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Objective: To explore risk factors of electrical status epilepticus during sleep in children with benign childhood epilepsy with centro-temporal spikes (BECT). Methods: This is a clinical comparative study. The subjects of study were 67 children with BECT from the Outpatient Department of Pediatric Neurology in Xingtai People's Hospital from January 2019 to January 2022. According to the occurrence of ESES, the enrolled children were divided into control group which included BECT children without ESES and the observation group which included BECT children with ESES. Compared differences of the two groups in the age of first seizure, the frequency of seizures before treatment, the classification of treatment drugs, cranial MRI, and discharge side of electroencephalogram (EEG). Results: There was no statistical difference between the two groups in the frequency of seizures before treatment, the classification of treatment drugs, cranial MRI, and the distribution of EEG discharges in the left and right cerebral areas(P>0.05). Statistical differences were observed in the age of the first seizure, whether the seizures occurred after treatment, and EEG discharges in unilateral/bilateral cerebral areas (P<0.05). Furthermore, the collinearity test and Logistic regression analysis showed that the age of the first seizure, the frequency of seizures before treatment, and whether the seizures occurred after treatment were independent risk factors for the occurrence of ESES in BECT (P<0.05). Conclusion: Clinically, the occurrence of ESES in children with BECT may be related to the younger age of the first seizure, higher frequency of seizures before treatment, and the occurrence of seizures after treatment. [ABSTRACT FROM AUTHOR]

Itaconate has emerged as a critical immunoregulatory metabolite. Here, we examined the therapeutic potential of itaconate in atherosclerosis. We found that both itaconate and the enzyme that synthesizes it, aconitate decarboxylase 1 (Acod1, also known as immune-responsive gene 1 [IRG1]), are upregulated during atherogenesis in mice. Deletion of Acod1 in myeloid cells exacerbated inflammation and atherosclerosis in vivo and resulted in an elevated frequency of a specific subset of M1-polarized proinflammatory macrophages in the atherosclerotic aorta. Importantly, Acod1 levels were inversely correlated with clinical occlusion in atherosclerotic human aorta specimens. Treating mice with the itaconate derivative 4-octyl itaconate attenuated inflammation and atherosclerosis induced by high cholesterol. Mechanistically, we found that the antioxidant transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), was required for itaconate to suppress macrophage activation induced by oxidized lipids in vitro and to decrease atherosclerotic lesion areas in vivo. Overall, our work shows that itaconate suppresses atherogenesis by inducing Nrf2-dependent inhibition of proinflammatory responses in macrophages. Activation of the itaconate pathway may represent an important approach to treat atherosclerosis. [ABSTRACT FROM AUTHOR]

The mechanism of Late Cretaceous crustal thickening and exhumation of the southern Lhasa terrane is critical for understanding the tectonic evolution of the Tibetan Plateau. High-pressure metamorphic rocks from the lower crust are good candidates for addressing this issue. In this study, we focus on Late Cretaceous, high-pressure, garnet-bearing amphibolites from the Nyingchi Complex of the Eastern Himalayan Syntaxis and present an integrated study of geochronology, petrography, mineral chemistry, and thermodynamic modeling. Petrographic data determine three metamorphic stages (M1-M3). The M1 stage is characterized by a peak mineral assemblage of garnet + hornblende + albite + rutile + muscovite + quartz, which is followed by a post-peak (M2) assemblage of garnet + hornblende + plagioclase + epidote + biotite + rutile + quartz. The late retrograde stage (M3) is defined by hornblende + plagioclase symplectites surrounding garnet porphyroblasts. Mineral chemistry, with thermodynamic modeling, constrains the P-T conditions of the M1- M3 stages to 14-19 kbar/660-720 °C, 8-10 kbar/650-660 °C, and <7 kbar/<600 °C, respectively. Metamorphic zircons yield a concordant age at 90 Ma, which indicates the formation of garnet-bearing amphibolites. These results indicate a P-T-t path involving near-isothermal decompression for garnetbearing amphibolites, which suggests that the Nyingchi Complex underwent peak-pressure metamorphism (M1) at 90 Ma, followed by rapid exhumation to the depth of 32-26 km along the subduction channel. Moreover, the garnet-bearing amphibolites are considered to be the product of high-pressure metamorphism of mafic crust at the base of the Gangdese belt. Hence, the crust of the Gangdese belt experienced significant crustal thickening of up to 60 km at 90 Ma. [ABSTRACT FROM AUTHOR]

Pb can damage the physiological function of human organs by entering the human body via food-chain enrichment. Revealing the mechanisms of maize tolerance to Pb is critical for preventing this. In this study, a Pb-tolerant maize inbred line, 178, was used to analyse transcription factors (TFs) expressed under Pb stress based on RNA sequencing data. A total of 464 genes expressed in control check (CK) or Pb treatment samples were annotated as TFs. Among them, 262 differentially expressed transcription factors (DETs) were identified that responded to Pb treatment. Furthermore, the DETs were classified into 4 classes according to their expression patterns, and 17, 12 and 2 DETs were significantly annotated to plant hormone signal transduction, basal transcription factors and base excision repair, respectively. Seventeen DETs were found to participate in the plant hormone signal transduction pathway, where basic leucine zippers (bZIPs) were the most significantly enriched TFs, with 12 members involved. We further obtained 5 Arabidopsis transfer DNA (T-DNA) mutants for 6 of the maize bZIPs, among which the mutants atbzip20 and atbzip47, representing ZmbZIP54 and ZmbZIP107, showed obviously inhibited growth of roots and above-ground parts, compared with wild type. Five highly Pb-tolerant and 5 highly Pb-sensitive in maize lines were subjected to DNA polymorphism and expression level analysis of ZmbZIP54 and ZmbZIP107. The results suggested that differences in bZIPs expression partially accounted for the differences in Pb-tolerance among the maize lines. Our results contribute to the understanding of the molecular regulation mechanisms of TFs in maize under Pb stress. [ABSTRACT FROM AUTHOR]

