A Novel Spatial Position Prediction Navigation System Makes Surgery More Accurate.

During intravascular interventional surgery, the 3D surgical navigation system can provide doctors with 3D spatial information of the vascular lumen, reducing the impact of missing dimension caused by digital subtraction angiography (DSA) guidance and further improving the success rate of surgeries. Nevertheless, this task often comes with the challenge of complex registration problems due to vessel deformation caused by respiratory motion and high requirements for the surgical environment because of the dependence on external electromagnetic sensors. This article proposes a novel 3D spatial predictive positioning navigation (SPPN) technique to predict the real-time tip position of surgical instruments. In the first stage, we propose a trajectory prediction algorithm integrated with instrumental morphological constraints to generate the initial trajectory. Then, a novel hybrid physical model is designed to estimate the trajectory's energy and mechanics. In the second stage, a point cloud clustering algorithm applies multi-information fusion to generate the maximum probability endpoint cloud. Then, an energy-weighted probability density function is introduced using statistical analysis to achieve the prediction of the 3D spatial location of instrument endpoints. Extensive experiments are conducted on 3D-printed human artery and vein models based on a high-precision electromagnetic tracking system. Experimental results demonstrate the outstanding performance of our method, reaching 98.2% of the achievement ratio and less than 3 mm of the average positioning accuracy. This work is the first 3D surgical navigation algorithm that entirely relies on vascular interventional robot sensors, effectively improving the accuracy of interventional surgery and making it more accessible for primary surgeons.

Association between quantitative spectral CT parameters, Ki-67 expression, and invasiveness in lung adenocarcinoma manifesting as ground-glass nodules.

BACKGROUND: Few studies about lung ground-glass nodules (GGNs) have been done using non-enhancement spectral computed tomography (CT) imaging. PURPOSE: To examine the association between spectral CT parameters, Ki-67 expression, and invasiveness in lung adenocarcinoma manifesting as GGNs. MATERIAL AND METHODS: Spectral CT parameters were analyzed in 106 patients with lung GGNs. The Ki-67 labeling index (Ki-67 LI) was measured, and patients were divided into low expression and high expression groups according to the number of positive-stained cells (low expression ≤10%; high expression >10%). Spectral CT parameters were compared between low and high expression groups. The correlation between spectral CT parameters and Ki-67 LI was estimated by Spearman correlation analysis. Cases were divided into a preinvasive and minimally invasive adenocarcinoma (MIA) group (atypical adenomatous hyperplasia, adenocarcinoma in situ, and MIA) and invasive adenocarcinoma (IA) group. Spectral CT parameters were compared between the two groups. The diagnostic performance was evaluated using receiver operating characteristic analysis. RESULTS: There were significant differences in water concentration of lesions (WCL) and monochromatic CT values between the low and high expression groups. CT 40 keV had the highest correlation coefficient with Ki-67 LI. WCL and monochromatic CT values were significantly higher in the IA group than in the pre/MIA group. The value of area under the curve of CT 40 keV was 0.946 (95% confidence interval=0.905-0.988) for differentiating the two groups; the cutoff was -280.66 Hu. CONCLUSION: Spectral CT is an effective non-invasive method for the prediction of proliferation and invasiveness in lung adenocarcinoma manifesting as GGNs.

Ostreibacterium oceani gen. nov., sp. nov., isolated from oyster, and description of Ostreibacteriaceae fam. nov.

