5-Lipoxygenase (5-LOX) inhibitors have been shown to be protective in several neurodegenerative disease models; however, the underlying mechanisms remain unclear. We investigated whether 5-LOX inhibitor zileuton conferred direct neuroprotection against glutamate oxidative toxicity by inhibiting ferroptosis, a newly identified iron-dependent programmed cell death. Treatment of HT22 mouse neuronal cell line with glutamate resulted in significant cell death, which was inhibited by zileuton in a dose-dependent manner. Consistently, zileuton decreased glutamate-induced production of reactive oxygen species but did not restore glutamate-induced depletion of glutathione. Moreover, the pan-caspase inhibitor Z-Val-Ala-Asp(OMe)-fluoromethyl ketone (ZVAD-fmk) neither prevented HT22 cell death induced by glutamate nor affected zileuton protection against glutamate oxidative toxicity, suggesting that zileuton did not confer neuroprotection by inhibiting caspase-dependent apoptosis. Interestingly, glutamate-induced HT22 cell death was significantly inhibited by the ferroptosis inhibitor ferrostatin-1. Moreover, zileuton protected HT22 neuronal cells from erastin-induced ferroptosis. However, we did not observe synergic protective effects of zileuton and ferrostatin-1 on glutamate-induced cell death. These results suggested that both the 5-LOX inhibitor zileuton and the ferropotosis inhibitor ferrostatin-1 acted through the same cascade to protect against glutamate oxidative toxicity. In conclusion, our results suggested that zileuton protected neurons from glutamate-induced oxidative stress at least in part by inhibiting ferroptosis.
Five flavonoids (catechin, hyperoside, quercitrin, quercetin, and rutin) were separated and determined by capillary electrophoresis with electrochemical detection. Effects of several important factors, such as the pH and concentration of running buffer, separation voltage, injection time, and detection potential were investigated to determine the optimum conditions. The five flavonoids were baseline separated within 20 min in a 60 cm length capillary at a separation voltage of 19.5 kV with a running buffer consisting of 60 mmoL/L Na2B4O7 - 120 mmoL/L NaH2PO4 (pH = 8.8). The relationship between peak current and analyte concentration was linear over about two orders of magnitude with detection limits (S/N = 3) ranging from 0.02 to 0.05 microg/mL for all compounds. This method was successfully used to determine the above five flavonoids in Agrimonia pilosa Ledeb. with relatively simple extraction procedures, and the assay results were satisfactory.
Multiple players are involved in the highly complex pathophysiologic responses after stroke. Therefore, therapeutic approaches that target multiple cellular elements of the neurovascular unit in the damage cascade hold considerable promise for the treatment of stroke. Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to biologically active eicosanoids called epoxyeicosatrienoic acids (EETs), which are further converted by soluble epoxide hydrolase (sEH) to less bioactive diols. EETs have been shown to exert direct cytoprotective effects upon several individual components of the neurovascular unit under simulated ischemic conditions in vitro. However, the cellular mechanism underlying EET-mediated neuroprotective effects after ischemia remains to be clarified. In this study, we investigated the effects of 14,15-EET and 12-(3-adamantan-1-yl-ureido)dodecanoic acid (AUDA), a selective inhibitor of sEH, on multiple elements of neurovascular unit of the rat brain after middle cerebral artery occlusion-induced focal ischemia. The results showed that exogenous administration of 14,15-EET or AUDA could suppress astrogliosis and glial scar formation, inhibit microglia activation and inflammatory response, promote angiogenesis, attenuate neuronal apoptosis and infarct volume, and further promote the behavioral function recovery after focal ischemia. The results suggest that epoxyeicosanoid signaling is a promising multi-mechanism therapeutic target for the treatment of stroke.