In this study, we investigated the rejection of the synthetic patch and human tissues in the host. We observed the growth of adipose-derived stem cells (ADSCs) cultured with polypropylene mesh in vitro. The results of flow cytometry showed that the expression of CD44, CD73, CD90, CD45, CD14 and CD34 was 98.54, 95.32, 98.49, 1.21, 3.01 and 2.14%, respectively. ADSCs were isolated from rabbit subcutaneous adipose tissue after collagenase digestion, filtration and centrifugation. The ADSCs of passage 3 were seeded onto the polypropylene mesh scaffolds. New Zealand White female breeder rabbits were implanted with polypropylene mesh, ADSC-fixed polypropylene mesh in the abdomen. After 4 weeks, adhesion was performed and the erosion of the mesh was evaluated. It was found that polypropylene mesh, ADSC-fixed polypropylene mesh all had different degrees of corrosion, and adhesion, but polypropylene mesh was more corroded. ADSC-fixed polypropylene mesh induced a milder chronic inflammation response compared with polypropylene, had significantly lower scores for inflammation (t=11.083), and had significantly higher scores for neovascularization (t=14.362) and fibroblastic proliferation (t=15.979). The relative amount of VEGF mRNA was significantly lower for ADSCfixed polypropylene compared with the other polypropylene meshes (t=94.6). In conclusion, polypropylene mesh scaffold with ADSCs exhibit excellent cellular compatibility and are promising in clinical practice. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) have been reported to participate in the formation of supportive tumor stroma. The abilities of proliferation and invasion of human epithelial ovarian cancer (EOC) cells were significantly enhanced when indirectly cocultured with human omental adipose-derived MSCs (O-ADSCs) in vitro. However, the underlying mechanisms remain poorly understood. In this study, EOC cells were cultured with conditioned medium (CM) from O-ADSCs (O-ADSC), and the effect of O-ADSC CM on the proteomic profile of EOC cells was assessed by two-dimensional gel electrophoresis (2-DE), followed by liquid chromatography and tandem mass spectrometry. The 2-DE assays revealed a global increase in protein expression in the EOC cells treated with CM. Nine proteins were identified from 11 selected protein spots with differential expression after treatment with CM from O-ADSCs. All the nine proteins have been linked to carcinoma and apoptosis, and the migration ability of tumor cells can be regulated by these proteins. Moreover, the upregulation of prohibitin and serine/arginine-rich splicing factor 1 in EOC cells treated with CM was further confirmed by quantitative real-time polymerase chain reaction. These results suggest that O-ADSCs affect the proteomic profile of EOC cells via paracrine mechanism in favor of EOC progression. [ABSTRACT FROM AUTHOR]

Background and Objectives: With an increased incidence of obesity in China, this study sought to investigate the correlation between serum 25-hydroxyvitamin D levels and adiposity phenotypes in Chinese adults from urban settings.Methods and Study Design: A total of 1277 subjects aged 20-82 years old were recruited into this cross-sectional study. Anthropometric parameters and blood biochemistry panels were measured. Statistical analysis using partial correlation, multivariable regression and covariance were performed to assess the impact of obesity parameters on serum 25-hydroxyvitamin D levels.Results: After adjustment for age and gender, serum25-hydroxyvitamin D levels were found to be inversely related to body mass index, waist circumference, waist/hip ratio, body fat, body fat percentage and waist fat to hip fat ratio. In multivariable regression analysis, serum 25-hydroxyvitamin D levels were negatively associated with waist circumference, waist/hip ratio, body fat, body fat percentage and waist fat/hip fat ratio (p<0.05), while there was no correlation with body mass index (p>0.05). After inclusion of body fat, body fat percentage and waist fat to hip fat ratio in one model, only waist fat to hip fat ratio remained significantly associated with serum 25-hydroxyvitamin D levels (p<0.05). The covariance analysis results showed that abdominal obesity subjects had lower serum 25-hydroxyvitamin D levels compared to the counterpart group, as defined by waist circumference or waist/hip ratio (p<0.05).Conclusion: Our results affirm the relationship between serum 25-hydroxyvitamin D levels and abdominal obesity, suggesting that adiposity phenotypes were strongly linked to serum 25-hydroxyvitamin D levels. [ABSTRACT FROM AUTHOR]

Human mesenchymal stem cells (MSCs) represent a novel carrier for gene therapy and apoptin is a potential tumor-selective apoptosis-inducing protein. In the present study, the anti-tumoral effect of MSCs modified with apoptin against lung carcinoma was evaluated. Apoptin protein was expressed in a prokaryotic expression system and purified by affinity chromatography. Subsequently, anti-apoptin antibody was prepared by immunizing BALB/c mice with purified apoptin protein. Human MSCs were isolated, amplified and transduced with lentiviral vectors encoding full-length apoptin, in which the secretory signal and protein transduction sequence were added into the amino terminus to assist apoptin in entering into target cells. The differentiation and apoptin expression of apoptin-modified MSCs were confirmed. Subsequently, the anti-tumor effect of apoptin-modified MSCs was measured in vitro and in vivo. Following modification with apoptin, MSCs retained their differentiation capacity, and successfully synthesized and secreted apoptin, which entered target cells and selectively induced lung cancer cell apoptosis through activating caspase-3. The percentage of tumor cells with activated caspase-3 in the apoptin-modified MSCs group was markedly higher than that in the MSCs group (16.5±2.9% at 24 h and 27.3±2.0% at 48 h vs. 3.4±1.1% at 24 h and 2.2±0.6% at 48 h). When injected into nude mice, apoptin-modified MSCs inhibited the growth of lung carcinoma compared with that in the control groups (0.14±0.02 g vs. 0.21±0.04 g vs. 0.31±0.05 g, P<0.05). The results of the present study provided preclinical support of apoptin-based cancer therapy with MSCs as cellular vehicles. [ABSTRACT FROM AUTHOR]

Background: Centrally necrotizing carcinoma of the breast (CNC) represents a newly-identified subset of breast cancer. The clinical and pathological characteristics of this breast cancer subtype are not yet completely understood. Methods: We assessed the clinicopathological characteristics of 73 cases of CNC and 30 control cases of high-grade infiltrating ductal carcinoma (IDC) with focal necrosis based on light microscopy and immunohistochemical staining for estrogen receptor, progesterone receptor, Cerb-B2/HER2, Ki-67, epidermal growth factor receptor, cytokeratin 5/6, smooth muscle actin, S-100 protein, p63 and CD10. Results: All the tumors showed extensive central necrotic or acellular zones with different degrees of fibrotic or hyaline material surrounded by ring-like or ribbon-like residual tumour tissue which were usually high-grade IDCs. The central necrotic zone accounted for at least 30% of the cross-sectional area of the tumor. Thirty-six cases (49.3%) showed a component of ductal carcinoma in situ. The tumorous stroma around the central necrotic zone was accompanied by myxoid matrix formation in 28 cases (40%). Lymphocytic infiltration was present in 53 cases (72.6%). Granulomatous reactions were detected at the periphery of the tumors in 49 cases (67.1%). Immunohistochemistry showed greater expression of basal-like markers (72.2%, 52 cases) than myoepithelial markers (60.6%, 43 cases), both of which were significantly higher than in controls (26.7%, 8 cases) (P < 0.001). According to molecular typing, most CNCs were basal-like subtype (37 cases, 50.7%). Follow-up data were available for 28 patients. Disease progression occurred in 11 patients. The combined rate of recurrence, distant metastasis or death was significantly higher in CNC patients compared with controls (P < 0.05). Conclusions: CNC was associated with distinctive clinicopathologic features mostly characterized as basal-like type. Its high proliferative activity, highly-aggressive biological behavior, and high rates of recurrence and metastasis, suggest that CNC should be classified as a new type of breast carcinoma. [ABSTRACT FROM AUTHOR]

