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Abstract Thyroid gland vasculature has a distinguishable characteristic of endothelial fenestrae, a critical component for proper molecular transport. However, the signaling pathway that critically governs the maintenance of thyroid vascular integrity, including endothelial fenestrae, is poorly understood. Here, we found profound and distinct expression of follicular epithelial VEGF‐A and vascular VEGFR2 that were precisely regulated by circulating thyrotropin, while there were no meaningful expression of angiopoietin–Tie2 system in the thyroid gland. Our genetic depletion experiments revealed that VEGFR2, but not VEGFR3, is indispensable for maintenance of thyroid vascular integrity. Notably, blockade of VEGF‐A or VEGFR2 not only abrogated vascular remodeling but also inhibited follicular hypertrophy, which led to the reduction of thyroid weights during goitrogenesis. Importantly, VEGFR2 blockade alone was sufficient to cause a reduction of endothelial fenestrae with decreases in thyrotropin‐responsive genes in goitrogen‐fed thyroids. Collectively, these findings establish follicular VEGF‐A–vascular VEGFR2 axis as a main regulator for thyrotropin‐dependent thyroid angiofollicular remodeling and goitrogenesis.

Propagation of α-synuclein aggregates has been suggested as a contributing factor in Parkinson's disease (PD) progression. However, the molecular mechanisms underlying α- synuclein aggregation are not fully understood. Here, we demonstrate in cell culture, nematode, and rodent models of PD that leucine-rich repeat kinase 2 (LRRK2), a PD-linked kinase, modulates α-synuclein propagation in a kinase activity-dependent manner. The PD-linked G2019S mutation in LRRK2, which increases kinase activity, enhances propagation efficiency. Furthermore, we show that the role of LRRK2 in α-synuclein propagation is mediated by RAB35 phosphorylation. Constitutive activation of RAB35 overrides the reduced α-synuclein propagation phenotype in lrk-1 mutant C. elegans. Finally, in a mouse model of synucleinopathy, administration of an LRRK2 kinase inhibitor reduced α-synuclein aggregation via enhanced interaction of α-synuclein with the lysosomal degradation pathway. These results suggest that LRRK2-mediated RAB35 phosphorylation is a potential therapeutic target for modifying disease progression. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) contribute to the development of non-alcoholic fatty liver disease. ROS generation by infiltrating macrophages involves multiple mechanisms, including Toll-like receptor 4 (TLR4)-mediated NADPH oxidase (NOX) activation. Here, we show that palmitate-stimulated CD11b+F4/80low hepatic infiltrating macrophages, but not CD11b+F4/ 80high Kupffer cells, generate ROS via dynamin-mediated endocytosis of TLR4 and NOX2, independently from MyD88 and TRIF. We demonstrate that differently from LPS-mediated dimerization of the TLR4-MD2 complex, palmitate binds a monomeric TLR4-MD2 complex that triggers endocytosis, ROS generation and increases pro-interleukin-1β expression in macrophages. Palmitate-induced ROS generation in human CD68lowCD14high macrophages is strongly suppressed by inhibition of dynamin. Furthermore, Nox2-deficient mice are protected against high-fat diet-induced hepatic steatosis and insulin resistance. Therefore, endocytosis of TLR4 and NOX2 into macrophages might be a novel therapeutic target for non-alcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]