The generation of reactive oxygen species (ROS) contributes to reperfusion-induced arrhythmias. In the present study, the antiarrhythmic effects of tempol and tiron, two membrane-permeable radical scavengers, on reperfusion-induced arrhythmias in rats in vivo were investigated. The anaesthetized rats were subjected to 5 min of left descending coronary artery (LAD) occlusion followed by 30 min of reperfusion. All rats pretreated with saline developed ventricular tachycardia (VT) and ventricular fibrillation (VF) at the onset of reperfusion, and most of the rats died from irreversible VF at the end of reperfusion. However, pretreatment with tempol (30 or 100 mg kg(-1)) 5 min before reperfusion reduced mortality, arrhythmia score and the incidence and duration of VT and VF. In the rats pretreated with high dose of tempol (100 mg kg(-1)), no VF happened and all rats were alive at the end of the experiment. The arrhythmia score was also significantly decreased compared with that of rats pretreated with saline (0.80 +/- 0.4 versus 5.6 +/- 0.4, P < 0.01). Tiron also provided nearly complete protection against reperfusion-induced arrhythmias when given 2 min before reperfusion. On the other hand, intravenous administration of tempol induced decreases in mean arterial pressure (MAP), heart rate (HR) and pressure rate index (PRI), a relative indicator of myocardial oxygen consumption. In order to determine whether the antiarrhythmic effects of tempol were secondary to the reduction of myocardial oxygen consumption, continuous electrical stimulation of the aortic depressor nerve (3 V, 10 ms and 10 Hz) was carried out in a group of rats to induce decreases in MAP, HR and PRI similar to those in the high dose of Tempol group. However, these rats did not show significant changes in the severity of reperfusion-induced arrhythmias. We conclude that both tempol and tiron significantly reduce reperfusion-induced arrhythmias in rats, and this protective action is independent of hemodynamic effects.
Chaperonin-mediated protein folding is complex. There have been diverse results on folding behavior, and the chaperonin molecules have been investigated as enhancing or retarding the folding rate. To understand the diversity of chaperonin-mediated protein folding, we report a study based on simulations using a simplified Gō-type model. By considering effects of affinity between the substrate protein and the chaperonin wall and spatial confinement of the chaperonin cavity, we study the thermodynamics and kinetics of folding of an unfrustrated substrate protein encapsulated in a chaperonin cavity. The affinity makes the hydrophobic residues of the protein bind to the chaperonin wall, and a strong (or weak) affinity results in a large (or small) effect of binding. Compared with the folding in bulk, the folding in chaperonin cavity with different strengths of affinity shows two kinds of behaviors: one with less dependence on the affinity but more reliance on the spatial confinement effect and the other relying strongly on the affinity. It is found that the enhancement or retardation of the folding rate depends on the competition between the spatial confinement and the affinity due to the chaperonin cavity, and a strong affinity produces a slow folding while a weak affinity induces a fast folding. The crossover between two kinds of folding behaviors happens in the case that the favorable effect of confinement is balanced by the unfavorable effect of the affinity, and a critical affinity strength is roughly defined. By analyzing the contacts formed between the residues of the protein and the chaperonin wall and between the residues of the protein themselves, the role of the affinity in the folding processes is studied. The binding of the residues with the chaperonin wall reduces the formation of both native contacts and nonnative contact or mis-contacts, providing a loose structure for further folding after allosteric change of the chaperonin cavity. In addition, 15 single-site-mutated mutants are simulated in order to test the validity of our model and to investigate the importance of affinity. Inspiringly, our results of the folding rates have a good correlation with those obtained from experiments. The folding rates are inversely correlated with the strength of the binding interactions, i.e., the weaker the binding, the faster the folding. We also find that the inner hydrophobic residues have larger effects on the folding kinetics than those of the exterior hydrophobic residues. We suggest that, besides the confinement effect, the affinity acts as another important factor to affect the folding of the substrate proteins in chaperonin systems, providing an understanding of the folding mechanism of the molecular chaperonin systems.