Based on the characteristics of speech signal, this paper develops a new digital information hiding algorithm. The basic idea: according to the characteristics of human ear's insensitiveness to speech signal absolute phases, the paper makes full use of the short-time energy of speech signal to find the silence sections of the signal, then makes the absolute silence sections, and takes advantage of the absolute silence sections to create a number of ?independent sections?. By changing the absolute phases of the ?independent sections?, all sampling points of the ?independent sections? are inverted, the positive proportion of sampling points of these sections are changed accordingly, and thus those secret digital pieces of information are carried. The experiments show that the proposed algorithm has excellent properties in robustness and invisibility. [ABSTRACT FROM AUTHOR]

Background Hirudin is an anti-coagulation protein produced by the salivary glands of the medicinal leech Hirudomedicinalis. It is a powerful and specific thrombin inhibitor. The novel recombinant hirudin, RGD-hirudin, which contains an RGD motif, competitively inhibits the binding of fibrinogen to GPIIb/IIIa on platelets, thus inhibiting platelet aggregation while maintaining its anticoagulant activity. Results Recombinant RGD-hirudin and six mutant variants (Y3A, S50A, Q53A, D55A, E57A and I59A), designed based on molecular simulations, were expressed in Pichia pastoris. The proteins were refolded and purified to homogeneity as monomers by gel filtration and anion exchange chromatography. The anti-thrombin activity of the six mutants and RGD-hirudin was tested. Further, we evaluated the binding of the mutant variants and RGD-hirudin to thrombin using BIAcore surface plasmon resonance analysis (SPR). Kinetics and affinity constants showed that the KD values of all six mutant proteins were higher than that of RGD-hirudin. Conclusions These findings contribute to a novel understanding of the interaction between RGD-hirudin and thrombin. [ABSTRACT FROM AUTHOR]

Mucinous tubular and spindle cell carcinoma (MTSC) was first recognized as a specific entity in the World Health Organization 2004 classification. The "classic" tumor presentation includes an extracellular blue-gray mucinous/myxoid matrix accompanying the typical tubular and spindle cell epithelial components. Tubules are lined by cuboidal to columnar cells with bland nuclei, central small to medium sized nucleoli, and few to no mitoses. By expanding the histologic spectrum, a number of studies highlighted the distinction between MTSC and solid variant of papillary renal cell carcinoma (sPRCC), although controversy still exists. Here, we evaluated two cases of MTSC and compared two cases of sPRCC by light microscopy, special staining, immunohistochemical staining and fluorescence in situ hybridization (FISH). We found that morphologic and immunophenotyping features showed more overlap between MTSC and sPRCC. In addition, gains of chromosomes 7 and 17 and loss of Y, which are characteristic of PRCC, were observed in two cases of sPRCC and one case of MTSC, suggesting that MTSC is similar to sPRCC or may be a subtype of PRCC. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_194 [ABSTRACT FROM AUTHOR]

In the collective-risk social dilemma, players lose their personal endowments if contributions to the common pool are too small. This fact alone, however, does not always deter selfish individuals from defecting. The temptations to free ride on the prosocial efforts of others are strong because we are hardwired to maximize our own fitness regardless of the consequences which might have for the public good. Here we show that the addition of risky assets to the personal endowments, both of which are lost if the collective target is not reached, can contribute to solving the collective-risk social dilemma. In infinite well-mixed populations, risky assets introduce new stable and unstable mixed steady states, whereby the stable mixed steady state converges to full cooperation as either the risk of collective failure or the amount of risky assets increases. Similarly, in finite well-mixed populations, the introduction of risky assets enforces configurations where cooperative behavior thrives. In structured populations cooperation is promoted as well, but the distribution of assets among the groups is crucial. Surprisingly, we find that the completely rational allocation of assets only to the most successful groups is not optimal, and this regardless of whether the risk of collective failure is high or low. Instead, in low-risk situations bounded rational allocation of assets works best, while in high-risk situations the simplest uniform distribution of assets among all the groups is optimal. These results indicate that prosocial behavior depends sensitively on the potential losses individuals are likely to endure if they fail to cooperate. [ABSTRACT FROM AUTHOR]

The underground structure in coral sand is threatened by earthquake. The special dynamic characteristics of coral sand were realized by finite difference program. Specifically, the stress-strain loops, shear modulus attenuation and hysteresis behaviour of coral sand were simulated using hysteresis damping. On this basis, numerical models were established to study the seismic response of the rectangular underground structure in coral sand, and the fluid-solid coupling and soil-structure interaction were considered. The results illustrate that the increasing relative density of coral sand foundation reduces the excess pore water pressure (EPWP), but amplifies the horizontal dynamic soil pressure of the coral sand-underground structure system. The increase in the permeability coefficient of coral sand reduces the EPWP accumulation, which leads to an increase of the stiffness and a decrease of the acceleration amplification of coral sand sites. [ABSTRACT FROM AUTHOR]

Background: Aminoacyl-tRNA synthetases (AARSs) catalyze the first step of protein synthesis. Emerging evidence indicates that AARSs may have additional functions, playing a role in signal transduction pathways regulating thrombopoiesis and inflammation. Recombinant human tyrosyl-tRNA synthetase (rhTyrRS) is engineered with a single amino acid substitution that unmasks its cytokine activity. An industrial production method that provides high yield as well as high purity, quality, and potency of this protein is required for preclinical research. Results: We expressed codon-optimized rhTyrRS in Escherichia coli under fermentation conditions. Soluble protein was purified by a three-step purification method using cation exchange chromatography, gel filtration chromatography, and anion exchange chromatography. We also established a method to test the biological activity of rhTyrRS by measuring aminoacylation and IL-8 release in rhTyrRS-treated HL-60 cells. Conclusions: The characterization of purified rhTyrRS indicated that this protein can be used in pharmacodynamic and pharmacokinetic studies. [ABSTRACT FROM AUTHOR]

Water-soluble phenol and phenolic compounds were generally removed via advanced oxidation processes. A novel semiconductor catalyst, CT, was the first-time employed in the present study to degrade phenol and catechol. The phenolic compounds (initial concentration of 88mg L-1) were completely mineralized by the CT catalytic nanoparticles (1%) within 15 days, under acidic condition and with the presence ofmild UV radiation (15w, the emitted wavelength is 254 nmand the light intensity <26 μw/cm2). Under the same reaction condition, 1% TiO2 (mixture of rutile and anatase, nanopowder, <100 nm) and H2O2 had lower removal efficiency (phenol: <42%; catechol: <60%), whereas the control (without addition of catalysts/H2O2) only showed <12% removal. The processes of phenol/catechol removal by CT followed pseudo-zero-order kinetics. The aromatic structures absorbed the UV energy and passed to an excited state, which the CT worked on.The pollutants were adsorbed on the CT's surface and oxidized via charge-transfer and hydroxyl radical generation by CT. Given low initial concentrations, a circumstance encountered in wastewater polishing, the current set-up should be an efficient and less energy- and chemical-consumptive treatment method. [ABSTRACT FROM AUTHOR]