Background: Hematogeneous infectious spondylodiscitis usually occurs in older immunocompromised patients with other comorbidities. They are usually unable to undergo reconstructive anterior and posterior surgeries. Therefore, an alternative, less aggressive surgical method of transpedicular curettage and drainage was suggested. This study was designed to compare the surgical outcomes for the treatment of hematogeneous infectious spondylodiscitis between transpedicular curettage and drainage technique and conventional combined anterior and posterior surgery. Materials and Methods: Between January 2002 and July 2011, 26 patients underwent surgical treatment for hematogeneous infectious spondylodiscitis. The patients were classified into two groups depending on surgical modality: a transpedicular curettage and drainage (TCD) group and a combined anterior and posterior surgery (CAPS) group. Results: The TCD group consisted of 10 patients (mean age 68.0 years), and the CAPS group consisted of 16 patients (mean age 58.4 years).The mean postoperative followup periods were 36.9 (months) in the TCD group and 69.9 (months) in the CAPS group. The operation time was 180.6 ± 33.6 minutes in the TCD group and 332.7 ± 74.5 minutes in the CAPS group (P < 0.05). Postoperative independent ambulation began at postoperative 4.9 ± 2.4 days in the TCD group but at postoperative 15.1 ± 15.3 days in the CAPS group (P < 0.05). The postoperative hospital stays were 19.9 ± 7.8 days in the TCD group and 35.4 ± 33.3 days in the CAPS group (P < 0.05). The level of C-reactive proteins decreased significantly in both groups after surgery (P < 0.05). Conclusion: Transpedicular curettage and drainage technique proved to be a useful technique for treating hematogeneous infectious spondylodiscitis in patients who were in poor heath with multiple comorbidities unable to undergo the conventional combined anterior and posterior surgery in a single day in terms of earlier ambulation, shorter hospitalization and similar clinical success rate. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to evaluate of prevalence of coexisting spine and hip disease using initial screening kidney-ureter-bladder (KUB) radiograph in patients over 50 who underwent spinal surgery. Materials and Methods: The study subjects were 388 patients (male: female=117:271; mean age 62.0 years) who underwent spinal surgery between 2008 and 2010. We retrospectively reviewed the initial KUB radiographs used to diagnose the spine and hip disease. Depending on the extent of acetabular and hip joint visualization in KUB, we divided the subjects into three groups: Acetabulum, hip joint, and femoral neck visualization. The hip visualization rate was also assessed with respect to patient height. χ2 and logistic regression test were used for statistical analysis. Results: 126 (32.5%) cases had significant hip pathology including hip osteoarthritis (Kellgren/Lawrence grade 3 in 123 cases, grade 4 in 3 cases) and avascular necrosis (1 case each of Ficat stage IIA and IIB), and 8 cases had other morphologic abnormalities. Regarding Acetabulum-hip visualization in KUB, 7 (1.8%) cases had acetabulum visualization only, 16 (4.1%) had hip joint visualization, and 365 (94.1%) had femoral neck including lesser trochanter visualization. Patients were categorized into four groups according to height (less than 150 cm, 150-159 cm, 160-169 cm, greater than 170 cm). The hip visualization rates differed significantly among these four groups (P<0.05). Conclusions: The prevalence of discernible hip pathology in patients who underwent spinal surgery was 32.5%. Hip joint visualization was excellent (98.2%) in KUB radiographs. Hence, spinal surgeons should pay attention to hip pathology in surgically indicated spinal patients. [ABSTRACT FROM AUTHOR]

Background: The osteoporosis and lumbar canal stenosis, in elderly patients are under diagnosed and under reported. We report a cross sectional study to demonstrate the osteoporotic profile in patients with lumbar spinal stenosis (LSS) and to determine the proportion of patients with LSS who need to be treated for osteoporosis. Materials and Methods: One hundred and six postmenopausal patients with symptomatic LSS were evaluated for osteoporotic profile, which included lumbar and hip bone mineral density (BMD), serum vitamin D concentration, bone resorption and formation markers. Demographic and disease related variables were analyzed to identify the association with the risk of osteoporosis or osteopenia. Statistical analysis used were multivariate logistic regression with a forward stepwise procedure. Results: Twenty-four patients (22.6%) had osteoporosis and 60 (56.6%) had osteopenia. Overall, 84 patients (79.2%) with symptomatic LSS had osteoporosis or osteopenia. Fifty-nine patients (55.6%) had hypovitaminosis D. All bone turnover makers [alkaline phosphatase, osteocalcin, urinary-N-terminal telopeptide (u-NTx)] were demonstrated to be within normal range. Only age was associated with the risk of osteoporosis or osteopenia in the hip region. In the lumbar spine, all variables were not associated with osteoporosis or osteopenia. 44 patients (41.5%) required treatment for osteoporosis as per risk factors for osteoporosis. According to the guidelines from the Health Insurance Review Agency, however, only 20 patients (18.8% required) qualified for reimbursement for osteoporosis medications. Conclusions: LSS is associated with osteopenia, osteoporosis, and hypovitaminosis D, which should prompt careful screening and treatment in cases of osteoporosis and osteoarthritis. [ABSTRACT FROM AUTHOR]