Labeling proteins with biotin is a widely used method to identify target proteins due to biotin's strong binding affinity for streptavidin. Combined with alkyne-azide cycloaddition, which enables the coupling of probes to targeted proteins, biotin tags linked to an alkyne or azide have become a powerful tool for purification and analysis of proteins in proteomics. However, biotin requires harsh elution conditions to release the captured protein from the bead matrix. Use of these conditions reduces signal to noise and complicates the analysis. To improve affinity capture, cleavable linkers have been introduced. Here, we demonstrate the use of a cyclic acetal biotin probe that is prepared easily from commercially available starting materials, is stable to cell lysates, yet is cleaved under mildly acidic conditions, and which provides an aldehyde for further elaboration of the protein, if desired.
In this study, single and double-labeling immunofluorescence histochemistry, Western blot and real-time polymerase chain reaction were used to study the expression of P2Y(6) receptors in developing mouse skeletal muscle and during injury and repair. The results show that P2Y(6) receptor immunoreactive (ir) cells were first detected in the dermamyotome at embryonic (E) day 9. The number and immunostaining intensity of the P2Y(6) receptor-ir cells increased from E9 to E13, but decreased from E15 to postnatal day 60 in the developing skeletal muscle system. The expression levels of P2Y(6) receptor protein and mRNA increased rapidly from 1 to 5 days after skeletal muscle injury and then decreased almost to the control level from 7 to 10 days, at the beginning of regeneration. P2Y(6) receptor-immunoreactivity was mainly localized to the ends of single myoblasts and myotube processes in the developing and injury-repair skeletal muscle tissues. These data suggest that the P2Y(6) receptor may be involved in the development and regeneration of skeletal muscle, especially in the migration and extension of the myoblast and myotube in developing and regenerating skeletal muscle.
In recent years, haze pollution in China is becoming increasingly serious, especially in the Beijing-Tianjin-Hebei region. In order to identify the temporal and spatial distributional characteristics of PM2.5 aerosol mass concentration in the region, this study selected the inland plain of the Beijing-Tianjin-Hebei region as the research area, and used MODIS AOD as the main predictor in a mixed effects model to establish the daily relationship of AOD-PM2.5 in the study area, from 2013 to 2014. The model was validated by a ten-fold cross validation method. The results showed that the correlation between AOD-PM2.5 can be improved by daily calibration of the mixed effects model (R2=0.78); the cross-validated R2 was 0.70, and RMSE and RPE were 20.80 μg·m-3 and 28.76%, respectively. Considering the importance of unbiased PM2.5 predictions, the correction factors calculated from the surface PM2.5 measurements were applied to correct the biases in the predicted annual average PM2.5 concentrations introduced by non-stochastic missing AOD measurements. The results showed that the annual average concentration of PM2.5 in the study area was higher than 75 μg·m-3, and the spatial distribution of PM2.5 concentration was higher in the southern and western regions, and lower in the northern and eastern regions. These results suggest that the mixed effects model can be used to monitor ground PM2.5, and also provide a scientific basis for the control of atmospheric particulate pollution in the region.
Primary pulmonary epithelioid angiosarcoma is an extremely rare malignancy. Herein, we report the case of an elderly Chinese patient with primary pulmonary epithelioid angiosarcoma. The 72-year-old man presented with a 1-month history of persistent hemoptysis and left chest pain and weight loss of 3 kg. A chest computed tomography (CT) scan revealed two masses (maximum size 3.0 cm × 2.0 cm and 0.8 cm × 0.5 cm) in right lower lobe. We performed a left thoracotomy for tumor resection. Pathological examination showed that there was a significant amount of hemorrhage, fibrinous exudates, degeneration, and necrosis. With immunohistochemical analysis, tumor cells had strong expression of CD34, FLI-1, vimentin. Morphological and immunohistochemical findings supported the diagnosis of epithelioid angiosarcoma.