Amounts of empirical evidence, ranging from microbial cooperation to collective hunting, suggests public goods produced often nonlinearly depend on the total amount of contribution. The implication of such nonlinear public goods for the evolution of cooperation is not well understood. There is also little attention paid to the divisibility nature of individual contribution amount, divisible vs. non-divisible ones. The corresponding strategy space in the former is described by a continuous investment while in the latter by a continuous probability to contribute all or nothing. Here, we use adaptive dynamics in finite populations to quantify and compare the roles nonlinearity of public-goods production plays in cooperation between these two contribution mechanisms. Although under both contribution mechanisms the population can converge into a coexistence equilibrium with an intermediate cooperation level, the branching phenomenon only occurs in the divisible contribution mechanism. The results shed insight into understanding observed individual difference in cooperative behavior. [ABSTRACT FROM AUTHOR]

Cell therapy has been extensively investigated in heart disease but less so in the kidney. We considered whether cell therapy also might be useful in diabetic kidney disease. Cognizant of the likely need for autologous cell therapy in humans, we sought to assess the efficacy of donor cells derived from both healthy and diabetic animals. Eight-week-old db/db mice were randomized to receive a single intravenous injection of PBS or 0.5 x 106 early-outgrowth cells (EOCs) from db/m or db/db mice. Effects were assessed 4 weeks after cell infusion. Untreated db/db mice developed mesangial matrix expansion and tubular epithelial cell apoptosis in association with increased reactive oxygen species (ROS) and overexpression of thioredoxin interacting protein (TxnIP). Without affecting blood glucose or blood pressure, EOCs not only attenuated mesangial and peritubular matrix expansion, as well as tubular apoptosis, but also diminished ROS and TxnIP overexpression in the kidney of db/db mice. EOCs derived from both diabetic db/db and nondiabetic db/m mice were equally effective in ameliorating kidney injury and oxidative stress. The similarly beneficial effects of cells from healthy and diabetic donors highlight the potential of autologous cell therapy in the related clinical setting. [ABSTRACT FROM AUTHOR]

A novel recombinant hirudin, RGD-hirudin, inhibits the activity of thrombin and the aggregation of platelets. Here, we successfully expressed 15N, 13C-labeled RGD-hirudin in Pichia pastoris in a fermenter. The protein was subsequently purified to yield sufficient quantities for structural and functional studies. The purified protein was characterized by HPLC and MALDI-TOF mass spectroscopy. Analysis revealed that the protein was pure and uniformly labeled with 15N and 13C. A bioassay showed that the anti-thrombin activity and the anti-platelet aggregation ability of the labeled protein were the same as those of unlabeled RGD-hirudin. Multidimensional heteronuclear NMR spectroscopy has been used to determine almost complete backbone 15N, 13C and ¹H resonance assignments of the r-RGD-Hirudin. The 15N-¹H HSQC spectrum of uniformly 15N, 13C-labeled RGD-hirudin allowed successful assignment of the signals. Examples of the quality of the data are provided for the 15N-¹H correlation spectrum, and by selected planes of the CBCA(CO)NH, CBCANH, and HNCO experiments. These results provide a basis for further studies on the structure-function relationship of RGD-hirudin with thrombin and platelets [ABSTRACT FROM AUTHOR]

A recent experimental study [Traulsen et al., Proc. Natl. Acad. Sci. 107, 2962 (2010)] shows that human strategy updating involves both direct payoff comparison and the cost of switching strategy, which is equivalent to inertia. However, it remains largely unclear how such a predisposed inertia affects 2x2 games in a well-mixed population of finite size. To address this issue, the "inertia bonus" (strategy switching cost) is added to the learner payoff in the Fermi process. We find how inertia quantitatively shapes the stationary distribution and that stochastic stability under inertia exhibits three regimes, with each covering seven regions in the plane spanned by two inertia parameters. We also obtain the extended "1/3" rule with inertia and the speed criterion with inertia; these two findings hold for a population above two. We illustrate the above results in the framework of the Prisoner's Dilemma game. As inertia varies, two intriguing stationary distributions emerge: the probability of coexistence state is maximized, or those of two full states are simultaneously peaked. Our results may provide useful insights into how the inertia of changing status quo acts on the strategy evolution and, in particular, the evolution of cooperation. [ABSTRACT FROM AUTHOR]

The effects of enalapril and sodium depletion on renin synthesis and secretion were studied in mice with a left hydronephrotic kidney caused by unilateral ureteral ligation (UUL). In the control animals, there was no difference in plasma renin concentration between the right and left renal veins. In mice with left ureteral ligation, the renin concentration in the vein draining the hydronephrotic kidney was similar to or lower than that in the aorta under control conditions and after either stimulation with enalapril or depletion of sodium. Enalapril and sodium restriction increased plasma renin concentration, and this increase was due to secretion from the nonhydronephrotic kidney. The renin concentration per gram of kidney tissue and the mRNA for renin per gram of kidney tissue were similar in both the control and hydronephrotic kidney, and the values rose 3-4-fold in both kidneys after enalapril or sodium depletion. Immunostaining for renin confirmed these findings and indicated that renin per glomerulus was higher in the hydronephrotic kidney. Thus, removal or reduction of angiotensin II activity or depletion of sodium stimulated synthetic activity to a similar extent in the normal and hydronephrotic kidneys; however, secretion from the kidney without a macula densa (hydronephrotic) was not increased. Thus, the signals that control synthesis and secretion are different, and for these stimuli, secretion appears to require an intact macula densa. [ABSTRACT FROM AUTHOR]

The stress of nebulization has been shown to alter the properties of liposomal drugs. What has not been demonstrated is whether nebulized liposomes differ as a function of droplet size. Because droplet size influences lung deposition, liposomes with different properties could be deposited in different areas of the lung (e.g., central vs. peripheral). In this report, a liposomal amikacin formulation (Arikace™, a registered trademark of Transave, Inc., Monmouth Junction, NJ) that is being developed as an inhaled treatment for gram negative infections was aerosolized with an eFlow®(registered trademark of PARI, GmbH, Munich, Germany) nebulizer, reclaimed from the various stages of an Andersen cascade impactor (ACI) and analyzed for lipid-to-drug (LD) (ww) ratio, amikacin retention, and liposome size. For the nebulized solution, 99.7 of the total deposited drug was found on ACI stages 0 through 5, which have cutoff diameters of 9, 5.8, 4.7, 3.3, 2.1, and 1.1 μm, respectively. Properties were found to differ for drug reclaimed on stage 0 compared stages 1–5, which were not different from one another. For drug found on stages 1–5 (97 of total drug), the averages (n 3) for LD, percent encapsulated amikacin, and liposome mean diameter ranged from 0.59 to 0.68 (ww), 71 to 75, 248 to 282 nm, respectively. Drug found on stage 0 (2.8 of total drug) had an average LD ratio of 0.51 and average liposome mean diameter of 375 nm. Examination of another batch of liposomal amikacin revealed no statistically significant differences between drug reclaimed on stages 0–5. Although a droplet size dependence was noted for one batch of Arikace™aerosolized with the eFlow®, the effect was considered to be inconsequential because the fraction in doubt represented nonrespirable particles >9 μm and accounted for <3 of the total deposited dose. The methodology applied here appears useful in evaluating aerosolized liposome systems. However, our results should not be assumed to apply to other liposomedrug compositions and nebulizers. [ABSTRACT FROM AUTHOR]