This study evaluates the otolith function of patients with head trauma, postulating that otolith dysfunction is a cause of nonspecific dizziness after head trauma. We prospectively enrolled 28 patients referred within 3 months after head trauma between March 2007 and December 2009. Pure tone audiometry, caloric testing and otolith function tests, including cervical vestibular evoked myogenic potential (cVEMP) and subjective visual vertical (SVV) tests, were performed on all patients. The relationship between otolith function and otologic symptoms was analyzed. Of the 28 patients with head trauma, 18 complained of dizziness and 12 experienced hearing loss, including 6 patients who complained of both. On defining otolith dysfunction as an abnormal cVEMP or abnormal SVV, a significant difference in otolith dysfunction existed between the groups with and without dizziness [72 (13/18) vs. 20% (2/10)]. In contrast, no significant difference in otolith dysfunction was detected between the abnormal and normal hearing groups. A significant number of the patients who complained of nonspecific dizziness after trauma had abnormal otolith function. After trauma, when patients complain of dizziness, vestibular function tests, including otolith function tests, should be considered. [ABSTRACT FROM AUTHOR]

Glycated albumin (GA) is recognized as a reliable marker for short-term glycemic monitoring in diabetic patients. We investigated the clinical relevance of GA and the ratio of GA to glycated hemoglobin (A1c) in Korean type 2 diabetic patients. In this retrospective study, we compared A1c, GA, and the GA/A1c ratio and analyzed the relationship between glycemic indices and various parameters in 1,038 Korean type 2 diabetic patients. The patients were divided into two groups: a stably maintained A1c group whose A1c levels did not fluctuate by more than 0.5% for at least 6 months and an unstably maintained A1c group whose A1c levels fluctuated by more than 0.5%. Serum GA was strongly correlated with A1c in both groups. Fasting plasma glucose and postprandial glucose were correlated with GA in unstably maintained A1c group, whereas they were correlated with A1c in stably maintained A1c group. The GA/A1c ratio tended to increase as A1c increased. Postprandial glucose and body mass index affected the GA/A1c ratio. Our data show that serum GA may be a more useful glycation index than A1c for monitoring glycemic control in type 2 diabetic patients with fluctuating and poorly controlled glycemic excursions. [ABSTRACT FROM AUTHOR]

Purpose: Researchers have been studying the mechanisms by which metastasis can be prevented via blocking the hematogenous and the lymphatic routes for a long time now. However, metastasis is still the single most challenging obstacle for successful cancer management. In a new twist that may require some retooling of this established approach, we investigated the hypothesis that tumor metastases can occur via an independent fluid-conducting system called the primo-vascular system.Procedures: The dissemination and growth of near-infrared quantum dot (NIR QD)-electroporated cancer cells in metastatic sites were investigated using in vivo multispectral imaging techniques.Results: Our results show that the NIR QD-labeled cancer cells were able to migrate through not only the blood vascular and lymphatic systems but also the primo-vascular system extending from around the tumor to inside the abdominal cavity. Furthermore, the NIR QD-labeled cancer cells, which had been seeded intraperitoneally, specifically infiltrated the primo-vascular system in the omentum and in the gonadal fat.Conclusions: These findings strongly suggest that the primo-vascular system may be an additional metastasis route, complementing the lymphatic and hematogenous routes, which facilitate the dissemination and colonization of cancer cells at secondary sites. [ABSTRACT FROM AUTHOR]