As an important form of agricultural non-point source pollution, soil nitrogen leaching deteriorates water quality. Compared with non-mulching cultivated land, field experiment explored the change characteristics of soil nitrogen leaching under plastic film mulching ridge-furrow in Wulongchi small watershed during summer maize growing period. The results showed that the amounts of mulching tillage soil TN and NO3--N leaching were significantly lower than those with non-mulched treatment, by 25.68% and 20.25%, respectively. With the advance of the summer maize growth period, leaching amount of mulched soil TN was highest at seedling stage, lowest at heading stage and higher in maturation period; leaching amount of mulched soil NO3--N was highest at seedling stage, lowest in maturation period; leaching amount of mulched soil NH4+-N was lower at seedling stage, increased to the peak at the jointing stage, decreased to the valley value at heading stage, and obviously increased in maturation period. Linear function relationship was found between mulched soil TN leaching and TN content, while exponential relationship was found between mulched soil NO3--N leaching and NO3--N content. In addition, there was linear function relationship of mulched soil TN and NO3--N leaching amount with soil moisture and rainfall. It was concluded that the plastic film mulched on summer maize could reduce the leaching loss of soil nitrogen, and it would have a significant effect on the reduction of reservoir area of agricultural non-point source pollution.
To quantify the ratio of CH4 ebullition to total flux in subtropical shallow ponds, the CH4 flux at the water-air interface was measured using the inverted-funnel and water equilibrium methods in two small ponds in Quanjiao, Anhui Province from July 28 to August 13, 2016. The average CH4 ebullition fluxes were 121.78 and 161.08 mg·(m2·d)-1 and the average diffusion fluxes were 3.38 and 3.79 mg·(m2·d)-1 over pond A and pond B, respectively. The ebullition flux accounted for 97.5% and 96.4% of the total flux over pond A and pond B, respectively. Methane ebullition ranged from 0.11 to 446.90 mg·(m2·d)-1 over pond A and from 0.05 to 607.51 mg·(m2·d)-1 over pond B. Gas ebullition rate during the day was higher than that at night and was controlled by wind speed. Methane ebullition flux was influenced by wind speed over the shallow pond at hourly scale and by water depth and wind speed at daily scale, with positive correlation with wind speed and negative correlation with water depth. Varying with latitude, methane ebullition flux was higher for the water bodies in the mid-latitude region compared to those in the high-latitude region. Direct observations of the methane ebullition flux over small ponds provide data support and theoretical reference to precisely estimate the contribution of inland water bodies to regional and global carbon cycle.
We have previously shown increased cardiac stanniocalcin-1 (STC1) in patients with idiopathic dilated cardiomyopathy. STC1 localizes to the inner mitochondrial membrane and transgenic over-expression of STC1 is associated with increased energy utilization.
We examined the hypothesis that STC1 uncouples mitochondrial oxidative phosphorylation--to suppress superoxide generation and modulate neurohormonal effects on cardiomyocytes.
Compared to WT mouse heart, STC1 Tg heart displays: 2-fold higher uncoupling protein 3 (UCP3) levels, but no effect on UCP2 protein; 40% lower ATP levels; but similar activities of respiratory chain complexes I-IV. In cultured adult rat and freshly-isolated mouse cardiomyocytes, rSTC1 induces UCP3, but not UCP2. Treatment of cardiomyocytes with STC1 decreases mitochondrial membrane potential and suppresses baseline and angiotensin II (Ang II)-induced superoxide generation. Furthermore, baseline superoxide generation is higher in freshly-isolated adult UCP3(-/-) mouse cardiomyocytes compared to WT, suggesting an important role for UCP3 in regulating cardiomyocyte ROS under physiologic conditions. Treatment of UCP3(-/-) cardiomyocytes with rSTC1 failed to suppress superoxide generation, suggesting that the effects of STC1 on superoxide generation in cardiomyocytes are UCP3-dependent.