Membrane-bound phosphoinositides are signalling molecules that have a key role in vesicle trafficking in eukaryotic cells. Proteins that bind specific phosphoinositides mediate interactions between membrane-bounded compartments whose identity is partially encoded by cytoplasmic phospholipid tags. Little is known about the localization and regulation of mammalian phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P2), a phospholipid present in small quantities that regulates membrane trafficking in the endosome–lysosome axis in yeast. Here we describe a multi-organ disorder with neuronal degeneration in the central nervous system, peripheral neuronopathy and diluted pigmentation in the ‘pale tremor’ mouse. Positional cloning identified insertion of ETn2β (early transposon 2β) into intron 18 of Fig4 (A530089I17Rik), the homologue of a yeast SAC (suppressor of actin) domain PtdIns(3,5)P2 5-phosphatase located in the vacuolar membrane. The abnormal concentration of PtdIns(3,5)P2 in cultured fibroblasts from pale tremor mice demonstrates the conserved biochemical function of mammalian Fig4. The cytoplasm of fibroblasts from pale tremor mice is filled with large vacuoles that are immunoreactive for LAMP-2 (lysosomal-associated membrane protein 2), consistent with dysfunction of the late endosome–lysosome axis. Neonatal neurodegeneration in sensory and autonomic ganglia is followed by loss of neurons from layers four and five of the cortex, deep cerebellar nuclei and other localized brain regions. The sciatic nerve exhibits reduced numbers of large-diameter myelinated axons, slowed nerve conduction velocity and reduced amplitude of compound muscle action potentials. We identified pathogenic mutations of human FIG4 (KIAA0274) on chromosome 6q21 in four unrelated patients with hereditary motor and sensory neuropathy. This novel form of autosomal recessive Charcot–Marie–Tooth disorder is designated CMT4J. [ABSTRACT FROM AUTHOR]

A new complex of lanthanum picrate with N , N ′-diethyl- N , N ′-diphennyl-3-oxapentanediamide (L) was synthesized and its structure determined by X-ray diffraction measurements. It crystallizes as the ten-coordinate complex La(pic) 3 L 2 in the triclinic space group $ {\it P \bar 1} $ with a = 12.140(2), b = 14.250(2), c = 20.333(2) Å, α = 101.400(10), β = 99.390(10), γ = 102.400(10)°, U = 3289.1(8) Å 3 , Z = 2, D c = 1.519 g cm -3 . The complex possesses a novel ladder-like 2-D supramolecular structure directed by π-π interactions. [ABSTRACT FROM AUTHOR]

The title complex Eu(Pic) 3 (TTD) crystallizes in space group Pcab with a = 23.714(4), b = 29.245(6), c = 32.035(8) Å, V = 22216(7) Å 3 , Z = 16, D c = 1.63 g cm -1 , μ = 12.5 cm -1 , F (000) = 10976 and its structure was solved and refined to R = 0.083. Two crystallographically different Eu(Pic) 3 (TTD) units, in which the coordination numbers of two central ions (Eu1 and Eu2) are nine and ten, respectively, are present in the asymmetric unit. In the 7 F 0 → 5 D 0 excitation spectrum of the complex, there are two sharp peaks at 578.5 and 579.0 nm indicating that the complex has two Eu(III) sites. Two different patterns in the 5 D 0 → 7 F j (j = 1-4) luminescence spectrum have been observed (selectively excited 5 D 0 ), which further reveals the existence of two Eu(III) sites compatible with the result of the structure determination. [ABSTRACT FROM AUTHOR]

In ovarian cancer patients, tumor fibrosis and angiotensin-driven fibrogenic signaling have been shown to inversely correlate with survival. We sought to enhance drug delivery and therapeutic efficacy by remodeling the dense extracellular matrix in two orthotopic human ovarian carcinoma xenograft models. We hypothesized that targeting the angiotensin signaling axis with losartan, an approved angiotensin system inhibitor, could reduce extracellular matrix content and the associated "solid stress," leading to better anticancer therapeutic effect. We report here four translatable findings: (i) losartan treatment enhances the efficacy of paclitaxel--a drug used for ovarian cancer treatment--via normalizing the tumor microenvironment, resulting in improved vessel perfusion and drug delivery; (ii) losartan depletes matrix via inducing antifibrotic miRNAs that should be tested as candidate biomarkers of response or resistance to chemotherapy; (iii) although losartan therapy alone does not reduce tumor burden, it reduces both the incidence and the amount of ascites formed; and (iv) our retrospective analysis revealed that patients receiving angiotensin system inhibitors concurrently with standard treatment for ovarian cancer exhibited 30 mo longer overall survival compared with patients on other antihypertensives. Our findings provide the rationale and supporting data for a clinical trial on combined losartan and chemotherapy in ovarian cancer patients. [ABSTRACT FROM AUTHOR]

This study assessed the hypothesis that the protein levels of high mobility group box 1 (HMGB1) and hepsin can be used as markers for diagnosis and prognosis in cervical carcinoma. Seventy patients with cervical cancer who were hospitalized in Xuzhou Central Hospital from May 2008 to June 2010 and underwent surgical treatment were selected for the observation group. At the same time, 20 patients with cervical benign lesions who underwent tumor stripping or accessory resection were selected for the control group. Immunohistochemical (SP) detection methods were used to detect hepsin and HMGB1 protein levels in tissues. The positive rates of HMGB1 cells in normal, paracancerous and cancerous cervical tissues were 5.0% (1/20), 22.9% (16/70) and 95.7% (67/70) (F=24.581, P=0.001) respectively. The positive rates of hepsin in normal, paracancerous and cancerous cervical tissues were respectively 10% (2/20), 61% (43/70) and 90% (63/70) (F=11.538, P=0.001). The HMGB1 expression level was related to the degree of tumor differentiation, lymph node metastasis and TNM stage (P<0.05). While the level of hepsin expression was related to the degree of tumor differentiation, invasion depth, lymph node metastasis and TNM stage (P<0.05). Furthermore, a positive correlation between the levels of hepsin and HMGB1 was found (r=15.27, P<0.05). The overall 5-year survival rates of patients with high expression of HMGB1 (+++) and low expression of HMGB1 (+ to ++) were respectively 51.2 and 29.2% (HR=11.637, 95% CI=4.351‑38.213; P=0.002). The overall 5-year survival rates of patients with high hepsin expression (+++) and low hepsin expression (+ to ++) were respectively 41.3 and 35.3% (HR=10.143, 95% CI=4.285‑33.275; P=0.006). Based on our results, the higher the levels of expression of hepsin and HMGB1 in tissues the higher the degree of invasiveness of the cervical cancers, and the worse the prognoses for the patient. [ABSTRACT FROM AUTHOR]