A novel Gram-stain-negative, short rod-shaped, facultatively anaerobic, non-motile, non-gliding, oxidase-positive and catalase-negative bacterium, designated ML27T, was isolated from oyster homogenate in Rushan, Weihai, PR China. Growth occurred at 20-33 °C (optimum, 30 °C), at pH 7.0-9.0 (optimum, pH 7.5-8.0) and in the presence of 1-6 % (w/v) NaCl (optimum, 3 %). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain ML27T was 90.7 % similar to Suttonella ornithocola DSM 18249T, 89.2 % to Suttonella indologenes JCM 1478T and 88.2 % to Cardiobacterium hominis DSM 8339T; similarities to other species were less than 90 %. The average amino acid identity between strain ML27T, S. indologenes JCM 1478T, S. ornithocola DSM 18249T, C. hominis DSM 8339T and Dichelobacter nodosus ATCC 25549T were 46.23, 45.86, 45.54 and 45.84 %, respectively. Phylogenomic tree and phylogenetic analyses based on 16S rRNA gene sequences showed that the isolate formed a novel family-level clade in the order Cardiobacteriales. The sole respiratory quinone was ubiquinone-7 (Q-7). The dominant cellular fatty acids were summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c; 46.3 %), C16 : 0 (17.8 %) and summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c; 13.5 %). The DNA G+C content of strain ML27T was 45.6 mol%. Polar lipids included phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and one unidentified lipid. Comparative analyses of 16S rRNA gene sequences, genomic distinctiveness and characterization indicated that strain ML27T represents a novel species of a new genus within a novel family of the order Cardiobacteriales, for which the name Ostreibacterium oceani gen. nov., sp. nov. is proposed. The type strain of Ostreibacterium oceani is ML27T (=MCCC 1H00372T=KCTC 72155T). In addition, a novel family, Ostreibacteriaceae fam. nov., is proposed to accommodate the genus Ostreibacterium.

Moheibacter lacus sp. nov., Isolated from Freshwater Lake Sediment.

A Gram-stain-negative, yellow-pigmented, rod-shaped, strictly aerobic, non-motile bacterium, designated BDHS18T, was isolated from the sediment of the Hasuhai Lake, China. Phylogenetic analysis based on 16S rRNA gene sequences revealed that this strain belongs to the genus Moheibacter in the family Flavobacteriaceae and its closest relative was Moheibacter sediminis JCM 19634T (96.0%), followed by Moheibacter stercoris DSM 29388T (95.3%). Cells of strain BDHS18T were catalase-positive and oxidase-negative. Strain BDHS18T was found to grow optimally at 28-33 â„ƒ, pH 7.5-8.0, and in the presence of approximately 1.0% (w/v) NaCl. Major cellular fatty acids were iso-C15:0, iso-C17:0 3-OH, Summed feature 4 and Summed feature 9. The predominant respiratory quinone was MK-6. The predominant polar lipids in strain BDHS18T were phosphatidylethanolamine, phosphatidylglycerol, one unidentified aminolipid and one unidentified lipid. The DNA G + C content was 36.9 mol%. According to the phylogenetic analysis, physiological and phenotypic characteristics, strain BDHS18T represents a novel species of the genus Moheibacter, for which the name Moheibacter lacus sp. nov. is proposed. The type strain is BDHS18T (= KCTC 72160T = MCCC 1H00369T).

Sulfitobacter algicola sp. nov., isolated from green algae.

A novel Gram-stain-negative, aerobic, non-flagellated, non-motile, oval-rod-shaped and light pink to light tawny-pigmented bacterial strain (designated 1151T) were isolated from marine green algae obtained from the coastal seawater of Weihai, China. Strain 1151T was found to grow at 15-37 °C (optimum, 33 °C), pH 7.0-9.5 (optimum, 7.5-8.5) and in the presence of 1-6% (w/v) NaCl (optimum, 3%). Cells were oxidase-positive and catalase-positive. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain 1151T was a member of the genus Sulfitobacter and exhibited the hightest sequence similarity to Sulfitobacter indolifex DSM 14862T (96.6%), followed by the sequence similarity to Sulfitobacter aestuarii hydD52T (96.5%) and Sulfitobacter profundi SAORIC-263T (96.5%). The average nucleotide identity and digital DDH values between strain 1151T and Sulfitobacter indolifex DSM 14862T were 69.9% and 20.9%, respectively. The average amino acid identity between strain 1151T and Sulfitobacter pontiacus DSM 10014T (type strain of the type species) was 62.3%. Q-10 was detected as the sole respiratory quinone. The dominant cellular fatty acids were sum feature 8 (C18: 1ω7c; 44.1%), C20: 1ω7c (29.7%) and C18: 0 (11.7%). The DNA G + C content of strain 1151T was 51.8 mol%. The polar lipids included phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), and three unidentified lipids (L1, L2 and L3). Based on the phylogenetic and phenotypic characteristics, strain 1151T is considered to represent a novel species of the genus Sulfitobacter, for which the name Sulfitobacter algicola sp. nov. is proposed. The type strain is 1151T (= KCTC 72513T = MCCC 1H00384T).