The inhibitor kappaB kinase β (IKK β) is a serine-threonine protein kinase that is critically involved in the activation of the transcription factor nuclear factor kappa B (NF-κB) in response to various inflammatory stimuli. IKK β-selective inhibitors could prove useful for the treatment of inflammatory diseases. In the absence of structural information, a ligand-based approach can serve as an alternative to the virtual screening of large databases. We have developed a 3D QSAR pharmacophore model based on 23 IKK β inhibitors with 3 nM ≤ IC ≤ 50000 nM. A four-feature pharmacophore containing a hydrophobic (Hy) feature, two ring aromatic (RA) features, and a hydrogen bond donor (D) feature was constructed. It yielded a correlation coefficient of 0.93 with experimentally determined activity data, and a correlation coefficient of 0.77 with training set activity data. The best hypothesis, Hypo 1, was validated by estimating the activities of 136 compounds in a test set. As well as the correlation analysis and test set activity estimation, a Fisher's validation test was conducted at the 95% confidence level. The pharmacophore model's specificity and selectivity were determined in an exhaustive enrichment study. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Objectives: To assess the extent of exposure to lead, cadmium, and mercury in the Korean general adult population using a representative sample. Methods: We studied blood concentrations of three heavy metals in a representative sample of 1,997 Koreans as part of the Third Korean National Health and Nutrition Examination Survey (KNHANES III) performed in 2005. Results: The geometric means of the blood lead, cadmium, and mercury concentrations were 2.61 μg/dL, 1.53 μg/L, and 4.15 μg/L, respectively [95% confidence intervals (CIs), 2.50-2.71, 1.48-1.58, and 3.94-4.36, respectively]. Women had significantly lower blood lead and mercury concentrations in adjusted and unadjusted analyses but no difference between genders was observed in blood cadmium analysis. The geometric means of blood lead and mercury levels were higher in subjects older than 40 years than in those younger than 40 years. Smoking status only affected the blood lead concentration, with this being higher in smokers than in nonsmokers. Blood cadmium levels did not differ with demographic and lifestyle variables after covariate adjustment. Blood mercury concentrations were higher in those who consumed alcohol and also increased with the frequency of fish consumption. Conclusions: This biomonitoring study of blood heavy metals in the Korean general population as part of KNHANES III provides important reference data stratified by demographic and lifestyle factors that will be useful for the ongoing surveillance of environmental exposure of the Korean general population to heavy metals. [ABSTRACT FROM AUTHOR]

β-catenin is a component of the adhesion complex linking cadherin and actin cytoskeleton, as well as a major mediator of the Wnt pathway, which is a critical signal cascade regulating embryonic development, cell polarity, carcinogenesis, and stem cell function. NF-κB functions as a key regulator of immune responses and apoptosis, and mutations in NF-κB signaling can lead to immune diseases and cancers. We previously showed that NF-κB-mediated modulation of β-catenin/Tcf signaling is mediated by leucine zipper tumor suppressor 2 (Lzts2) and that lzts2 expression is differentially regulated in various cancer cells. Its functional significances, however, are poorly understood. We showed that NF-κB-induced modulation of β-catenin/Tcf pathway is regulated by lzts2 expression in mesenchymal stem cells (MSCs) and several cancer cells, and that NF-κB-induced lzts2 expression is differentially regulated among cancer cell types. Here, using a promoter-reporter assay and EMSA, we demonstrate that NF-κB regulates lzts2 transcription by directly binding to the lzts2 promoter, and that NF-κB-induced lzts2 transcription differs by cell types. Modulation of lzts2 expression by lentiviral techniques affected proliferation and tumorigenicity of several cancer cell lines such as breast, colon, prostate cancer, and glioma, but did not affect cisplatin sensitivity or cell migration. Our data indicate that lzts2 expression is transcriptionally regulated by NF-κB activities, and the modulation of lzts2 expression affects cell proliferation and tumor growth through the Wnt/β-catenin pathway in various cancer cell lines. [ABSTRACT FROM AUTHOR]

A rapid and sensitive liquid chromatography–tandem mass spectrometry method was developed and validated for quantification of lamotrigine in human serum. After a simple protein precipitation using acetonitrile, the analytes were separated on a Shideido 150 mm × 2.0 mm, 5 μm Capcell Pak C18 MG column using 70% acetonitrile as mobile phase at a flow rate of 200 μl/min. Lamotrigine was eluted at 1.98 min, ionized using electrospray ionization source, and then detected by multiple reaction monitoring mode. The precursor to product ion transitions of m/z 256.1–109.0 was used to quantify. The analytical measurement range is from 0.1 to 20 μg/ml and the upper clinical reportable range is chosen to be 100 μg/ml. The method was successfully employed in a clinical application. [ABSTRACT FROM AUTHOR]

Proteasomes, the primary mediators of ubiquitin–protein conjugate degradation, are regulated through complex and poorly understood mechanisms. Here we show that USP14, a proteasome-associated deubiquitinating enzyme, can inhibit the degradation of ubiquitin–protein conjugates both in vitro and in cells. A catalytically inactive variant of USP14 has reduced inhibitory activity, indicating that inhibition is mediated by trimming of the ubiquitin chain on the substrate. A high-throughput screen identified a selective small-molecule inhibitor of the deubiquitinating activity of human USP14. Treatment of cultured cells with this compound enhanced degradation of several proteasome substrates that have been implicated in neurodegenerative disease. USP14 inhibition accelerated the degradation of oxidized proteins and enhanced resistance to oxidative stress. Enhancement of proteasome activity through inhibition of USP14 may offer a strategy to reduce the levels of aberrant proteins in cells under proteotoxic stress. [ABSTRACT FROM AUTHOR]