The increasing demand for safe and effective treatments of chronic pain has promoted the investigation of novel analgesic drugs. Some herbals have been known to be able to relieve pain, while the chemical basis and target involved in this process remained to be clarified. The current study aimed to find anti-nociceptive candidates targeting transient receptor potential ankyrin 1 (TRPA1), a receptor that implicates in hyperalgesia and neurogenic inflammation. In the current study, 156 chemicals were tested for blocking HEK293/TRPA1 ion channel by calcium-influx assay. Docking study was conducted to predict the binding modes of hit compound with TRPA1 using Discovery Studio. Cytotoxicity in HEK293 was conducted by Cell Titer-Glo assay. Additionally, cardiotoxicity was assessed via xCELLigence RTCA system. We uncovered that cardamonin selectively blocked TRPA1 activation while did not interact with TRPV1 nor TRPV4 channel. A concentration-dependent inhibitory effect was observed with IC50 of 454 nM. Docking analysis of cardamonin demonstrated a compatible interaction with A-967079-binding site of TRPA1. Meanwhile, cardamonin did not significantly reduce HEK293 cell viability, nor did it impair cardiomyocyte constriction. Our data suggest that cardamonin is a selective TRPA1 antagonist, providing novel insight into the target of its anti-nociceptive activity. [ABSTRACT FROM AUTHOR]

Phosphatidylinositol (3,5)-bisphosphate [PtdIns(3,5)P2] is a critical signaling phospholipid involved in endolysosome homeostasis. It is synthesized by a protein complex composed of PIKfyve, Vac14, and Fig4. Defects in PtdIns(3,5)P2 synthesis underlie a number of human neurological disorders, including Charcot-Marie-Tooth disease, child onset progressive dystonia, and others. However, neuron-specific functions of PtdIns(3,5) P2 remain less understood. Here, we show that PtdIns(3,5)P2 pathway is required to maintain neurite thickness. Suppression of PIKfyve activities using either pharmacological inhibitors or RNA silencing resulted in decreased neurite thickness. We further find that the regulation of neurite thickness by PtdIns(3,5)P2 is mediated by NSG1/NEEP21, a neuron-specific endosomal protein. Knockdown of NSG1 expression also led to thinner neurites. mCherry-tagged NSG1 colocalized and interacted with proteins in the PtdIns(3,5)P2 machinery. Perturbation of PtdIns(3,5)P2 dynamics by overexpressing Fig4 or a PtdIns(3,5)P2-binding domain resulted in mislocalization of NSG1 to nonendosomal locations, and suppressing PtdIns(3,5)P2 synthesis resulted in an accumulation of NSG1 in EEA1-positive early endosomes. Importantly, overexpression of NSG1 rescued neurite thinning in PtdIns(3,5)P2-deficient CAD neurons and primary cortical neurons. Our study uncovered the role of PtdIns(3,5)P2 in the morphogenesis of neurons, which revealed a novel aspect of the pathogenesis of PtdIns(3,5)P2-related neuropathies. We also identified NSG1 as an important downstream protein of PtdIns(3,5)P2, which may provide a novel therapeutic target in neurological diseases. [ABSTRACT FROM AUTHOR]

To improve the bonding strength between adhesive and enhance the performance of composite board made from corn stalk rinds, a method for preparing three-layer composite boards was proposed. Accordingly, corn stalk rinds with the epidermis removed, were used as the core layer, while crushed aggregates from the epidermis were used as the surface layer of the composite board. Single-factor and orthogonal experiments were conducted to analyze the effects of the sampling height of corn stalk rinds, the surface layer proportions, and the hot-pressing temperature and time on the physico-mechanical properties of composite board. The resulting composite board from corn stalk rinds showed enhanced properties, except for the internal bond strength (P < 0.01). The physical properties of the composite board were significantly improved (P < 0.01) by removing the crushed aggregates of the epidermis, forming a single layer of composite board. The optimal parameters were as follows: the sampling height below the ear part of the corn stalk rinds; 12% surface layers; 150 °C hot-pressing temperature; and 6 min time. Under these conditions, the physico-mechanical properties of the composite board met the requirement level for particleboard. This research supports the use of corn stalk rinds as composite boards. [ABSTRACT FROM AUTHOR]

In this study, the dynamic characteristics of a plate-like micro-cantilever beam attached with multiple concentrated masses are studied. The vibration modes of the cantilever plate are represented by combinations of beam functions. Using classical mechanics (the effect of size is not considered) and the corrected Cosserat's theorem (the effect of size is considered), we employ the Lagrange equations to establish a dynamic model of the plate-like micro-cantilever beam attached with multiple concentrated masses. The accuracy of the model proposed in this paper is verified by comparing with the results of published literature. Then, the natural frequencies of the cantilever plates are calculated with self-compiled algorithms, and the results of the plates with 1-5 masses are displayed. The results are in high accordance with the exact solution, and all errors are within 0.5%. The analysis shows that the proposed model and analysis method converges quickly and is highly efficient. In addition, the effects of characteristic lengths, Poisson's ratios and plate thickness on the microcantilever plate's resonant frequency for the first five modes are analyzed. [ABSTRACT FROM AUTHOR]

Background: Plasmin is a serine protease that plays a critical role in fibrinolysis, which is a process that prevents blood clots from growing and becoming problematic. Recombinant human microplasminogen (rhμPlg) is a derivative of plasmin that solely consists of the catalytic domain of human plasmin and lacks the five kringle domains found in the native protein. Developing an industrial production method that provides high yields of this protein with high purity, quality, and potency is critical for preclinical research. Results: The human microplasminogen gene was cloned into the pPIC9K vector, and the recombinant plasmid was transformed into Pichia pastoris strain GS115. The concentration of plasmin reached 510.1 mg/L of culture medium. Under fermentation conditions, the yield of rhμPlg was 1.0 g/L. We purified rhμPlg to 96 % purity by gel-filtration and cation-exchange chromatography. The specific activity of rhμPlg reached 23.6 U/mg. The Km of substrate hydrolysis by recombinant human microplasmin was comparable to that of human plasmin, while rhμPlm had higher kcat/Km values than plasmin. The high purity and activity of the rhμPlg obtained here will likely prove to be a valuable tool for studies of its application in thrombotic diseases and vitreoretinopathies. Conclusions: Reliable rhμPlg production (for use in therapeutic applications) is feasible using genetically modified P. pastoris as a host strain. The successful expression of rhμPlg in lays a solid foundation for its downstream application. [ABSTRACT FROM AUTHOR]

