bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting pulmonary adenocarcinoma outcome based on a cytology grading system
Authors: Sigel Carlie S. , Rudomina Dorota E. , Sima Camelia S. , Rekhtman Natasha , Travis William D. , Geisinger Kim R. , Moreira Andre L.
Published: September 2011

BACKGROUND:

Pulmonary adenocarcinoma (AD) has a variety of architectural patterns. Recently, a 3‐tiered histological pattern‐based grading system was developed for stage I lung AD, stratifying patients into low, intermediate, and high risk for recurrence. However, cytology may serve as the primary method for diagnosis in patients with inoperable disease. Attempts to correlate architecture between parallel cytological and histological preparations have not been successful. Therefore, we evaluated cytomorphologic features of previously histologically graded AD to identify features of potential prognostic significance.

METHODS:

One hundred and thirteen fine‐needle aspirations with excised adenocarcinomas were reviewed. In the liquid‐based preparation, we evaluated cell arrangements (flat sheets vs 3‐D clusters vs single cells), nuclear features (size variability, shape, and contour), nucleoli (prominent or inconspicuous), presence of nuclear inclusions, chromatin (fine, coarse, or clumped), and quality of background. The features were tested by multivariate analysis to identify associations with histological grade and disease‐free survival (DFS), and a cytological score was generated.

RESULTS:

Nuclear size, chromatin pattern, and nuclear contours showed a significant association with histological grade and DFS. These features were included in the composite cytological score (range, 0‐5). By grouping the cytological scores, we stratified the tumors into low (median DFS, 100%), intermediate (median DFS, 78%), and high (median DFS, 55%) rate of recurrence (P = .008). There was a good correlation with the histological grading system.

CONCLUSIONS:

In liquid‐based preparations, distinctive cytological features of pulmonary adenocarcinoma correlate with levels of histological differentiation and can be combined into a score with prognostic significance. Cancer (Cancer Cytopathol) 2012. © 2011 American Cancer Society.
Microglial regulation of cholinergic differentiation in the basal forebrain
Authors: Jonakait G. Miller , Pratt Lorelei , Acevedo Giselles , Ni Li
Published: September 2011

Because inflammation during pregnancy can lead to neurodevelopmental anomalies, we investigated the role of inflamed microglia on cholinergic precursors in the rat embryonic basal forebrain (BF) cultured on embryonic day 15. Conditioned medium (CM) taken from microglia stimulated variously (microglial CM; MCM) increased activity of choline acetyltransferase (ChAT), the enzyme responsible for acetylcholine biosynthesis and a phenotypic hallmark of the cholinergic neuron. There was a concomitant decline in glutamic acid decarboxylase expression. Of stimulators tested, only β‐amyloid failed to produce effective MCM. Infection with a Lac‐Z‐containing retrovirus revealed that MCM promoted cholinergic differentiation from undifferentiated precursors in the population. Several candidates were tested for their ability to mimic MCM. Mature nerve growth factor (NGF) did not mimic MCM, but acted synergistically with it to promote enormous increases in ChAT activity. However, a microglial cell line produced high‐molecular weight forms of NGF (pro‐NGF) that were lethal to mature cholinergic neurons. Although bone morphogenetic proteins (BMP) 2, 4, and 9 increased ChAT activity dose‐dependently, noggin did not inhibit the effects of the MCM, suggesting that BMPs were not the only active factor(s) in the MCM. Embryonic microglia isolated following maternal inflammation produced a variety of immune system cytokines and chemokines. One of these, interleukin‐6 (IL‐6), was tested for its ability to promote cholinergic differentiation. Although IL‐6 alone did not mimic the action of MCM, neutralization of it inhibited MCM effectiveness. Thus, following maternal inflammation, a complex microglial‐derived cocktail of factors can promote excess cholinergic differentiation in the embryonic BF. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 857–864, 2012
Zinc Complexes with Guanidine–Pyridine Hybrid Ligands – Guanidine Effect and Catalytic Activity
Authors: Börner Janna , dos Santos Vieira Ines , Jones Matthew D. , Döring Artjom , Kuckling Dirk , Flörke Ulrich , Herres‐Pawlis Sonja
Published: September 2011

Two new series of guanidine–pyridine ligands have been synthesised by the reaction of various chloroformamidinium chlorides with 8‐aminoquinoline or 2‐picolylamine. The ligands were treated with either zinc chloride or zinc acetate to prepare the corresponding complexes, which were tested as initiators in the solvent‐free ring‐opening polymerisation of d,l‐lactide. The effect of the guanidine ligand on the catalytic activity of the zinc complexes was investigated. A great number of the synthesised complexes showed appreciable polymerisation activity. 13 new zinc guanidine complexes have been structurally characterised, including the first examples of structures comprising a tetraethylguanidine unit. The experimental results were complemented by a density functional study, which has probed the influence of substituents at the guanidine unit. Especially for the tetraethylguanidine systems, insights into the strength of delocalisation within guanidine moieties are provided.
Microfluidic mixing using contactless dielectrophoresis
Authors: Salmanzadeh Alireza , Shafiee Hadi , Davalos Rafael V. , Stremler Mark A.
Published: September 2011