Cytotoxic benzopyranone and xanthone derivatives from a coral symbiotic fungus Cladosporium halotolerans GXIMD 02502.

Coral-derived microorganisms have been historically proven to be prolific sources of bioactive secondary metabolites. Twelve benzopyranone and/or xanthone derivatives, including a new benzopyranone with an uncommon carboxyl group at C-8, coniochaetone K (1), were obtained from the Beibu Gulf-derived coral symbiotic fungus Cladosporium halotolerans GXIMD 02502. Their structures were determined by extensive spectroscopic data interpretation and comparison with literature values. The absolute configuration of 1 was accomplished by comparison of specific optical rotation as well as quantum chemical ECD calculations. The in vitro cytotoxicity of compounds 1-12 against two human prostatic cancer cell lines, C4-2B and 22RV1, were evaluated. And compounds 1, 3, 6-8, and 10-11 demonstrated significant cytotoxicity with inhibitions ranging from 55.8% to 82.1% at the concentration of 10 µM.

Advances in Doped ZnO Nanostructures for Gas Sensor.

Gas sensors based on metal oxides semiconductor (MOS) have attracted extensive attention from both academic and industry. ZnO, as a typical MOS, exhibits potential applications in toxic gas detection, owning to its wide band gap, n-type transport characteristic and excellent electrical performance. Meanwhile, doping is an effective way to improve the sensing performance of ZnO materials. In this review, the effects of different types of doping on morphology, crystal structure, band gap and depletion layer of ZnO materials are comprehensively discussed. Theoretical analysis on the strategies for enhancing the sensing properties of ZnO is also provided. This review puts forward the reasonable insight for designing efficient n-type ZnO-based semiconductor oxide sensing materials.

Ethanol Electrooxidation on Rhodium-Lead Catalysts in Alkaline Media: High Mass Activity, Long-Term Durability, and Considerable CO2 Selectivity.

Rhodium (Rh)-based catalysts may solve the long-standing inefficient oxidation of ethanol for direct ethanol fuel cells (DEFCs); however, the performance of ethanol oxidation reaction (EOR) on existing Rh-based catalysts are far limited. Herein, the Rh-Pb catalysts are synthesized by building Pb and Pb oxide around Rh nanodomain, which shows highly efficient splitting CC bond and facile further oxidation of as-generated C1 intermediates (COad and CHx fragments). It exhibits an ever-highest EOR peak mass activity of ≈2636 mA mg-1 Rh among Rh-based catalysts in alkaline media. Meanwhile, its anodic current remains ≈50% even after a 4 h durability test at 0.53 V versus RHE. As for the C1-pathway selectivity, in situ infrared adsorption spectral (IRAS) results demonstrate that it could significantly improve the production of CO2 . More directly, the apparent faraday efficiency of EOR C1 pathway is estimated to be as high as 20% (at 0.53 V versus RHE). This Rh-Pb catalyst could hold great promise for developing the commercial DEFCs.

Ultrathin agaric-like ZnO with Pd dopant for aniline sensor and DFT investigation.

