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Background: Vascular dementia is the second common cause of dementia, only second to Alzheimer's disease in later life, and has a greater mortality risk than Alzheimer's disease among the elderly population group. The angiotensin-converting enzyme insertion/deletion polymorphism as a risk factor in vascular dementia has been suggested, but direct evidence from genetic association studies remain inconclusive.We performed ametaanalysis pooling data from all relevant studies in order to determine the effect of the insertion/deletion polymorphism on the vascular dementia. Methods: We applied a random-effects model or fixed-effects model to combine odds ratio and 95% confidence intervals. Q statistic was used to evaluate the homogeneity, and Egger's test and Funnel plot were used to assess publication bias. Results: A total of 10 studies were included worldwide. Publication bias was not observed. There was no evidence of the association of angiotensinconverting enzyme insertion/deletion polymorphism with the vascular dementia in general or in the Asian populations or in the Caucasian populations. Conclusions: The angiotensin-converting enzyme insertion/deletion polymorphism might be neutral to vascular dementia. [ABSTRACT FROM AUTHOR]

During three-roll planetary rolling, the microstructure of copper tube with initial columnar grains develops into an equiaxed grain structure due to the large rolling deformation and high rolling temperature. The microstructure of copper tubes significantly influences formability and properties due to the three-roll planetary rolling operation. It is very important to understand the microstructural evolution for such special processing. It was found that dynamic recrystallization occurred at the concentrating deformation zone, followed by rapid grain expansion that gradually stabilized. Corresponding with the transformation of microstructure, the hardness of the tube billet reduced gradually away from the roller's concentrating deformation zone. The changing of roller velocity is responsible for the extreme evolution of the microstructure in the concentrating deformation zone. Therefore, the properties of copper tubes can be controlled by concentrating the deformation zone. This research can facilitate the application of planetary rolling to the manufacture of tubes for low formability materials. [ABSTRACT FROM AUTHOR]

Our previous studies showed that cysteinyl leukotriene receptor-1 (CysLT1) antagonist pranlukast has a neuroprotective effect on cerebral ischemia in rats and mice. However, whether the neuroprotective effect of pranlukast is its special action or a common action of CysLT1 receptor antagonists remains to be clarified. This study was performed to determine whether montelukast, another CysLT1 receptor antagonist, has the neuroprotective effect on focal cerebral ischemia in mice, and to observe its dose- and time-dependent properties. Permanent focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO). Montelukast was injected intraperitoneally either as multiple doses (once a day for 3 days and 30 min before MCAO) or as a single dose (at 30 min before, 30 min after, or 1 h after MCAO), respectively, and pranlukast and edaravone were used as controls. The neurological deficits, infarct volumes, brain edema, neuron density, and Evans blue extravasation in the brain were determined 24 h after MCAO. Pretreatments with multiple doses or a single dose of montelukast (0.1 and 1.0 mg/kg) before MCAO significantly attenuated all the ischemic insults. Post-treatment with a single dose of montelukast (0.1 and 1.0 mg/kg) at 30 min after MCAO also significantly decreased brain edema and infarct volume, but not neurological deficits. However, post-treatment with a single dose of montelukast at 1 h after MCAO had no significant effect. Pranlukast showed the same effects as montelukast, but edaravone attenuated the ischemic insults only with multiple doses before MCAO. Thus, montelukast has a dose- and time-dependent neuroprotective effect on permanent focal cerebral ischemia in mice, with an effective dose range of 0.1–1.0 mg/kg and a therapeutic window of 30 min. These findings further support the therapeutic potential of CysLT1 receptor antagonists in the treatment of cerebral ischemia at earlier phases. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Although the secondary somatosensory cortex (SII) is known to be involved in pain perception, its role in pain modulation and neuropathic pain is yet unknown. In this study, we found that glutamatergic neurons in deep layers of the SII (SIIGlu) responded to bilateral sensory inputs by changing their firing with most being inhibited by contralateral noxious stimulation. Optical inhibition and activation of unilateral SIIGlu reduced and enhanced bilateral nociceptive sensitivity, respectively, without affecting mood status. Tracing experiments revealed that SIIGlu sent dense monosynaptic projections to the posterolateral nucleus (VPL) and the posterior nucleus (Po) of the thalamus. Optical inhibition and activation of projection terminals of SIIGlu in the unilateral VPL and Po inhibited and facilitated pain on the contralateral side, respectively. After partial sciatic nerve ligation, SIIGlu became hyperactive as evidenced by higher frequency of spontaneous firing, but the response patterns to peripheral stimulation remained. Optical inhibition of SIIGlu alleviated not only bilateral mechanical allodynia and thermal hyperalgesia but also the negative affect associated with spontaneous pain. Inhibition of SIIGlu terminals in the VPL and Po also relieved neuropathic pain. This study revealed that SIIGlu and the circuits to the VPL and Po constitute a part of the endogenous pain modulatory network. These corticothalamic circuits became hyperactive after peripheral nerve injury, hence contributes to neuropathic pain. These results justify proper inhibition of SIIGlu and associated neural circuits as a potential clinical strategy for neuropathic pain treatment. [ABSTRACT FROM AUTHOR]

