ATP production (by modifying MMP).

In this paper, we firstly give the definition of meromorphic function element and algebroid mapping. We also construct the algebroid function family in which the arithmetic, differential operations is closed. On basis of these works, we firstly proved the Second Main Theorem concerning small algebroid functions for v-valued algebroid functions.

Mitochondrial uncoupling protein-4 (UCP4) enhances neuronal cell survival in MPP(+)-induced toxicity by suppressing oxidative stress and preserving intracellular ATP and mitochondrial membrane potential. UCP4 expression is increased by MPP(+), but its regulation is unknown. Using serial human UCP4 promoter-luciferase reporter gene constructs, we identified and characterized several cis-acting elements that can regulate UCP4 expression. Core promoter activity exists within 100 bp upstream of the transcription initiation site (TIS=+1). Both CAAT box (-33/-27) and Sp1 (-62/-49) elements are crucial and act synergistically in its transcription. We identified a NF-kappaB putative binding site at -507/-495. Mutation of this site significantly decreased UCP4 promoter activity. Activation of NF-kappaB by TNFalpha or cycloheximide increased, whereas its inhibition by 4-hydroxy-2-nonenal or transfection of pIkappaBalphaM suppressed, UCP4 promoter activity. NF-kappaB inhibition significantly suppressed the MPP(+)-induced increase in UCP4 expression. MPP(+) increased specific binding of NF-kappaB protein complexes to this site in electrophoretic mobility shift assay. Both UCP4 knockdown and NF-kappaB inhibition exacerbated MPP(+)-induced cell death. We present the first direct evidence that UCP4 is regulated by NF-kappaB, mediated via a functional NF-kappaB site in its promoter region, and that UCP4 has a significant role in NF-kappaB prosurvival signaling, mediating its protection against MPP(+) toxicity.

To identify the gene mutation type of an inherited coagulation factor XIII (FXIII) deficiency pedigree.PCR and DNA sequencing were used to identify the mutations in the 15 exons and the flank sequence of FXIII gene in the proband. The identified mutations were validated by allele specific PCR, PCR restriction fragment length polymorphism technique or DNA sequencing in the family members and 100 healthy volunteers.Arg77Cys and Argl74stop double heterozygous mutations were discovered in the proband. The pedigree analysis showed that Arg77Cys missense mutation inherited from her father, and Arg174stop from her mother. The Arg77Cys missense mutation in exon 3 was not found in her husband and the other 100 healthy volunteers.A novel Arg174stop nonsense mutation was discovered in human FXIII gene. A simple DNA assay based on PCR for detection of this mutation was developed. The congenital FXIII deficiency in the proband might be caused by the coinheritance of the Arg77Cys missense mutation in exon 3 and the Arg174stop nonsense mutation in exon 4.

The basic concepts of web log mining have been introduced in this paper, in which the steps and processes of web log mining are given, an distance education system model of web log mining is set up, through the analysis of experimental data of web log mining, we have got the different access patterns of visitors and give the different plan of proposing website as well as personalized service, which indicated that the application of this method used in distance education system is effectiveness.

A cost-effective compact instrument for high-stable and sensitive detection of methane (CH4) based on the tunable diode laser absorption spectroscopy technique was experimentally demonstrated. A distributed feedback laser modulated at 1654 nm and two InGaAs photodiodes were deployed in this instrument. The laser was driven by the self-developed temperature and current controller. Spectrum measurements show that the center wavelength of the laser is stable and linearly controlled. Meanwhile, a self-developed digital lock-in amplifier was developed for the extraction of harmonics (1f, 2f) of the gas absorption signal. Experiments of gas detection were carried out to investigate the sensor performance. Firstly, the relation between gas concentration and 1f and 2f harmonics was measured and the relation curve was plotted for calibration. Then, results of accuracy test in different concentrations show that the maximum relative detection error is less than 5.6% in the range 0%–100%. Keeping the other experimental parameters constant, gas samples of 5% concentration was detected during a period of 8 h. The maximum detection error is less than 2.8%, suggesting good detection stability. The sensor can also be applied to field measurement of other gases by adopting lasers at relative wavelength.