The first experimental evidence of mixing enhancement in a microfluidic system using contactless dielectrophoresis (cDEP) is presented in this work. Pressure‐driven flow of deionized water containing 0.5 μm beads was mixed in various chamber geometries by imposing a dielectrophoresis (DEP) force on the beads. In cDEP the electrodes are not in direct contact with the fluid sample but are instead capacitively coupled to the mixing chamber through thin dielectric barriers, which eliminates many of the problems encountered with standard DEP. Four system designs with rectangular and circular mixing chambers were fabricated in PDMS. Mixing tests were conducted for flow rates from 0.005 to 1 mL/h subject to an alternating current signal range of 0–300 V at 100–600 kHz. When the time scales of the bulk fluid motion and the DEP motion were commensurate, rapid mixing was observed. The rectangular mixing chambers were found to be more efficient than the circular chambers. This approach shows potential for mixing low diffusivity biological samples, which is a very challenging problem in laminar flows at small scales.
LOH on 10p14‐p15 targets the PFKFB3 gene locus in human glioblastomas
Authors: Fleischer Michael , Kessler Renate , Klammer Angelika , Warnke Jan‐Peter , Eschrich Klaus
Published: September 2011

Loss of heterozygosity (LOH) on chromosome arm 10p is very common in high‐grade gliomas and is, among others, concentrated on the region 10p14‐p15. Presence of multiple tumor suppressor genes is assumed, but until now only Krüpple‐like transcription factor 6 (KLF6) has been suggested as possible target of LOH in this region. On the basis of the fact that the splice variant 4 (UBI2K4) of the PFKFB3 gene, located in 10p15.1, inhibits the anchorage‐independent growth of U87 glioblastoma cells, we hypothesized that PFKFB3 is a target gene of LOH in glioblastomas. In this study, we analyzed 40 glioblastomas for LOH in 10p15, including the PFKFB3 and KLF6 loci, by PCR‐based microsatellite analysis. We detected LOH of PFKFB3 in 55% (22/40) of glioblastomas. LOH of KLF6, mapped 2.5 cM telomerically to the PFKFB3 locus, was not stringently correlated to the PFKFB3 LOH. The allelic deletion of PFKFB3 resulted in a decrease of PFKFB3 mRNA level accompanied by a lower PFKFB3 protein level. The expression of growth‐inhibiting splice variant UBI2K4 was effectively reduced in glioblastomas with PFKFB3 LOH and a positive correlation with overall PFKFFB3 expression was observed. The PFKFB3 LOH as well as the resulting low UBI2K4 expression level was associated with a poor prognosis of glioblastoma patients. We conclude that LOH on 10p14‐p15 in glioblastomas targets PFKFB3 and in particular splice variant UBI2K4, a putative tumor suppressor protein in glioblastomas. © 2011 Wiley Periodicals, Inc.
Relationship between apathy and diffusion tensor imaging metrics of the brain in Alzheimer's disease
Authors: Ota Miho , Sato Noriko , Nakata Yasuhiro , Arima Kunimasa , Uno Masatake
Published: September 2011

Objective

Alzheimer's disease (AD) research has largely concentrated on the study of cognitive decline, but the associated behavioral and neuropsychiatric symptoms are of equal importance in the clinical profile of the disease. Apathy is the most common neuropsychiatric manifestation in AD. Clinical, multimodal neuroimaging studies and pathologic studies of apathy in AD have suggested an association with frontal dysfunction but without a definitive localization. In this study, we examined the association between apathy and white matter integrity using diffusion tensor imaging (DTI).

Methods

Twenty‐one AD patients underwent DTI and neuropsychiatric and cognitive assessments. All fractional anisotropy (FA) maps were normalized to the standard space, and the association between the apathy scale and DTI metrics were evaluated voxel basically.

Results

Statistical parametric mapping analysis showed that there were statistically negative correlations between the apathy scale and FA values in the right anterior cingulate, right thalamus, and bilateral parietal regions using age, Mini‐Mental State Examination score and sex as nuisance variables.

Conclusions

Apathy in AD is associated with impaired white matter integrity in the anterior cingulate and medial thalamus. These results reinforce the confluence of evidence from other investigational modalities in implicating limbic dysfunction and related neuronal circuits in the neurobiology of apathy in AD. Copyright © 2011 John Wiley & Sons, Ltd.
HEALTH SERVICE USE AMONG THE PREVIOUSLY UNINSURED: IS SUBSIDIZED HEALTH INSURANCE ENOUGH?
Authors: Decker Sandra L. , Doshi Jalpa A. , Knaup Amy E. , Polsky Daniel
Published: September 2011