Dihydroxynapthalene-(DHN) and L-dihydroxyphenylalanine (L-DOPA) are two types of dominant melanin in fungi. Fungal melanins with versatile functions are frequently associated with pathogenicity and stress tolerance. In rice blast fungus, Magnaporthe oryzae, DHN melanin is essential to maintain the integrity of the infectious structure, appressoria; but the role of the tyrosinase-derived L-DOPA melanin is still unknown. Here, we have genetically and biologically characterized a tyrosinase gene (MoTyr) in M. oryzae. MoTyr encodes a protein of 719 amino acids that contains the typical CuA and CuB domains of tyrosinase. The deletion mutant of MoTyr (DMoTyr) was obtained by using a homologous recombination approach. Phenotypic analysis showed that conidiophore stalks and conidia formation was significantly reduced in DMoTyr. Under different concentrations of glycerol and PEG, more appressoria collapsed in the mutant strains than in the wild type, suggesting MoTyr is associated with the integrity of the appressorium wall. Melanin measurement confirmed that MoTyr loss resulted in a significant decrease in melanin synthesis. Accordingly, the loss of MoTyr stunted the conidia germination under stress conditions. Importantly, the MoTyr deletion affected both infection and pathogenesis stages. These results suggest that MoTyr, like DHN pigment synthase, plays a key role in conidiophore stalks formation, appressorium integrity, and pathogenesis of M. oryzae, revealing a potential drug target for blast disease control. [ABSTRACT FROM AUTHOR]

Aspartate family includes five additional amino acids other than aspartate, among which most except aspartate have been reported for their action in pathogenesis by amino acid biosynthesis. However, how aspartate, the initial substrate of this family metabolic pathway, is involved in pathogenesis remains unknown. Here, we focused on aspartate transaminase (AST) that catalyzes transamination reaction between glutamate-aspartate in Magnaporthe oryzae. Three MoAST genes were bioinformatically analyzed, of which MoAST2 was uniquely upregulated when invasive hyphae switched to necrotrophic pathogenesis. MoAST2 deletion (ΔMoast2) caused a drastic reduction in conidiogenesis and appressorium formation. Particularly, ΔMoast2 was observed to be proliferated at the biotrophic phase but inhibited at the necrotrophic stage, and with invisible symptoms detected, suggesting a critical role in necrotrophic phase. Glutamate family restored the ΔMoast2 defects but aspartate family did not, inferring that transamination occurs from aspartate to glutamine. MoAST2 is cytosolic and possessed H2O2 stress tolerance. In parallel, Colletotrichum graminicola AST2, CgAST2 was proven to be a player in necrotrophic anthracnose development. Therefore, conserved AST2 is qualified to be a drug target for disease control.

Bicarbonate (HCO3-) transporter family including the anion exchanger (AE) group is involved in multiple physiological processes through regulating acid-base homeostasis. HCO3- transporters have been extensively studied in mammals, but fungal homologues of AE are poorly understood. Here, we characterized the AE group member (MoAE4) in Magnaporthe oryzae. MoAE4 exhibits more sequence and structure homologies with the reported AE4 and BOR1 proteins. In addition to the common sublocalization on cytomembrane, MoAE4 also localizes on tonoplast. Yeast complementation verified that MoAE4 rescues boron sensitivity and endows NaHCO3 tolerance in the BOR1 deleted yeast. MoAE4 gene is bicarbonate induced in M. oryzae; and loss of MoAE4 (ΔMoAE4) resulted in mycelial growth inhibited by NaHCO3. Lucigenin fluorescence quenching assay confirmed that ΔMoAE4 accumulated less HCO3 - in vacuole and more HCO3- in cytosol, revealing a real role of MoAE4 in bicarbonate transport. DMoAE4 was defective in conidiation, appressorium formation, and pathogenicity. More H2O2 was detected to be accumulated in ΔMoAE4 mycelia and infected rice cells. Summarily, our data delineate a cytomembrane and tonoplast located HCO3-transporter, which is required for development and pathogenicity in M. oryzae, and revealing a potential drug target for blast disease control. [ABSTRACT FROM AUTHOR]