This article reports on titanium dioxide (TiO)-coated nanofibers deposited on a filter surface by the electrospinning process. After depositing a micrometer-thick film of polyamide 11 nanofibers on polypropylene fabric, TiO nanoparticles can be directly electrosprayed onto the nanofibers. X-ray diffraction and Raman spectroscopy showed minimal change in the phase composition (anatase and rutile) and no change in the particle size of nanocrystalline TiO after coating. Scanning electron microscopy demonstrated that nanofibers were uniformly coated by titanium dioxide nanoparticles without agglomeration. TiO-coated filters showed excellent photocatalytic-bactericidal activity and photo-induced hydrophilicity. [ABSTRACT FROM AUTHOR]

In yeast and mammals, the Yip/PRA1 family of proteins has been reported to facilitate the delivery of Rab GTPases to the membrane by dissociating the Rab–GDI complex during vesicle trafficking. Recently, we identified OsPRA1, a plant Yip/PRA1 homolog, as an OsRab7-interacting protein that localizes to the prevacuolar compartment, which suggests that it plays a role in vacuolar trafficking of plant cells. Here, we show that OsPRA1 is essential for vacuolar trafficking and that it has molecular properties that are typical of the Yip/PRA1 family of proteins. A trafficking assay using Arabidopsis protoplasts showed that the point mutant OsPRA1 strongly inhibits the vacuolar trafficking of cargo proteins, but has no inhibitory effect on the plasma membrane trafficking of H-ATPase-GFP, suggesting its specific involvement in vacuolar trafficking. Moreover, OsPRA1 was shown to be an integral membrane protein, suggesting that its two hydrophobic domains may mediate membrane integration, and its cytoplasmic N- and C-terminal regions were found to be important for binding to OsRab7. OsPRA1 also interacted with OsVamp3, implying its involvement in vesicle fusion. Finally, we used a yeast expression system to show that OsPRA1 opposes OsGDI2 activity and facilitates the delivery of OsRab7 to the target membrane. Taken together, our results support strongly that OsPRA1 targets OsRab7 to the tonoplast during vacuolar trafficking. [ABSTRACT FROM AUTHOR]

In this study, an effective method for reliability-based design optimization is proposed enhancing sequential optimization and reliability assessment (SORA) method by a family of methods of moving asymptotes (MMA) approximations. In SORA, reliability estimation and deterministic optimization are performed sequentially. And the sensitivity and function value of probabilistic constraint at the most probable point (MPP) are obtained in the process of finding reliability information. In this study, a family of MMA approximations are constructed by utilizing the sensitivity and function value of the probabilistic constraint at the MPP. So, no additional evaluation of the probabilistic constraint is required in constructing MMA approximations. Moreover, no additional evaluation of the probabilistic constraint is required in the deterministic optimization of SORA by using a family of MMA approximations. The efficiency and accuracy of the proposed method were verified through numerical examples. [ABSTRACT FROM AUTHOR]

Axonal pathology has been clearly implicated in neurodegenerative diseases making the compartmental culture of neurons a useful research tool. Primary neurons have already been cultured in compartmental microfluidic devices but their derivation from an animal is a time-consuming and difficult work and has a limit in their sources. Embryonic stem cell (ESC)-derived neurons (ESC_Ns) overcome this limit, since ESCs can be renewed without limit and can be differentiated into ESC_Ns by robust and reproducible protocols. In this research, ESC_Ns were derived from mouse ESCs in compartmental microfluidic devices, and their axons were isolated from the somal cell bodies. Once embryoid bodies (EBs) were localized in the microfluidic culture chamber, ESC_Ns spread out from the EBs and occupied the cell culture chamber. Their axons traversed the microchannels and finally were isolated from the somata, providing an arrangement comparable to dissociated primary neurons. This ESC_N compartmental microfluidic culture system not only offers a substitute for the primary neuron counterpart system but also makes it possible to make comparisons between the two systems. [ABSTRACT FROM AUTHOR]