Aniline detection is of great importance in many industries, but most of the aniline sensors suffers from tedious and time consuming process. Herein, we present an efficient aniline sensor based on Pd decorated ZnO nanomaterials. Ultrathin ZnO nanosheets were synthesized by a facile one-step hydrothermal method. The nanosheets were corrugated into a unique agaric morphology, endorsing the nanomaterials with high surface area that is ideal for gas sensing applications. The obtained ZnO nanosheets were then uniformly decorated with uniform Pd nanoparticles (Pd NPs) around 5 nm in diameter. Gas sensing experiment on the ZnO decorate with different amount of Pd nanoparticles were systematically evaluated. The sample decorated with 0.3 % Pd NPs (Pd-ZnO-0.3) exhibited the highest sensitivity to aniline, which is about two orders higher than that of the pure ZnO nanosheet. The gas sensor based on Pd-ZnO-0.3 has a detection limit to aniline down to 0.5 ppm, with very short response and recovery times of 29 s and 23 s, respectively to 100 ppm aniline. First-principles DFT study was employed to provide the sensing mechanism. The improved sensing performance could be attributed to the increasing adsorbed oxygen and tunable band alignment for Pd-ZnO materials. This work provides new insights to the design strategy of Pd-decorated ZnO nanomaterials for high performance gas sensors.

Effects of pesticide residues on bacterial community diversity and structure in typical greenhouse soils with increasing cultivation years in Northern China.

The understanding of soil microbiome is important for sustainable cultivation, especially under greenhouse conditions. Here, we investigated the changes in soil pesticide residues and microbial diversity and community structure at different cultivation years under a greenhouse system. The 9-to-14 years sites were found to have the least diversity/rich microbial population as compared to sites under 8 years and over 16 years, as analyzed with alpha diversity index. In total, 42 bacterial phyla were identified across soils with different pesticide residues and cultivation ages. Proteobacteria, Acidobacteria, and Bacteroidetes represented the dominant phyla, that accounted for 34.2-43.4%, 9.7-19.3% and 9.2-16.5% of the total population, respectively. Our data prove that certain pesticides contribute to variation in soil microbial community and that soil bacteria respond differently to cultivation years under greenhouse conditions. Thus, this study provides an insight into microbial community structure changes by pesticides under greenhouse systems and natural biodegradation may have an important part in pesticides soil decontamination.

[Case-control study on a new Kirschner wire tension band with hole in the treatment of adult olecranon fractures in adults].

OBJECTIVE: To compare the efficacy of Kirschner wire tension band with hole and common Kirschner wire tension band in the treatment of olecranon fractures in adults, so as to guide the selection of clinical surgical procedures. METHODS: From July 2011 to October 2015, a total of 49 patients with olecranon fractures underwent open reduction and fixation with Kirschner wire tension band, which were retrospectively analyzed. Of the 49 patients, 21 patients(group A) were treated with Kirschner wire tension band with hole, including 12 males and 9 females, with an average age of(37.6 ±8.2) years old;28 patients(group B) were treated with common Kirschner wire, including 18 males and 10 females, with an average age of(38.9±7.3) years old. There were no statistically significant differences between the two groups in general data. The differences of operative duration, frequency of radiation, fracture healing time, complications and postoperative elbow function scores between the two groups were observed and analyzed by parallel statistical analysis. RESULTS: In group A, the operative duration was(60.4±10.7) min, the average number of radiation times was (12.5±2.9); in group B, the operative duration was (62.3±11.8) min, and the average radiation times was(13.7±3.8); there was no significant difference in operative time and radiation times between the two groups (P >0.05). In group A, the fracture healing time was (13.2±2.6) weeks without K-wire migration, skin irritation and other complications; and fracture healing time in group B was(14.6±1.8) weeks with complications(K-wire migration in 6 cases, skin irritation in 7 cases, internal fixation failure in 2 cases);the fracture healing time of group A was shorter than that in group B. Evaluation of elbow joint function in two groups of patients after operation showed that in group A, pain score was 41.0±3.5, movement function score was 18.0±2.1, stability score was 9.0±0.8, daily activities score was 18.0±4.3, the total average score was 87.0±7.8; and in group B, the pain score was 39.0±5.6, movement function score was 17.0±3.2, the stability score was 8.0±2.4, daily activities score was 16.0±5.2, the total average score was 83.0±10.7. There were no statistically significant in the scores between the two groups. CONCLUSIONS: Compared with ordinary Kirschner wire, the treatment of olecranon fracture with Kirschner tension band with hole can shorten the time of fracture healing, significantly reduce the occurrence of complications, and do not affect the recovery of postoperative function, which is suitable for clinical use.