STC1 activates a novel anti-oxidant pathway in cardiac myocytes through induction of UCP3, and may play an important role in suppressing ROS in the heart under normal physiologic conditions and ameliorate the deleterious effects of Ang II-mediated cardiac injury. Importantly, our data point to a critical role for the mitochondria in regulating ROS generation in response to Ang II.
Boolean multiplex (multilevel) networks (BMNs) are currently receiving considerable attention as theoretical arguments for modeling of biological systems and system level analysis. Studying control-related problems in BMNs may not only provide new views into the intrinsic control in complex biological systems, but also enable us to develop a method for manipulating biological systems using exogenous inputs. In this article, the observability of the Boolean multiplex control networks (BMCNs) are studied. First, the dynamical model and structure of BMCNs with control inputs and outputs are constructed. By using of Semi-Tensor Product (STP) approach, the logical dynamics of BMCNs is converted into an equivalent algebraic representation. Then, the observability of the BMCNs with two different kinds of control inputs is investigated by giving necessary and sufficient conditions. Finally, examples are given to illustrate the efficiency of the obtained theoretical results.
Reduced imine cage (RCC3) was first adopted for the preparation of porous organic cage embedded C18 amide silica stationary phase for high performance liquid chromatography. The prepared stationary phase was characterized by scanning electron microscope (SEM) and Fourier transformation infrared spectrum (FT-IR). Its chromatographic performance under reversed-phase mode was investigated in detail and compared with that of an ODS column. Multiple interactions, including hydrophobic interaction, π-π interactions, electrostatic interactions and hydrogen bonding, were involved due to the synergism of the C18 chain and RCC3. The column showed typical methylene selectivity and enhanced aromatic selectivity for nonpolar analytes while demonstrating high selectivity for polar analytes. In addition, the stationary phase showed the capability of separation of polar and hydrophilic compounds under per aqueous liquid chromatography mode (PALC), providing a green and economical way for the separation of polar and hydrophilic compounds. These results indicated the great application potential of the prepared stationary phase in the analysis of complex samples.
It has been suggested that propofol can modulate microglial activity and hence may have potential roles against neuroinflammation following brain ischemic insult. However, whether and how propofol can inhibit post-cardiac arrest brain injury via inhibition of microglia activation remains unclear. A rat model of asphyxia cardiac arrest (CA) was created followed by cardiopulmonary resuscitation. CA induced marked microglial activation in the hippocampal CA1 region, revealed by increased OX42 and P2 class of purinoceptor 7 (P2X7R) expression, as well as p38 MAPK phosphorylation. Morris water maze showed that learning and memory deficits following CA could be inhibited or alleviated by pre-treatment with the microglial inhibitor minocycline or propofol. Microglial activation was significantly suppressed likely via the P2X7R/p-p38 pathway by propofol. Moreover, hippocampal neuronal injuries after CA were remarkably attenuated by propofol. In vitro experiment showed that propofol pre-treatment inhibited ATP-induced microglial activation and release of tumor necrosis factor-α and interleukin-1β. In addition, propofol protected neurons from injury when co-culturing with ATP-treated microglia. Our data suggest that propofol pre-treatment inhibits CA-induced microglial activation and neuronal injury in the hippocampus and ultimately improves cognitive function. We proposed a possible mechanism of propofol-mediated brain protection after cardiac arrest (CA). CA induces P2X7R upregulation and p38 phosphorylation in microglia, which induces release of TNF-α and IL-1β and consequent neuronal injury. Propofol could inhibit microglial activation and alleviate neuronal damage. Our results suggest propofol-induced anti-inflammatory treatment as a plausible strategy for therapeutic intervention in post-CA brain injury.