Abstract Background Ubinuclein-2 (UBN2) is a nuclear protein that interacts with many transcription factors. The molecular role and mechanism of UBN2 in the development and progression of cancers, including colorectal cancer (CRC), is not well understood. The current study explored the role of UBN2 in the development and progression CRC. Methods Oncomine network and The Cancer Genome Atlas (TCGA) database were downloaded and Gene Set Enrichment Analysis (GSEA) was performed to compare the UBN2′s expression between normal and tumor tissues, as well as the potential correlation of UBN2 expression with signaling pathways. Immunohistochemistry (IHC), qRT-PCR and Western blotting were performed to determine the expression of UBN2 in CRC tissues or cell lines. In vitro proliferation and invasion assays, and orthotopic mouse metastatic model were used to analyze the effect of UBN2 on the development and progression of CRC. Results The analysis of UBN2 expression using Oncomine network showed that UBN2 was upregulated in CRC tissues compared to matched adjacent normal intestinal epithelial tissues. IHC, qRT-PCR and Western blotting confirmed that UBN2 expression is higher in CRC tissues compared with matched adjacent normal intestinal epithelial tissues. In addition, analyses of TCGA data revealed that high UBN2 expression was associated with advanced stages of lymph node metastasis, distant metastasis, and short survival time in CRC patients. IHC showed that high UBN2 expression is correlated with advanced stages of CRC. Moreover, UBN2 is highly expressed in the liver metastatic lesions. Furthermore, knockdown of UBN2 inhibited the growth, invasiveness and metastasis of CRC cells via regulation of the Ras/MAPK signaling pathway. Conclusion The current study demonstrates that UBN2 promotes tumor progression in CRC. UBN2 may be used as a promising biomarker for predicting the prognosis of CRC patients.

Primary inoculum that survives overwintering is one of the key factors that determine the outbreak of plant disease. Pathogenic resting structures, such as chlamydospores, are an ideal inoculum for plant disease. Puzzlingly, Magnaporthe oryzae, a devastating fungal pathogen responsible for blast disease in rice, hardly form any morphologically changed resting structures, and we hypothesize that M. oryzae mainly relies on its physiological alteration to survive overwintering or other harsh environments. However, little progress on research into regulatory genes that facilitate the overwintering of rice blast pathogens has been made so far. Serine threonine protein kinase AGC/AKT, MoSch9, plays an important role in the spore-mediated pathogenesis of M. oryzae. Building on this finding, we discovered that in genetic and biological terms, MoSch9 plays a critical role in conidiophore stalk formation, hyphal-mediated pathogenesis, cold stress tolerance, and overwintering survival of M. oryzae. We discovered that the formation of conidiophore stalks and disease propagation using spores was severely compromised in the mutant strains, whereas hyphal-mediated pathogenesis and the root infection capability of M. oryzae were completely eradicated due to MoSch9 deleted mutants’ inability to form an appressorium-like structure. Most importantly, the functional and transcriptomic study of wild-type and MoSch9 mutant strains showed that MoSch9 plays a regulatory role in cold stress tolerance of M. oryzae through the transcription regulation of secondary metabolite synthesis, ATP hydrolyzing, and cell wall integrity proteins during osmotic stress and cold temperatures. From these results, we conclude that MoSch9 is essential for fungal infection-related morphogenesis and overwintering of M. oryzae.

Aquaglyceroporins (GlpFs) that transport glycerol along with water and other uncharged solutes are involved in osmoregulation in myriad species. Fungal species form a large group of eukaryotic organisms, and their GlpFs may be diverse, exhibiting various activities. However, few filamentous fungal GlpFs have been biologically investigated. Here, a glpF gene from the halophilic fungus Aspergillus glaucus (AgglpF) was verified to be a channel of water or glycerol in Xenopus laevis oocytes and was further functionally analyzed in three heterologous systems. In Saccharomyces cerevisiae, cells overexpressing AgglpF possessed significant tolerance of drought, salt, and certain metal ions. AgglpF was then characterized in the filamentous fungus of Neurospora crassa. Based on the N. crassa aquaporin gene (NcAQP) disruption mutant (the Δaqp mutant), a series of complementary strains carrying NcAQP and AgglpF and three asparagine-proline-alanine-gene (NPA)-deleted AgglpF fragments were created. As revealed by salt resistance analysis, the AgglpF complementary strain possessed the highest salt resistance among the tested strains. In addition, the intracellular glycerol content in the AgglpF complementary strain was markedly higher than that in the other strains. The AgGlpF-green fluorescent protein (GFP) fusion protein was subcellularly localized in the plasma membrane of onion epidermal cells, suggesting that AgglpF functions in plants. Indeed, when AgglpF was expressed in Arabidopsis thaliana, transgenic lines survived under conditions of high osmotic stress and under conditions of drought stress in particular. Overall, our results revealed that AgGlpF as a water/glycerol transporter is required for survival of both fungi and plants under conditions of high osmotic stress and may have value in applications in genetic engineering for generating high salt and drought resistance. [ABSTRACT FROM AUTHOR]