Tanshinone IIA (Tan IIA) is one of the major fat-soluble ingredients in Salvia miltiorrhiza which has been widely used for various inflammatory conditions associated with cardiovascular and cerebrovascular disorders. However, the underlying anti-inflammatory mechanisms of Tan IIA are incompletely understood. The purpose of this study was to illuminate the anti-inflammatory mechanism of Tan IIA based on the protein interaction network (PIN) analysis. A PIN of Tan IIA was constructed with 281 nodes and 814 interactions and analyzed by gene ontology (GO) enrichment analysis based on Markov Cluster algorithm (MCL). Three modules were associated with anti-inflammatory actions. The most interesting finding of this study was that the anti-inflammatory effect of Tan IIA may be partly attributable to the mediate activation of TRAF2, TRAF3 and TRAF6, to inhibit the toll-like receptor signaling pathway and combine with AGER. Therefore, the module-based network analysis approach will be a new method for better understanding the anti-inflammatory mechanism of Tan IIA. [ABSTRACT FROM AUTHOR]

Cells in which insulin is not required for glucose uptake are susceptible to the long-term complications of diabetes. Even in these tissues, however, the major perturbations that would otherwise be engendered by the greatly increased intracellular glucose concentration are mollified by adaptive changes in the enzymes of intermediary metabolism. These include allosteric regulation, product inhibition, and covalent modification as well as alterations in gene transcription. More recently, advances in proteomic technology have shown that reversible acetylation of the 3-amino group of lysine provides an additional means of modulating protein function and, in particular, enzyme activity. Here, we explored the extent of protein acetylation in an organ susceptible to the long-term complications of diabetes, examining the kidneys of rats with streptozotocin-induced diabetes and kidney cells exposed to high glucose. Using high-resolution mass spectrometry coupled with immunoaffinity enrichment, we identified 47 lysineacetylated proteins in the kidneys of diabetic rats compared with 11 in control kidneys. Bioinformatic interrogation of the acetylome from diabetic animals showed a predominance of metabolic pathway involvement including the citrate acid cycle, glycolysis/gluconeogenesis, and metabolism of branched chain amino acids. Increased lysine acetylation was also noted in mesangial and tubular cells exposed to 25 mmol/L compared with 5.6 mmol/L glucose. These findings highlight acetylation as a posttranslational modification affecting numerous proteins. Current drug discovery efforts to develop small molecule inhibitors and activators of various lysine acetylases and deacetylases offer a new potential strategy to reduce the likelihood of diabetes complications. [ABSTRACT FROM AUTHOR]

Background Nasopharyngeal carcinoma (NPC) is a common malignant tumor observed in the populations of southern China and Southeast Asia. However, little is known about the effects of purinergic signal on the behavior of NPC cells. This study analyzed the effects of ATP on the growth and migration of NPC cells, and further investigated the potential mechanisms during the effects. Methods Cell viability was estimated by MTT assay. Transwell assay was utilized to assess the motility of NPC cells. Cell cycle and apoptosis were detected by flow cytometry analysis. Changes in OPN, P2Y2 and p65 expression were assessed by western blotting analysis or immunofluorescence. The effects of ATP and P2Y2 on promoter activity of OPN were analyzed by luciferase activity assay. The binding of p65 to the promoter region of OPN was examined by ChIP assay. Results An MTT assay indicated that ATP inhibited the proliferation of NPC cells in time- and dosedependent manners, and a Transwell assay showed that extracellular ATP inhibited the motility of NPC cells. We further investigated the potential mechanisms involved in the inhibitory effect of extracellular ATP on the growth of NPC cells and found that extracellular ATP could reduce Bcl-2 and p-AKT levels while elevating Bax and cleaved caspase-3 levels in NPC cells. Decreased levels of p65 and osteopontin were also detected in the ATP-treated NPC cells. We demonstrated that extracellular ATP inhibited the growth of NPC cells via p65 and osteopontin and verified that P2Y2 overexpression elevated the inhibitory effect of extracellular ATP on the proliferation of NPC cells. Moreover, a dual luciferase reporter assay showed that the level of osteopontin transcription was inhibited by extracellular ATP and P2Y2. ATP decreased the binding of p65 to potential sites in the OPN promoter region in NPC cells. Conclusion This study indicated that extracellular ATP inhibited the growth of NPC cells via P2Y2, p65 and OPN. ATP could be a promising agent serving as an adjuvant in the treatment of NPC. [ABSTRACT FROM AUTHOR]

Mutations that cause defects in levels of the signaling lipid phosphatidylinositol 3,5-bisphosphate [PI(3,5)P₂] lead to profound neurodegeneration in mice. Moreover, mutations in human FIG4 predicted to lower PI(3,5)P₂ levels underlie Charcot-Marie-Tooth type 4J neuropathy and are present in selected cases of amyotrophic lateral sclerosis. In yeast and mammals, PI(3,5)P₂ is generated by a protein complex that includes the lipid kinase Fab1/Pikfyve, the scaffolding protein Vac14, and the lipid phosphatase Fig4. Fibroblasts cultured from Vac14-/- and Fig4-/- mouse mutants have a 50% reduction in the levels of PI(3,5)P₂, suggesting that there may be PIKfyve-independent pathways that generate this lipid. Here, we characterize a Pikfyve gene-trap mouse (Pikfyveβ-geo/β-geo), a hypomorph with ~10% of the normal level of Pikfyve protein. shRNA silencing of the residual Pikfyve transcript in fibroblasts demonstrated that Pikfyve is required to generate all of the PI(3,5)P₂ pool. Surprisingly, Pikfyve also is responsible for nearly all of the phosphatidylinositol-5-phosphate (PI5P) pool. We show that PI5P is generated directly from PI(3,5)P₂, likely via 3'-phosphatase activity. Analysis of tissues from the Pikfyveβ-geo/β-geo mouse mutants reveals that Pikfyve is critical in neural tissues, heart, lung, kidney, thymus, and spleen. Thus, PI(3,5)P₂ and PI5P have major roles in multiple organs. Understanding the regulation of these lipids may provide insights into therapies for multiple diseases. [ABSTRACT FROM AUTHOR]

"Voting with feet" describes the prominent social phenomenon that people tend to move away from deteriorating neighborhoods and search for and join prosperous groups. To quantify the role this kind of expectation-driven migration plays in the evolution of cooperation, here we study a simple yet effective model of cooperation based on spatial public goods games. The population structure is characterized by a square lattice with some nodes being left empty. Individuals have expectations toward their current habitats. Dissatisfied players, whose expectation is not met after interacting with all directly connected neighbors, tend to abstain from the groups of low quality by moving away and explore the physical niches of avail. How fast interaction happens relatively to selection is regulated by the time-scale ratio of game interaction to natural selection. Under strong selection, simulation results show that cooperation is greatly improved for either low, moderate, or high expectations compared to whenever the expectation-driven migration is absent. Further explorations reveal that neither too high nor too low but rather a combination of moderate expectations and rapid interaction establishes cooperation for a moderate public goods enhancement factor. There exists an optimal interval of expectation level most favoring the evolution of cooperation as the required time-scale ratio is minimized. [ABSTRACT FROM AUTHOR]