We explored the potential involvement of FoxO3a activation in erythroid and granulocytic differentiation for Ph(+) cells of chronic myeloid leukemia blast crisis (CML BC). We demonstrate that FoxO3a activation in CML blast crisis (BC) cells by overexpressing FoxO3a leads to the maturation of CML BC cells. Hemoglobin production significantly increased upon FoxO3a activation in CML BC cells. FoxO3a activation upregulated erythroid surface protein (glycophorin A, GPA), but did not significantly modulate granulocytic markers (CD11b). Additionally, FoxO3a activation reduced the mRNA and protein expression of Tal1. Similar results were observed in cells that were given nilotinib. Our results indicate that FoxO3a activation may promote erythroid differentiation of BC cells via down-regulating Tal1 expression.
A validated LC-MS/MS method to determine the content of dipfluzine (Dip) and its three metabolites (M1, M2, and M5) simultaneously within rat plasma samples was developed. After a single liquid-liquid extraction, the assay was performed by using a C18 column and positive electrospray ionisation mode (ESI) in the multiple reaction monitoring (MRM) mode with transitions of m/z 417.3→167.3, 251.2→165.2, 199.1→121.3, and 183.2→105.1 for Dip, M1, M2, and M5, respectively. Sulfamethoxazole (SMZ) was used as internal standard (IS). The method was linear ranged from 0.5-518, 0.5-524, 1.0-1036, and 0.5-514 ng/ml for Dip, M1, M2, and M5, respectively and all correlation coefficients were greater than 0.9919. The intra- and inter-day precision values obtained were less than 11.5% and the accuracy was between -3.2 and 9.7% for each analyte. The extraction recoveries of their three concentrations for Dip and its three metabolites were all higher than 71.9%. The technique was successfully applied to a pharmacokinetic study of Dip and its metabolites after a single oral administration of Dip (20 mg/kg) to rats. The results indicated that the metabolite formation was rapid and generated M5 as the predominant metabolite, followed by M1 and M2. The maximum plasma concentrations (Cmax) were 59±7, 37±4, 3±0.2, and 55±5 ng/ml; the time to maximum plasma concentration (Tmax) were 65±12, 95±12, 190±25, and 90±0 min and the areas under the concentration-time curves (AUC0→∞) were 17573±704, 8328±355, 5602±753, and 16101±429 ng min/ml for Dip, M1, M2, and M5, respectively. These results suggested that Dip was extensively metabolized and rapidly absorbed. The half-life (t1/2) of Dip, M1, M2, and M5 were 329±15, 767±75, 2364±434, and 378±36 min, respectively, which indicated that Dip and M5 were eliminated quickly. M2 reached its Tmax later and exhibited a longer t1/2 than the other metabolites, which indicated that there might be some type of flip-flop mechanism at work in the pharmacokinetics of M2.
The adulteration of animal feed as well as milk products with melamine has led to concerns about the ability to establish appropriate withdrawal intervals to ensure food safety. Two experiments were conducted in this study. The first was to investigate the deposition and depletion of melamine in blood and tissues of pigs exposed to adulterated feed with high doses of melamine. A total of 500 or 1000 mg kg(-1) melamine was added to the diet for fattening pigs (initial BW = ±60.24 kg). Melamine residues were detected in tissues (brain, duodenum, liver, heart, muscle and kidney) by LC-MS/MS. Dose-dependent effects were found between melamine residual concentration and its dose in feed. Five days after the withdrawal of melamine from the diets, the residue concentration in tissues fell below 2.5 mg kg(-1). In the second experiment, blood samples were taken at different time points from fattening pigs (BW = 100 kg) fed with adulterated feed with 1000 mg kg(-1) of melamine for 42 days. Results from the pharmacokinetics analysis showed that it would take 83 h for the melamine level in plasma depleting to the safe level of 50 ng ml(-1) after an expose of 1000 mg kg(-1) melamine contaminated feed for 42 days.