Percutaneous Endovenous Intervention Plus Anticoagulation versus Anticoagulation Alone for Treating Patients with Proximal Deep Vein Thrombosis: A Meta-analysis and Systematic Review.

BACKGROUND: Combination treatment with percutaneous endovenous intervention (PEVI) and anticoagulation has been proposed for treating lower-extremity proximal deep vein thrombosis (DVT). We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of PEVI plus anticoagulation versus anticoagulation alone in patients with lower-extremity proximal DVT. METHODS: We systematically searched PubMed, Embase, and the Cochrane Library from inception to May 2016. All RCTs comparing clinical outcomes between additional PEVI and anticoagulation alone were included. The main end points were postthrombotic syndrome (PTS) and major bleeding complications. Secondary outcomes included the iliofemoral patency rate, venous obstruction, and recurrent DVT. We assessed pooled data using a random-effects model. RESULTS: Four RCTs were included. PEVI plus standard anticoagulation compared with anticoagulation alone was associated with a lower rate of PTS (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.18-0.63), significantly higher iliofemoral patency rate at 6 months and 12 months (OR 8.49, 95% CI 1.32-54.60), a lower rate of venous obstruction (OR 0.42, 95% CI 0.20-0.924), and a lower rate of recurrent DVT (OR 0.42, 95% CI 0.20-0.92). However, more major bleeding episodes occurred in the group with catheter-directed thrombolysis (Peto OR 5.86, 95% CI 1.76-19.48). CONCLUSIONS: PEVI plus anticoagulation reduced the occurrence of PTS, recurrent DVT, and venous obstruction. Another advantage is an increased patency rate at 6 and 12 months. The disadvantage is an increased occurrence of major bleeding events.

Discovery of novel inhibitors of RNA silencing suppressor P19 based on virtual screening.

To control plant viruses, viral RNA silencing suppressors are important drug targets due to their key roles in interfering antiviral RNA silencing. Here we have presented a strategy, combining virtual and experimental screening, to discover the inhibitors of viral suppressor. By docking 157 026 compounds from a natural product library into P19 model, eighteen candidate compounds were selected. Candidates VS2, VS12, VS14 and VS15 displayed strong binding ability to P19 in the surface plasmon resonance imaging assay with K D values of 136.2, 111.6, 81.2 and 124.5 nM, respectively. Then the inhibition activities of these inhibitors on the association between P19 and siRNA were also affirmed by electrophoretic mobility shift assay. Moreover, the antiviral effects on plants showed that compounds VS14 and VS15 both exhibited antiviral activities against Tomato bushy stunt virus (TBSV) in vivo with inhibition rates of 32.35% and 16.61% in 11 dpi, respectively. This strategy would be a powerful tool for the discovery of novel antiviral agents and provide new insights into the control of plant viruses.

Adipocytes promote nicotine-induced injury of endothelial cells via the NF-κB pathway.

Cigarette smoking is one of the most important risk factors of atherosclerosis, which can induce endothelial injury. Meanwhile, adipocytes are the main cell type of perivascular adipose tissue (PVAT), the largest endocrine and paracrine organ and direct anatomical connection to adventitia, which may play a key role in the injury of endothelial cells. We used nicotine to induce dysfunctional HUVECs and adipocytes. In addition, we used a novel model to co-culture HUVECs and adipocytes in vitro by the transwell co-culture system to determine the effect of adipocytes on endothelial injury. Cell apoptosis was detected by Annexin V-FITC. Genes and proteins involved in the nuclear factor kappa B (NF-κB) signaling pathway were detected by qRT-PCR and western blot analysis, respectively. We also investigated the nuclear translocation of NF-κB p65 using immunofluorescence staining. Our results showed that nicotine dose-dependently induces the apoptosis of HUVECs and adipocytes and is associated with increased IKKß and NF-κB p65 expression and with IkBα degradation. Meanwhile through the co-culture system, adipocytes promoted the expression of IKKß and NF-κB p65, as well as the translocation of NF-κB p65, and they accelerated the degradation of IkBα, resulting in increased apoptosis of HUVECs compared with that of the single cultured system. In conclusion, adipocytes could promote endothelial injury via the NF-κB pathway. Moreover, the NF-κB pathway plays pivotal roles in nicotine-induced vascular injury.