Background This study is a retrospective case analysis of 143 patients who suffered from severe intracranial hemorrhage and underwent a fast and simple procedure of cranial drilling followed with external ventricle drain treatment (referred as Fast-D here after) during 2003-2013 to evaluate the clinical effectiveness of the treatment. Methods Fast-D procedure was conducted on 143 patients with severe acute craniocerebral diseases. Those patients were evaluated using activities of daily living (ADL) scales at hospital discharge and after 6-month of physical therapy, and were compared to 36 patients with similar craniocerebral diseases but received the traditional Dandy's surgical treatment. Results At discharge, 11% (16 cases) was classified as ADL I (fully functional for physical and social activities); 26% (37 cases) had ADL II (fully functional for physical activities but partially impaired for social activities); 34% (49 cases) was ADL III (require assistance performing physical activities); 9% (13 cases) was ADL IV (being conscious, but completely lost ability of physical activities); 27% (10 cases) was ADL V (vegetative stage); and 13% (18 cased) was ADL VI (died) among the 143 patients. Six-month physical therapy improved ADL in 88% of the patients. Those outcomes are equal or better than the more complicated Dandy's procedure probably due to the time-saving factor. Conclusion Fast-D procedure is much faster (6.7 min vs. 53.6 min of the Dandy's procedure) and can be performed outside operating rooms (computed tomography room or bedside). This technique could serve as a tool to rapidly release intracranial pressure and reduce subsequent morbidity and mortality of severe craniocerebral diseases when resource and condition are limited and more elaborate operating room procedures are not possible.

To discover the mutations of human blood coagulation factor V (FV) gene in a Chinese family with congenital factor V deficiency, and to explore the molecular mechanism associated with the congenital factor V deficiency.PCR and DNA sequencing were used to look for the FV gene mutations in the proband. And the novel mutation were testified by PCR restriction fragment length polymorphism technique or reverse DNA sequencing. One hundred healthy volunteers were chosen as controls at random.Two novel mutations were discovered in the FV gene of proband, which were the A1763C missense mutation in exon 11 and the splicing site mutation in the 3' terminal of intron 16 (G--T). The pedigree analysis showed that the two mutations inherited from his parents respectively: the A1763C came from his father, and the G--T from his mother. The A1763C missense mutation in exon 11 was not found in each of 100 healthy volunteers.The congenital deficiency of FV in the proband might be caused by the A1763C missense mutation in exon 11 and the splicing site mutation in the 3' terminal of intron 16, which jointly caused the proband to be a double heterozygote.

To investigate the clinical manifestations, complications and treatment of medicament-like dermatitis due to trichloroethylene (TCE), so as to provide basis for studying its etiology and mechanism.Fifty patients with dermatitis due to TCE from 1997 to 2000 were analysed retrospectively.The occurrence of the dermatitis was not parallel to TCE exposure levels, without significant dose-effect relationship. This disease could be caused by both inhalation and skin exposure. The latency period of TCE dermatitis ranged from 5 to 66 days, and the average was 31.5 d (Medium). The major clinical manifestations included skin lesions, fever, superficial lymph node swelling and liver dysfunction. Infection was the major complication. Glucocorticoid was effective for treatment of this disease.The clinical manifestations due to TCE exposure were similar to dermatitis medicamentosa. The major clinical types of TCE dermatitis included exfoliative dermatitis and erythema multiforme. The dermatitis is considered to be mediated by delayed-type (IV) hypersensitivity. The key factors to treat this disease successfully included the use of glucocorticoid in time with sufficient dose and full course, professional skin care, active treatment to protect the liver and to avoid infection.

To study the dioxin level of breast milk among Chinese mothers, and to assess the dioxin intake of new-born babies from mother's milk and compare with the Tolerable Daily Intake (TDI) of dioxin.The CALUX bioassay was used to detect the dioxin concentration of the first time mother's milk among the inland samples (Shenyang region; 32 cases) and the coastal city samples (Dalian region; 47 cases).The median value of the dioxin Toxic Equivalence (TEQ) in breast milk in the Dalian region was 15.84 pg TEQs.g(-1) fat, which was significantly higher than that in the Shenyang region 7.21 pg TEQs.g(-1) fat (P0.01).The dioxin level in breast milk in Chinese is at the world's average level. The dioxin intake of the new-born babies during the period of lactation was higher than the lowest limit of the Tolerable Daily Intake (TDI) proposed by WHO. This situation should be noticed by the related authorities.