This paper focus on changes of high solid content sludge (7%, 9% and 13%) hydrolysis with microwave irradiation also anaerobic biodegradation of treated sludge was tested by biochemical methane potential (BMP) procedure. Results showed that microwave irradiation provided a rapid temperature increasing. Hydrolysis accelerated the solubilization of volatile suspended solid (VSS) and suspended solid (SS). COD, TOC, NH4+-N, TN, and TP concentration of liquor sludge increased, while pH decreased. Sludge solid content was found to be the most influential parameter. VSS and SS dissolving ratio of sludge with 13% solid content were lower than sludge with 7% and 9% solid content. 23% of VSS and 18% of SS dissolved for 9% sludge at 170 degrees C with 5 min, SCOD of liquor was 41 g/L, and concentration of TOC and NH4+-N were 30 g/L and 1 g/L respectively. Biodegradation of treated sludge improved. Methane production of 9% sludge at 170 degrees C with 5 min and 10 min were 27% and 30.8% higher than that of untreated sludge. Hydrolysis time increasing from 5 min to 10 min brought an improvement of 4%, 3.6% and 5.7% methane production at 120 degrees C, 150 degrees C and 170 degrees C.
Endocannabinoid (eCB) signaling is tightly regulated by eCB biosynthetic and degradative enzymes. The eCB 2-arachidonoylglycerol (2-AG) is hydrolyzed primarily by monoacylglycerol lipase (MAGL). Here, we investigated whether eCB signaling, synaptic function, and learning behavior were altered in MAGL knock-out mice. We report that MAGL⁻/⁻ mice exhibited prolonged depolarization-induced suppression of inhibition (DSI) in hippocampal CA1 pyramidal neurons, providing genetic evidence that the inactivation of 2-AG by MAGL determines the time course of the eCB-mediated retrograde synaptic depression. CB₁ receptor antagonists enhanced basal IPSCs in CA1 pyramidal neurons in MAGL⁻/⁻ mice, while the magnitude of DSI or CB₁ receptor agonist-induced depression of IPSCs was decreased in MAGL⁻/⁻ mice. These results suggest that 2-AG elevations in MAGL⁻/⁻ mice cause tonic activation and partial desensitization of CB₁ receptors. Genetic deletion of MAGL selectively enhanced theta burst stimulation (TBS)-induced long-term potentiation (LTP) in the CA1 region of hippocampal slices but had no significant effect on LTP induced by high-frequency stimulation or long-term depression induced by low-frequency stimulation. The enhancement of TBS-LTP in MAGL⁻/⁻ mice appears to be mediated by 2-AG-induced suppression of GABA(A) receptor-mediated inhibition. MAGL⁻/⁻ mice exhibited enhanced learning as shown by improved performance in novel object recognition and Morris water maze. These results indicate that genetic deletion of MAGL causes profound changes in eCB signaling, long-term synaptic plasticity, and learning behavior.
Image-based morphometry is an important area of pattern recognition research, with numerous applications in science and technology (including biology and medicine). Fisher Linear Discriminant Analysis (FLDA) techniques are often employed to elucidate and visualize important information that discriminates between two or more populations. We demonstrate that the direct application of FLDA can lead to undesirable errors in characterizing such information and that the reason for such errors is not necessarily the ill conditioning in the resulting generalized eigenvalue problem, as usually assumed. We show that the regularized eigenvalue decomposition often used is related to solving a modified FLDA criterion that includes a least-squares-type representation penalty, and derive the relationship explicitly. We demonstrate the concepts by applying this modified technique to several problems in image-based morphometry, and build discriminant representative models for different data sets.