BACKGROUNDThe flotillin family member flotillin-1 (FLOT1) encodes a caveolae-associated, integral membrane protein that belongs to lipid raft family and involves in vesicular trafficking and signal transduction. However, the role of FLOT1 in development and progression of cancer remains largely unknown. The present study was aimed to investigate the clinical and prognostic significance of FLOT1 in hepatocellular carcinoma (HCC).METHODSReal-time PCR and western blot analyses were applied to examine FLOT1 expression in fourteen HCC cell lines and one normal hepatic cell line, ten pairs of primary HCC and matched adjacent noncancerous liver tissues from the same patient. Immunohistochemistry (IHC) was performed to examine FLOT1 protein expression in paraffin-embedded tissues from 196 HCC patients. Statistical analyses were applied to evaluate the diagnostic value and associations of FLOT1 expression with clinical parameters.RESULTSFLOT1 expression was evidently up-regulated in HCC tissues compared with that in the matched adjacent noncancerous liver tissues. In the 196 cases of tested HCC samples, FLOT1 protein level was positively correlated with Tumor size (P = 0.025), clinical stage (PCONCLUSIONSOur study demonstrated FLOT1 is associated with aggressive characteristics of HCC, and suggested the possibility of its use as a prognostic marker in patients with HCC.

The mechanical properties of GH4169 alloy sheet after cold rolling (at 0%, 10%, 30%, 50% and 70%) and solid solution were investigated. The textures and Taylor factors were characterized using electron backscattering diffraction (EBSD). The fractions of δ phase were measured by X-ray diffraction. The contributions of δ phase, grain size, texture, and work hardening on the mechanical properties were also discussed. The results showed increases in the yield strength (YS) (0.2%) as well as the ultimate tensile strength (UTS) of GH4169 superalloy sheet after cold rolling, when rolling reduction was increased. In contrast, following solid solution treatment, YS and UTS were increased then subsequently decreased. The changes of yield strength of GH4169 superalloy were attributed to the texture and work hardening, followed by the grain refinement and precipitation of δ phase. When the rolling reduction was below 30%, the influence of δ phase was greater than grain refinement and when the rolling reduction was larger than 50%, the controversial results occur. The precipitation of δ phase promoted the improvement of yield strength, the relationship between the fraction of δ phase and improved yield strength satisfactory fit to the following equation: σδ = 15.9Wδ + 59.7.

Objective: To study the signs of subclavian artery angiography for hemoptysis due to pulmonary tuberculosis and to evaluate its clinical use in artery embolization., Methods: Thirty-nine patients with hemoptysis due to pulmonary tuberculosis underwent subclavian artery angiography after artery embolization performed in the hemorrhagic branches of descending aorta. Of the 39 cases, 25 had severe pulmonary fibrosis or were complicated with cavity formation, aspergilloma, pleural thickening and postoperative thorax. The signs of subclavian artery angiography were divided into three categories: (-), normal; (+), the branches of subclavian artery and axillary artery chaotic and hyperplasia; (+ +), the branches of subclavian artery and axillary artery appeared tortuosity, dilatation, aneurysm and shunt with pulmonary circulation. Signs of bleeding was designated (+) and (+ +), with (+ +) indicating strongly positive. The signs of subclavian artery angiography were studied and statistically analyzed. Artery embolization was performed in some of the patients, among whom 15 were analyzed for long-term clinical curative effect., Results: Signs of positive bleeding was found in 32/39 of the cases, and strongly positive bleeding in 17/39 of the cases. Positive bleeding arteries accounted for 39/58 of the branches, including 24/58 (+ +) and 15/58 (+). Angiography demonstrated that the internal mammary artery, lateral thoracic artery and subscapular artery were the main hemorrhagic arteries. Patients with severe pulmonary fibrosis or complicated with cavity, aspergilloma, pleural thickening and postoperative thorax showed higher rate of positive and strongly positive bleeding. Artery embolization was performed in 15 cases: cure was achieved in 6, effective in 7 and failure in 2 cases. Of the 15 cases, 8 had been ineffective after embolization of the hemorrhagic branches of descending aorta alone., Conclusions: Our results suggest that corresponding subclavian artery angiography should be performed after the hemorrhagic branches of descending aorta artery have been embolized for hemoptysis due to pulmonary tuberculosis, especially in cases with failed embolization, or complicated with severe pulmonary fibrosis, cavity formation, aspergilloma, pleural thickening, or postoperative thorax. The hemorrhagic arteries shown by subclavian artery angiography must be embolized.