Drought is one of the most important constraints on the growth and productivity of many crops, including soybeans. However, as a primary sensing organ, the plant root response to drought has not been well documented at the proteomic level. In the present study, we carried out a proteome analysis in combination with physiological analyses of soybean roots subjected to severe but recoverable drought stress at the seedling stage. Drought stress resulted in the increased accumulation of reactive oxygen species and subsequent lipid peroxidation. The proline content increased in drought-stressed plants and then decreased during the period of recovery. The high-resolution proteome map demonstrated significant variations in about 45 protein spots detected on Comassie briliant blue-stained 2-DE gels. Of these, 28 proteins were identified by mass spectrometry; the levels of 5 protein spots were increased, 21 were decreased and 2 spots were newly detected under drought condition. When the stress was terminated by watering the plants for 4 days, in most cases, the protein levels tended towards the control level. The proteins identified in this study are involved in a variety of cellular functions, including carbohydrate and nitrogen metabolism, cell wall modification, signal transduction, cell defense and programmed cell death, and they contribute to the molecular mechanism of drought tolerance in soybean plants. Analysis of protein expression patterns revealed that proteins associated with osmotic adjustment, defense signaling and programmed cell death play important roles for soybean plant drought adaptation. The identification of these proteins provides new insight that may lead to a better understanding of the molecular basis of the drought stress responses. [ABSTRACT FROM AUTHOR]

Previously, the wheat non-specific lipid transfer proteins (TaLTP), members of a small multigene family, were reported to evidence a complex pattern of expression regulation. In order to assess further the expression diversity of the TaLTP genes, we have attempted to evaluate their expression profiles in responses to abiotic stresses, using semi-quantitative RT-PCR. The expression profiles generated herein revealed that the TaLTP genes in group A evidenced highly similar responses against abiotic stresses, whereas differential expression patterns among genes in each group were also observed. A total of seven promoters were fused to a GUS reporter gene and the recombinants were introduced into Arabidopsis, while three promoters evidenced non-detectible GUS activity. The promoters of TaLTP1, TaLTP7, and TaLTP10 included in group A drove strong expressions during plant development with overlapping patterns, in large part, but also exhibited distinct expression pattern, thereby suggesting subfunctionalization processing over evolutionary time. However, only trace expression in cotyledons, young emerged leaves, and epidermal cell layers of flower ovaries was driven by the promoter of TaLTP3 of group B. These results indicate that their distinct physiological functions appear to be accomplished by a subfunctionalization process involving degenerative mutations in regulatory regions. [ABSTRACT FROM AUTHOR]

Intra-articular synovial lipoma is rare and clinically manifested mostly by mass effect and occasionally by torsion of the stalk. Patellar dislocation rarely occurs owing to a mass effect of intra-articular tumor of the knee joint. The authors present a case of large intra-articular synovial lipoma at the lateral gutter of the knee joint, which presents as patellar dislocation. A 19-year-old man visited our clinic due to pain and limitation of motion owing to mass at his left knee. MRI revealed an intra-articular soft tissue mass at the lateral gutter of the knee joint with considerable mass effect displacing patella from the trochlear groove. Excisional biopsy confirmed the diagnosis of lipoma, and the final diagnosis was intra-articular synovial lipoma with clinical information. The final radiograph showed well-aligned patella on the trochlear groove. After marginal excision, there was no recurrence or tumor-related morbidity. [ABSTRACT FROM AUTHOR]

Batch photodegradation of pentachlorophenol (PCP) was conducted with ultraviolet irradiation. The main intermediates were identified as 2,3,5,6-tetrachlorophenol, 2,3,4,6-tetrachlorophenol and 2,5-dichlorophenol. Based on the density functional theory, atomic charge values were applied to reveal the photodegradation pathway. A comparison of the results of the experiment confirms that PCP molecules are dechlorinated in the descending order of their atomic charge values. From these results, it appears that determining the atomic charge values of organohalogen compounds is a promising method for predicting the dechlorination position in photodegradation. [ABSTRACT FROM AUTHOR]