Self-associated protein aggregates or cross-linked protein conjugates are, in general, more immunogenic than oligomeric or monomeric forms. In particular, the immunogenicity in mice of a recombinant malaria transmission blocking vaccine candidate, the ookinete specific Plasmodium falciparum 25 kDa protein (Pfs25), was increased more than 1000-fold when evaluated as a chemical cross-linked protein-protein conjugate as compared to a formulated monomer. Whether alternative approaches using protein complexes improve the immunogenicity of other recombinant malaria vaccine candidates is worth assessing. In this work, the immunogenicity of the recombinant 42 kDa processed form of the P. falciparum merozoite surface protein 1 (MSP142) was evaluated as a self-associated, non-covalent aggregate and as a chemical cross-linked protein-protein conjugate to ExoProtein A, which is a recombinant detoxified form of Pseudomonas aeruginosa exotoxin A. MSP142 conjugates were prepared and characterized biochemically and biophysically to determine their molar mass in solution and stoichiometry, when relevant. The immunogenicity of the MSP142 self-associated aggregates, cross-linked chemical conjugates and monomers were compared in BALB/c mice after adsorption to aluminum hydroxide adjuvant, and in one instance in association with the TLR9 agonist CPG7909 with an aluminum hydroxide formulation. Antibody titers were assessed by ELISA. Unlike observations made for Pfs25, no significant enhancement in MSP142 specific antibody titers was observed for any conjugate as compared to the formulated monomer or dimer, except for the addition of the TLR9 agonist CPG7909. Clearly, enhancing the immunogenicity of a recombinant protein vaccine candidate by the formation of protein complexes must be established on an empirical basis. [ABSTRACT FROM AUTHOR]

Background: Recent research has implicated that mutations in the neurexin-1 (NRXN1) gene on chromosome 2p16.3 might play a role in schizophrenia, autism, and nicotine dependence. In order to explore the association of NRXN1 polymorphisms with schizophrenia, we made a case-control association study in Chinese Han population. Methods: We examined six tag single nucleotide polymorphisms (SNPs) spanning 116.7 kb of NRXN1 in 768 schizophrenic patients and 738 healthy control subjects. The association of NRXN1 polymorphisms with schizophrenia and the age-at-onset of this disease were explored. Results: Our results showed that four SNPs of NRXN1 gene were significantly associated with schizophrenia (rs10490168: G > A, p = 0.017; rs2024513: A > G, p = 0.006; rs13382584: T > C, p = 0.009; and rs1558852: G > A, p = 0.031). Furthermore, the association of SNP rs2024513 with schizophrenia remained significance after the Bonferroni correction. Haplotypes consisting of above six SNPs also showed significantly associated with schizophrenia (global chi-square = 14.725, p = 0.022). A protective haplotype AGTGCA remained associated with schizophrenia, even after 10,000 permutation tests (empirical p-value = 0.043). However, we did not find any association with age-atonset of schizophrenia with NRXN1 polymorphisms. Conclusions: Our findings suggest that NRXN1 might represent a major susceptibility gene for schizophrenia in Chinese Han population. [ABSTRACT FROM AUTHOR]

To evaluate effects of microwave ablation with a 2,450-MHz internally cooled-shaft antenna in animal experiments and in a clinical study. Microwave ablation was performed using a cooled-shaft antenna in eight in vivo (36 ablations) porcine livers. The coagulation diameters achieved in different microwave ablation parameter groups were compared. Sixty patients (44 men, 16 women; mean age 53 years) with 96, 1–8 cm (mean 3.20 ± 0.17 cm) liver cancers were treated with the same microwave ablation technique. Complete ablation (CA), local tumor progression (LTP) rates and complications were determined. In vivo livers, short axis diameter correlated with the coagulation duration in a sigmoidal curve fashion (60-W group R2 = 0.76, 80-W group R2 = 0.87), with a relative plateau achieved within 10 min for power settings of 60 or 80 W. Within 10 min in the 60 and 80-W groups, respectively, 89 and 85.76% of maximum short axis diameter were achieved. CA rates in small (3.0 cm), intermediate (3.1–5.0 cm) and large (5.1–8.0 cm) liver cancers were 96.43% (54/56), 92.31% (24/26) and 78.57% (11/14), respectively. During a mean follow-up period of 17.17 ± 6.52 months, LTP occurred in five (5.21%) treated cancers. There was no significant difference in the CA and LTP rate between the HCC and liver metastasis patient subgroups ( P > 0.05). The short axis diameter enlargement has a relative plateau within 10 min by fixing power output to 60 or 80 W, using the 2,450-MHz internally cooled-shaft antenna in vivo porcine livers. Effective local tumor control was achieved during one microwave ablation session. [ABSTRACT FROM AUTHOR]

Polarized expansion of root hair cells in Arabidopsis thaliana is improperly controlled in root hair-defective rhd4-1 mutant plants, resulting in root hairs that are shorter and randomly form bulges along their length. Using time-lapse fluorescence microscopy in rhd4-1 root hairs, we analyzed membrane dynamics after labeling with RabA4b, a marker for polarized membrane trafficking in root hairs. This revealed stochastic loss and recovery of the RabA4b compartment in the tips of growing root hairs, consistent with a role for the RHD4 protein in regulation of polarized membrane trafficking in these cells. The wild-type RHD4 gene was identified by map-based cloning and was found to encode a Sac1p-like phosphoinositide phosphatase. RHD4 displayed a preference for phosphatidylinositol-4-phosphate [PI(4)P] in vitro, and rhd4-1 roots accumulated higher levels of PI(4)P in vivo. In wild-type root hairs, PI(4)P accumulated primarily in a tip-localized plasma membrane domain, but in rhd4-1 mutants, significant levels of PI(4)P were detected associated with internal membranes. A fluorescent RHD4 fusion protein localized to membranes at the tips of growing root hairs. We propose that RHD4 is selectively recruited to RabA4b-labeled membranes that are involved in polarized expansion of root hair cells and that, in conjunction with the phosphoinositide kinase PI-4Kβ1, RHD4 regulates the accumulation of PI(4)P on membrane compartments at the tips of growing root hairs. [ABSTRACT FROM AUTHOR]

In vehicle-to-vehicle (V2V) communications, achieving reliable physical layer performance is a challenging task due to the highly dynamic nature of V2V propagation channels. Frame timing estimation, as one of the most critical signal processing procedures that rely on channel statistics, has to be appropriately enhanced to tackle this challenge. This study presents a novel frame timing estimation scheme based on both the available periodical preambles in IEEE 802.11p standard. By designing the fourth-order statistics-based correlation and differential normalisation functions, the proposed timing metric not only is capable of possessing an extensible correlation length, but also achieves the robustness to multipath effect and large carrier frequency offset. From the standpoints of hypothesis testing and classification, the proposed approach can effectively increase the distinction between correct and wrong timing indexes in terms of the class-separability criteria, and consequently has a significantly improved timing estimation performance compared with the existing methods. Simulation results consist with theoretical analysis under the typical V2V channel model, and demonstrate that the proposed method can significantly reduce both the probabilities of false alarm and missed detection, and make the selection of a suitable threshold for frame detection much easier. [ABSTRACT FROM AUTHOR]