Role of perivascular adipose tissue in nicotine­induced endothelial cell inflammatory responses.

Smoking is considered to be one of the primary causes of atherosclerosis and vascular injury. Previous studies have shown that nicotine in tobacco can lead to vascular inflammation and endothelial dysfunction. Perivascular adipose tissue (PVAT) is known to secrete various types of adipokines to maintain vascular homeostasis. The present study investigated whether nicotine­induced PVAT malfunction can accelerate endothelial inflammation and eventually lead to endothelial dysfunction. The levels of inflammatory adipokines, including nuclear factor (NF)­κB, interleukin (IL)­1ß, IL­6 and tumor necrosis factor (TNF)­α, the ICAM­1 and VCAM­1 adhesion molecules and secretion of adiponectin were assessed in mature adipocytes and endothelial cells cultured alone or in co­culture under nicotine stimulation. It was found that nicotine reduced the secretion of adiponectin and stimulated secretion of the NF­κB, IL­1ß, IL­6 and TNF­α inflammatory adipokines in mature adipocytes. Although nicotine stimulated endothelial cells to secrete IL­1ß and IL­6, no significant increase in the secretion of TNF­α was observed. The co­culture of mature adipocytes with endothelial cells markedly augmented the expression of the NF­κB, IL­1ß, IL­6 and TNF­α inflammatory adipokines and the ICAM­1 and VCAM­1 adhesion molecules, and significantly lowered the levels of adiponectin. These findings suggested that nicotine induced mature adipocyte dysfunction, which caused the abnormal secretion of adiponectin and inflammatory adipokines, and exacerbated endothelial inflammation. These findings also suggested a mechanism whereby nicotine induced the secretion of adiponectin and inflammatory cytokines by adipocytes. The results of the present study elucidated a novel pathway induced by cigarette smoke, which contributed to atherosclerosis and vascular injury.

[Logistic Regression Analysis of Depression in Arteriosclerosis Obliterans Patients and Its Risk Factors].

OBJECTIVE: To investigate the depression in arteriosclerosis obliterans (ASO) patients and its risk factors. METHODS: The self-rating depression scale (SDS) was applied in 228 ASO patients hospitalized in the vascular surgery department of Peking Union Medical College Hospital from March 2010 to October 2011. The risk factors of depression were analyzed by using univariate and multivariate Logistic regression analysis. RESULTS: Of these 228 ASO patients, 133 (58.3%) were found to be depressive. Univariate and multivariate analysis showed that female (OR=0.15,95% CI:0.05-0.45), hypertension (OR=4.63,95% CI:1.90-11.29), coronary heart disease (OR=3.62,95%CI:1.43-9.18), as well as Fontaine 2a (OR=20.76,95% CI:3.21-134.28), 2b (OR=26.34,95% CI:4.20-164.97), 3(OR=192.28,95% CI:25.97-1423.51), and 4(OR=291.41,95% CI:28.67-2962.21) were the risk factors of depression in ASO patients. CONCLUSIONS: ASO patients can easily develop depression. Female, hypertension, coronary heart disease, and Fontaine 2a, 2b,3,and 4 are the risk factors of depression in ASO patients.

Femoral fractures in infants: a comparison of Bryant traction and modified Pavlik harness.