Primary spinal malignant melanoma is an extremely rare condition. We here describe a case of a 71-year-old Asian female presenting with left upper extremity tingling sensation. Computed tomography (CT) showed a homogeneously enhanced mass occupying the left neural foramen at the C6-7 level. Magnetic resonance imaging revealed enhanced mass in intra- and extradural space compressing the spinal cord at this level. It also widened the neural foramen mimicking neurofibroma or schwannoma. Partial resection of the mass was performed. Pathologic diagnosis of the mass was malignant melanoma. Postoperative whole body positron emission tomography/CT scan demonstrated an intense 18F-FDG uptake at the residual mass site without abnormal uptake at other sites in the body. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNP) are among the fastest growing product categories in the nanotechnology industry. Despite the importance of AgNP in consumer products and clinical applications, relatively little is known regarding AgNP toxicity and its associated risks. We investigated the effects of AgNP on gene expression in the mouse brain using Affymetrix Mouse Genome Arrays. C57BL/6 mice were exposed to AgNP (geometric mean diameter, 22.18 ± 1.72 nm; 1.91 × 107 particles/cm3) for 6 h/day, 5 days/week using the nose-only exposure system for 2 weeks. Total RNA isolated from the cerebrum and cerebellum was subjected to hybridization. From over 39,000 probe sets, 468 genes in the cerebrum and 952 genes in the cerebellum were identified as AgNP-responsive (one-way analysis of variance; p < 0.05). The largest groups of gene products affected by AgNP exposure included 73 genes in the cerebrum and 144 genes in the cerebellum. AgNP exposure modulated the expression of several genes associated with motor neuron disorders, neurodegenerative disease, and immune cell function, indicating potential neurotoxicity and immunotoxicity associated with AgNP exposure. Real-time PCR data for five genes analyzed from whole blood showed good correlation with the observed changes in the brain. Following rigorous validation and substantiation, these genes may assist in the development of surrogate markers for AgNP exposure and/or toxicity. [ABSTRACT FROM AUTHOR]

Clp-family proteins are prototypes for studying the mechanism of ATP-dependent proteases because the proteolytic activity of the ClpP core is tightly regulated by activating Clp-ATPases. Nonetheless, the proteolytic activation mechanism has remained elusive because of the lack of a complex structure. Acyldepsipeptides (ADEPs), a recently discovered class of antibiotics, activate and disregulate ClpP. Here we have elucidated the structural changes underlying the ClpP activation process by ADEPs. We present the structures of Bacillus subtilis ClpP alone and in complex with ADEP1 and ADEP2. The structures show the closed-to-open-gate transition of the ClpP N-terminal segments upon activation as well as conformational changes restricted to the upper portion of ClpP. The direction of the conformational movement and the hydrophobic clustering that stabilizes the closed structure are markedly different from those of other ATP-dependent proteases, providing unprecedented insights into the activation of ClpP. [ABSTRACT FROM AUTHOR]

Plant 2-Cys peroxiredoxins (2-Cys Prx) has both peroxidase and chaperon function. We overexpressed an Arabidopsis 2-Cys Prx in transgenic tall fescue ( Festuca arundinacea) plants to confer tolerance against heat and methyl viologen (MV) stress. Transgenic plants were generated by Agrobacterium-mediated genetic transformation, and integration and expression of the transgene was confirmed by Southern, northern and western blot analyses. Compared to control plants, transgenic plants had significantly less electrolyte leakage and thiobarbituric acid-reactive substances (TBARS) when exposed to heat or MV. Under heat stress (42°C), transgenic plants maintained their chlorophyll fluorescence (Fv /Fm) for 24 h while control plants lost chlorophyll fluorescence very quickly. We conclude that the high levels of 2-Cys Prx proteins in transgenic plants protect leaves from oxidative damage probably due to chaperon activity. [ABSTRACT FROM AUTHOR]

The influence of high-energy e-beam treatment at atmospheric pressure on the structure and photocatalytic activity of TiO2 was examined. Using an e-beam energy of 1 MeV and exposure in the range of 5–15 kGy, an improvement in the photocatalytic activity of TiO2 was observed. An increase in the population of C–O bonds was found in the C and O 1s states using X-ray Photoelectron Spectroscopy (XPS) suggesting that the change in the structure of the C impurities on the surface of TiO2 is closely related to the variation in the photocatalytic activity. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