Xenoestrogens are either natural or synthetic compounds that mimic the effects of endogenous estrogen. These compounds, such as bisphenol-A (BPA), and phthalates, are commonly found in plastic wares. Exposure to these compounds poses major risk to human health because of the potential to cause endocrine disruption. There is huge demand for a wide range of chemicals to be assessed for such potential for the sake of public health. Classical in vivo assays for endocrine disruption are comprehensive but time-consuming and require sacrifice of experimental animals. Simple preliminary in vitro screening assays can reduce the time and expense involved. We previously demonstrated that catechol-O-methyltransferase (COMT) is transcriptionally regulated by estrogen via estrogen receptor (ER). Therefore, detecting corresponding changes of COMT expression in estrogen-responsive cells may be a useful method to estimate estrogenic effects of various compounds. We developed a novel cell-based ELISA to evaluate cellular response to estrogenicity by reduction of soluble-COMT expression in ER-positive MCF-7 cells exposed to estrogenic compounds. In contrast to various existing methods that only detect bioactivity, this method elucidates direct physiological effect in a living cell in response to a compound. We validated our assay using three well-characterized estrogenic plasticizers - BPA, benzyl butyl phthalate (BBP), and di-n-butyl phthalate (DBP). Cells were exposed to either these plasticizers or 17β-estradiol (E2) in estrogen-depleted medium with or without an ER-antagonist, ICI 182,780, and COMT expression assayed. Exposure to each of these plasticizers (10(-9)-10(-7)M) dose-dependently reduced COMT expression (p

Aiming at the advantages of giant magnetostrictive actuator and its application prospect in the field of cutting with invariableness cutting force, a method that keeping the actuator output a constant force was proposed. Based on analysing the influence law of working boundary conditions on magnetisation state, this paper suggests that using the positive and inverse effect models to independently determine magnetisation state in giant magnetostrictive material rod under the action of magnetic and stress, respectively, and using the method of repeatedly mutual calling magnetisation results as the initial magnetisation state of calculation again to rescind the coupling effect between positive and inverse effects. It realised the actuator outputting constant force by the combination of inverse model of magnetostrictive positive effect and elastic modulus expression. Experimental results showed that the method can effectively calculate the working current which makes actuator output constant force. All the relative errors are less than 1%.

Utilising a giant magnetostrictive material (GMM) rod as the sensitive element, a new type of magnetostrictive force sensor is studied. A Hall sensor with a stainless steel ring integrated in the sensor is used to measure the bias magnetic field intensity. In view of the hysteresis of GMM, a model for the sensor is established based on Jiles–Atherton model and magnetomechanical effect method. Moreover, the numerical solution method and simulation process of the model are expounded in detail. The simulation results show that the model can reveal the process mechanism of magnetisation and have a good ability in describing the hysteretic non-linearity. The experimental results indicate that the model can effectively describe the relationship between the induced voltage and force under a constant magnetic field and dynamic force simultaneously.

Giant magnetostrictive material (GMM) exhibits an apparent change in elastic modulus at different magnetisation and stress states. Therefore, to describe output performance of GMM accurately, it needs to determine the change law of elastic modulus for GMM. In this paper, from the viewpoint of the internal energy of GMM and combining with the experimental characteristics of GMM rod, an elastic modulus model for GMM rod under the combined action of external stress and magnetic field is derived. In this model, Langevin function is used to describe the magnetisation curve of magnetic field. Change law of elastic modulus with stress and magnetic field is revealed through a simulation analysis. Experimental results exhibit that the predicted elastic modulus is in good agreement with the experimental data. The average relative error between experimental data and calculated result is about 2.05%.

In this paper, a novel giant magnetostrictive force sensor which uses a giant magnetostrictive materials rod as the sensitive element was studied. The sensor realised static force and dynamic force measuring through an integrated linear hall sensor and a pickup coil respectively. Based on a deep analysis of the relationship between magnetic flux density measured by hall sensor and actual magnetic flux density in giant magnetostrictive materials rod, combining the non-linear constitutive equations and electromagnetic induction law, the paper expounded the principle of simultaneously measuring static and dynamic force. Based on this, the influence laws of bias magnetic field, pre-tightening force, pickup coil turns, length of giant magnetostrictive materials rod, amplitude of exciting force and other factors on sensor’s output characteristics are determined through experimental and theoretical analysis. The research results provide a technical way for further research of giant magnetostrictive force sensor.