Bryant traction is a commonly used method for femoral shaft fractures in children, but many disadvantages have been reported. Pavlik harness with exact clinical effect and fewer complications has gained increasing popularity in resent years. The objective of this study was to evaluate and compare modified Pavlik harness with Bryant traction for infant with a femoral shaft fracture. A retrospective study was performed of 38 infants treated with either modified Pavlik Harness or Bryant traction. All fractures were closed, isolated, and diaphyseal. We analyzed operative and radiographic data, complications, hospital charges, and functional outcome. Twenty-one patients, with a mean age of 5.9 months, were treated with modified Pavlik harnesses. Seventeen infants, with a mean age of 6.3 months, were treated with Bryant tractions. All fractures united within 3-5 weeks. The two cohorts were similar with respect to age, weight, and fracture union time. Four of the seventeen children treated with Bryant tractions had a skin complication that needed second intervention. No similar complications occurred in the modified Pavlik group (p = 0.03). There was a significant difference in hospital stay (modified Pavlik harness 1.4 days versus Bryant traction 17.8 days) and hospital charge (modified Pavlik harness 3209 Yuan versus Bryant traction 3759 Yuan) (p < 0.001). At one year visit, no difference existed between the two groups for standard clinical/functional criteria. There were no malunion, nonunion, or rotational deformities. Nor were there any significant limb length discrepancies, residual angular deformities.

Paraoxonase 1 polymorphisms L55M and Q192R were not risk factors for Parkinson's disease: a HuGE review and meta-analysis.

PURPOSE: The Paraoxonase 1 (PON1) has been studied as a potential candidate gene for Parkinson's disease risk, but direct evidence from genetic association studies remains inconclusive. We performed a meta-analysis pooling data from all relevant studies in order to determine the effects of two PON 1 polymorphisms (L55M and Q192R) on Parkinson's disease. METHODS: We applied a random effects to combine odds ratio (OR) and 95% confidence intervals. Q statistic was used to evaluate the homogeneity, and Egger's test and Funnel plot were used to assess publication bias. In secondary analyses, we examined dominant and recessive models as well. RESULTS: Concerning the PON1 L55M polymorphism, we identified 9 eligible studies (a total of 2582 cases and 3997 controls). The random effects pooled OR was OR=1.29, (0.90, 1.84). Concerning the Q192R polymorphism, we identified 7 eligible studies (a total of 2582 cases and 3997 controls). The random effects pooled OR was OR=1.08(0.81, 1.43). Analysis with dominant and recessive genetic models yielded the same inferences as genotype-based comparisons for both of the two polymorphisms. CONCLUSION: The results of this meta-analysis suggested that both PON1 L55M and Q192R were not responsible for PD.

Lysine 92 amino acid residue of USP46, a gene associated with 'behavioral despair' in mice, influences the deubiquitinating enzyme activity.

Deubiquitinating enzymes (DUBs) regulate diverse cellular functions by their activity of cleaving ubiquitin from specific protein substrates. Ubiquitin-Specific Protease 46 (USP46) has recently been identified as a quantitative trait gene responsible for immobility in the tail suspension test and forced swimming test in mice. Mice with a lysine codon (Lys 92) deletion in USP46 exhibited loss of 'behavioral despair' under inescapable stresses in addition to abnormalities in circadian behavioral rhythms and the GABAergic system. However, whether this deletion affects enzyme activity is unknown. Here we show that USP46 has deubiquitinating enzyme activity detected by USP cleavage assay using GST-Ub52 as a model substrate. Interestingly, compared to wild type, the Lys 92 deletion mutant resulted in a decreased deubiquitinating enzyme activity of 27.04%. We also determined the relative expression levels of Usp46 in rat tissues using real-time RT-PCR. Usp46 mRNA was expressed in various tissues examined including brain, with the highest expression in spleen. In addition, like rat USP46, both human and mouse USP46 are active toward to the model substrate, indicating the USP cleavage assay is a simple method for testing the deubiquitinating enzyme activity of USP46. These results suggest that the Lys 92 deletion of USP46 could influence enzyme activity and thereby provide a molecular clue how the enzyme regulating the pathogenesis of mental illnesses.