The Arabidopsis thaliana tandem zinc finger 1 (AtTZF1) protein is characterized by two tandem-arrayed CCCH-type zinc fingers. We have previously found that AtTZF1 affects hormone-mediated growth, stress and gene expression responses. While much has been learned at the genetic and physiological level, the molecular mechanisms underlying the effects of AtTZF1 on gene expression remain obscure. A human TZF protein, hTTP, is known to bind and trigger the degradation of mRNAs containing AU-rich elements (AREs) at the 3' untranslated regions. However, while the TZF motif of hTTP is characterized by C(X8)C(X5)C(X3)H-(X18)-C(X8)C(X5)C(X3)H, AtTZF1 contains an atypical motif of C(X7)C(X5)C(X3)H-(X16)-C(X5)C(X4)C(X3)H. Moreover, the TZF motif of AtTZF1 is preceded by an arginine-rich (RR) region that is unique to plants. Using fluorescence anisotropy and electrophoretic mobility shift binding assays, we have demonstrated that AtTZF1 binds to RNA molecules with specificity and the interaction is dependent on the presence of zinc. Compared with hTTP, in which TZF is solely responsible for RNA binding, both TZF and RR regions of AtTZF1 are required to achieve high-affinity RNA binding. Moreover, zinc finger integrity is vital for RNA binding. Using a plant protoplast transient expression analysis we have further revealed that AtTZF1 can trigger the decay of ARE-containing mRNAs in vivo. Taken together, our results support the notion that AtTZF1 is involved in RNA turnover.
Interleukin 17A (IL-17A) is a critical cytokine involved in inflammatory diseases and inflammation-associated cancers. Increasing case-control studies have implicated crucial roles of IL-17A single nucleotide polymorphisms (G197A and C1249T) in gastric carcinogenesis, but providing inconclusive findings. The present study is aimed to estimate the association of IL-17A G197A and C1249T polymorphisms with gastric cancer risk by pooling all available publications. A comprehensive literature search in PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases was performed for eligible publications from their inception up to May 5, 2014. The pooled odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were calculated to estimate the effect of IL-17A polymorphisms on gastric carcinogenesis. Stratified analysis by ethnicity, Helicobacter pylori (H. pylori) infection, and smoking status were also conducted. All analyses were performed by using the Stata 12.0 software. There were five case-control studies with 2,774 cases and 3,162 controls and two case-control studies with 620 cases and 1,123 controls on the susceptibility of IL-17A G197A and C1249T polymorphisms to gastric cancer, respectively. Significant association was observed between IL-17A G197A polymorphism and gastric cancer risk, particularly among Asians. The status of H. pylori infection and smoking did not influence this association. In addition, the IL-17A C1249T polymorphism did not confer a risk effect on gastric carcinogenesis. The pooled results were not materially altered by sensitivity analysis. We firstly show that the polymorphism of IL-17A G197A but not C1249T is a risk factor for gastric cancer.
Vascular calcification is currently recognized as an important pathobiological process in atherosclerosis, but the mechanism remains elusive. Given the similarities in vascular calcification and bone formation, 18F-sodium fluoride (18F-NaF) is now considered a novel marker of vascular calcification. This study aimed to correlate 18F-NaF accumulation with the histological characterization of vascular calcification in carotid plaques.
A total of 8 patients who were undergoing carotid endarterectomy (CEA) for carotid artery stenosis were recruited. Before CEA, 18F-NaF positron emission tomography and computed tomography (PET-CT) studies were conducted. 18F-NaF uptake was measured by the maximum standardized uptake value and the target-to-background ratio. The Hounsfield unit (HU) value was also measured. Postoperative carotid plaques were investigated by hematoxylin and eosin staining, alizarin red staining, and immunohistochemistry (alpha-smooth muscle actin and CD68).
18F-NaF uptake was observed in the bilateral carotid bifurcation of all patients. Compared with the pathology results, there was a significant correlation between tracer activity in the carotid plaques and the calcification in the corresponding histological sections (integrated optical density [IOD]: r = .781, P = .022; positive area: r = .765, P = .027). A negative correlation was observed between 18F-NaF uptake and smooth muscle cell staining (IOD: r = -.710, P = .049). 18F-NaF uptake did not correlate with carotid artery stenosis, HU value, or inflammation.
18F-NaF PET-CT is a noninvasive imaging method for the assessment of calcification in human carotid atherosclerotic plaques and a promising approach to studying calcification in atherosclerotic lesions.