1. Glucuronidation of clofibric acid, the pharmacologically active form of the hypolipidemic drug clofibrate was investigated in a human population, either in vitro with liver homogenates from biopsies, or after ingestion of the drug and determination of the urinary metabolite. No difference in the glucuronidation rate according to age of the patients was observed. Bilirubin but not clofibric acid glucuronidation was significantly higher in women (106% increase), when expressed per gram of tissue. 2. The excretion of clofibryl glucuronide in women who took oral contraceptives was significantly enhanced by 25%. 3. In female rats, treatment with the contraceptive agent norethindrone also stimulated by 48% the formation of clofibrylglucuronide in liver microsomes.The effect of oral contraceptive (OC) intake on the glucuronidation of clofibric acid was investigated both in vivo, by measuring the excretion of urinary clofibrylglucuronide in female Wistar rats, or in vitro, with liver biopsy homogenates from 69 health female volunteers. In both study groups norethindrone markedly enhanced glucuronidation of clofibric acid while the situation was modulated by the administration of ethinyl estradiol. Excretion of clofibric acid into urine averaged 142.1 + or - 38.4 mg in OC users compared to only 105.8 + or - 31.5 mg in non-users. When expressed per gram of tissue, bilirubin but not clofibric acid glucuronidation was significantly greater in human liver biopsies from OC users compared to non-users. In rats treated with norethindrone, the liver microsomal protein content was increased 28% over the average control value and formation of clofibylglucoride was stimulated by 48%. It is hypothesized that the stimulation of clofibylglucuronide in OC users results from the selective stimulation in the liver of the isoenzyme involved in the process of the glucuronidation of clofibric acid.

By introducing manganese to (Mg,Zn,Ni) divanadates, a series of thortveitite-type phases, Mn(MgxZnyNiz)V2O7 with x+y+z= 1, has been synthesized. The limits of x, y, and z can be represented by four phases: Mn(Mg0.2Zn0.8)V2O7, Mn(Mg0.5Zn0.5)V2O7, Mn(Mg0.1Zn0.8Ni0.1)V2O7, and Mn(Mg0.4Zn0.5Ni0.1)V2O7. Their cell dimensions are, respectively, a= 0.6734, 0.6737, 0.6749, and 0.6749 nm, b= 0.8806, 0.8819, 0.8816, and 0.8787 nm, c= 0.4748, 0.4750, 0.4752, and 0.4753 nm, and β= 102.16°, 102.15°, 102.23°, and 102.41°.

An ion-pair high-performance liquid chromatographic technique has been developed to reduce the elution times of both glucuronic acid conjugates and their free aglycones. The chromatographic system combines the use of a reversed-phase column (LiChrospher CH-18; 5 μm) and a mobile phase of methanol (70–80%)–0.01 M phosphate buffer (pH 6.0) containing 2.5 mM cethexonium bromide as counter-ion at a flow-rate of 1 ml min-1. The hydrophobicity of this quaternary ammonium ion-pairing reagent and the high content of the organic modifier in the mobile phase provide close and short elution times for a wide structural variety of compounds (i.e. alcohols, phenols, steroids, carboxylic acids) and their conjugates with glucuronic acid (capacity factors lower than 7.5), without compromising the selectivity with respect to endogenous compounds of the microsomal incubation medium and urine. Advantages of cethexonium bromide over conventional tetrabutylammonium salts are clearly demonstrated, and the described system was applied to the simultaneous quantitation of clofibric acid and its acylglucuronide in human urine and validated for a pharmacogenetics purpose.

This review gives a brief insight into the role of mitochondrial dysfunction and oxidative stress in the converging pathogenic processes involved in Parkinson's disease (PD). Mitochondria provide cellular energy in the form of ATP via oxidative phosphorylation, but as an integral part of this process, superoxides and other reactive oxygen species are also produced. Excessive free radical production contributes to oxidative stress. Cells have evolved to handle such stress via various endogenous anti-oxidant proteins. One such family of proteins is the mitochondrial uncoupling proteins (UCPs), which are anion carriers located in the mitochondrial inner membrane. There are five known homologues (UCP1 to 5), of which UCP4 and 5 are predominantly expressed in neural cells. In a series of previous publications, we have shown how these neuronal UCPs respond to 1-methyl-4-phenylpyridinium (MPP+; toxic metabolite of MPTP) and dopamine-induced toxicity to alleviate neuronal cell death by preserving ATP levels and mitochondrial membrane potential, and reducing oxidative stress. We also showed how their expression can be influenced by nuclear factor kappa-B (NF-kappaB) signaling pathway specifically in UCP4. Furthermore, we previously reported an interesting link between PD and metabolic processes through the protective effects of leptin (hormone produced by adipocytes) acting via UCP2 against MPP+-induced toxicity. There is increasing evidence that these endogenous neuronal UCPs can play a vital role to protect neurons against various pathogenic stresses including those associated with PD. Their expression, which can be induced, may well be a potential therapeutic target for various drugs to alleviate the harmful effects of pathogenic processes in PD and hence modify the progression of this disease., published_or_final_version