To gain better insight into how soybean roots respond to waterlogging stress, we carried out proteomic profiling combined with physiological analysis at two time points for soybean seedlings in their early vegetative stage. Seedlings at the V2 stage were subjected to 3 and 7 days of waterlogging treatments. Waterlogging stress resulted in a gradual increase of lipid peroxidation and in vivo H2O2 level in roots. Total proteins were extracted from root samples and separated by two-dimensional gel electrophoresis (2-DE). A total of 24 reproducibly resolved, differentially expressed protein spots visualized by Coomassie brilliant blue (CBB) staining were identified by matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry or electrospray ionization tandem mass spectrometry (ESI-MS/MS) analysis. Of these, 14 proteins were upregulated; 5 proteins were decreased; and 5 were newly induced in waterlogged roots. The identified proteins include well-known classical anaerobically induced proteins as well as novel waterlogging-responsive proteins that were not known previously as being waterlogging responsive. The novel proteins are involved in several processes, i.e. signal transduction, programmed cell death, RNA processing, redox homeostasis and metabolisms of energy. An increase in abundance of several typical anaerobically induced proteins, such as glycolysis and fermentation pathway enzymes, suggests that plants meet energy requirement via the fermentation pathway due to lack of oxygen. Additionally, the impact of waterlogging on the several programmed cell death- and signal transduction-related proteins suggest that they have a role to play during stress. RNA gel blot analysis for three programmed cell death-related genes also revealed a differential mRNA level but did not correlate well with the protein level. These results demonstrate that the soybean plant can cope with waterlogging through the management of carbohydrate consumption and by regulating programmed cell death. The identification of novel proteins such as a translation initiation factor, apyrase, auxin-amidohydrolase and coproporphyrinogen oxidase in response to waterlogging stress may provide new insight into the molecular basis of the waterlogging-stress response of soybean. [ABSTRACT FROM AUTHOR]

The aim of the study was to assess the difference in clinical characteristics and postsurgical outcomes between children and adults who have undergone temporal lobectomy (TL). We retrospectively reviewed the medical records of 52 patients who had undergone TL between 2006 and 2008. Nineteen patients were classified as children (≤18 years old), and 33 patients were classified as adults (>18 years old) according to the age when TL had been performed. Twelve of 19 (63.2%) children and 24 of 33 (72.7%) adults became seizure free. Rapid secondary generalization such as generalized tonic or tonic–clonic seizures showed a tendency to be more prominent in children (four of 19, 21.1%) than in adults (three of 33, 9.1%). Patients in childhood had significantly more multifocal discharges on interictal electroencephalography (EEG) (42.1%) compared to adults (15.2%, p = 0.014). The mean extent of surgical excision was 5.0 cm in children and 4.1 cm in adults ( p = 0.001). The incidence of hippocampal sclerosis, the most common pathologic finding in the two groups, was 57.9% (11 of 19) in children and 78.8% (26 of 33) in adults. Malformations of cortical development were significantly more frequent in children (nine of 19, 47.4%) than in adults (seven of 33, 21.2%). Dual pathology was found in 31.6% of children and in 12.1% of adults. The intelligence quotient and memory quotient values in children with temporal lobe resection remained nearly steady during follow-up period without significant decline. Patients undergoing TL during childhood compared to during adulthood had distinctively different interictal EEG, resectional extents, and pathologic findings. [ABSTRACT FROM AUTHOR]

Islet transplantation is a potential treatment for type 1 diabetes. Currently, islet graft survival is measured using invasive methods to determine blood glucose, insulin, and C-peptide levels, even though these variables have limited value. To trace β-cell survival and functional status, we constructed an adenovirus/adenoassociate virus hybrid vector (Hyb-DR) carrying two reporter genes, luciferase and green fluorescent protein (GFP), linked by the internal ribosome entry site and driven by the rat insulin II promoter. Luciferase activity increased and positive GFP expression was observed in β-cell lines (MIN6N8 and INS-1E) infected with Hyb-DR. Using an in vivo imaging instrument, the GFP signal was detected in the flanks of nude mice 2 weeks after transplanting Hyb-DR-infected MIN6 cells into the kidney capsule. Coinfection of Hyb-DR with plasmids carrying β-cell-specific transcription factors also resulted in expression of luciferase and GFP in the non-β-cell lines (HepG2, FL83B, and YGIC5). Thus, the dual reporter system provided quantitative and visual information about the functionality of the islet mass and activation of the insulin gene. [ABSTRACT FROM AUTHOR]