Although it has been shown that gaining Medicare coverage at age 65 years increases health service use among the uninsured, difficulty in changing habits or differences in the characteristics of previously uninsured compared with insured individuals may mean that the previously uninsured continue to use the healthcare system differently from others. This study uses Medicare claims data linked to two different surveys—the National Health Interview Survey and the Health and Retirement Study—to describe the relationship between insurance status before age 65 years and the use of Medicare‐covered services beginning at age 65 years. Although we do not find statistically significant differences in Medicare expenditures or in the number of hospitalizations by previous insurance status, we do find that individuals who were uninsured before age 65 years continue to use the healthcare system differently from those who were privately insured. Specifically, they have 16% fewer visits to office‐based physicians but make 18% and 43% more visits to hospital emergency and outpatient departments, respectively. A key question for the future may be why the previously uninsured seem to continue to use the healthcare system differently from the previously insured. This question may be important to consider as health coverage expansions are implemented. Copyright © 2011 John Wiley & Sons, Ltd.
On the relative role of upslope and downslope topography for describing water flow path and storage dynamics: a theoretical analysis
Authors: Lanni C. , McDonnell J. J. , Rigon R.
Published: September 2011

Many current conceptual rainfall‐runoff and shallow landslide stability models are based on the topographic index concept derived from the steady‐state assumption for subsurface water flow dynamics and the hypothesis that the surface gradient is a good approximation for the gradient of the total hydraulic head. However, increasing field evidence from sites around the world has shown poor correlations between the topographic index and the patterns of soil water storage. Here we present a new, smoothed, dynamic topographic index and test the ability of this index to reproduce spatial patterns of wetness areas and storage as provided by a distributed, physically based, Boussinesq equation (BEq) solver. Our results show that the new smoothed dynamic topographic index outperforms previous, locally computed indices in the estimation of storage dynamics, resulting in less fragmented and disconnected spatial patterns of storage. Our new dynamic index is able to capture both the upslope and downslope controls on water flow and approximates storage dynamics across scales. The new index is compatible with high‐resolution topographic data. We encourage the use of our smoothed dynamic topographic index to describe the lateral subsurface flow component in landslide generation models and conceptual rainfall‐runoff models, especially when high‐resolution digital elevation models are available. Copyright © 2011 John Wiley & Sons, Ltd.
Appraisal of Budyko formula in calculating long‐term water balance in humid watersheds of southern China
Authors: Xiong Lihua , Guo Shenglian
Published: September 2011

The Budyko formula for estimating the long‐term average annual evaporation is applied to calculate the long‐term water balance in 29 humid watersheds of southern China. As a result of overestimation of evaporation, the long‐term average annual runoff is underestimated, with the Nash‐Sutcliffe efficiency (NSE) at just − 17%. A one‐variable linear regression model is employed to find that the Budyko scatter and the relative errors of Budyko runoff and evaporation estimates are all closely related to the long‐term aridity index. Through combining the original Budyko formula with the different linear regression models for estimating the Budyko estimation errors, three forms of revised Budyko equation for estimating the long‐term average annual runoff are derived, with all their NSE values to be around 66%. After calibration, both one‐parameter Turc‐Pike and one‐parameter Fu equations lead to the NSE value of 60% in estimating long‐term average annual runoff. Two conclusions are made, with the first one being that, the nonparametric Budyko formula, although very intuitive and very simple, does not apply well in calculating long‐term water balance in 29 humid watersheds in southern China. The second one is that, the parametric evaporation formulae, with locally optimized parameter values, can achieve better accuracy in estimating long‐term average annual evaporation and runoff than the nonparametric Budyko evaporation formula. Copyright © 2011 John Wiley & Sons, Ltd.
Microsatellite instability in sporadic gastric cancer: its prognostic role and guidance for 5‐FU based chemotherapy after R0 resection
Authors: An Ji Yeong , Kim Hyunki , Cheong Jae‐Ho , Hyung Woo Jin , Kim Hoguen , Noh Sung Hoon
Published: September 2011

This study investigated whether MSI status can be used as a prognostic biomarker and whether it is helpful for predicting which patients will benefit from 5‐FU based adjuvant chemotherapy. Between 2005 and 2008, an MSI status examination was performed in 1,990 gastric cancer patients who had undergone curative gastrectomy for gastric adenocarcinoma. MSI was analyzed by PCR amplification with fluorescent dye‐labeled primers of mononucleotide markers (BAT25 and BAT26) and dinucleotide markers (D5S346, D2S123 and D17S250) specific to the microsatellite loci. Patients with MSI‐H tumors accounted for 8.5% (n = 170) of the total study population. They tended to be older and female and to have distal tumor location, lower tumor stage, intestinal type of Lauren classification and differentiated histological type. The disease‐free survival curves showed no significant differences between MSS/MSI‐L and MSI‐H patients at each stage of I, II, III and IV. In gastric cancer patients with stage II and III, 5‐FU‐based adjuvant chemotherapy showed better disease‐free survival in the MSS/MSI‐L group, but showed no benefits in the MSI‐H group. By multivariate analysis, patients with MSS/MSI‐L tumors benefited from 5‐FU‐based adjuvant chemotherapy in terms of tumor disease‐free survival. MSI status in gastric cancer is not itself a prognostic indicator. However, it appears to be a possible guidance for the use of 5‐FU‐based chemotherapy in stage II and III gastric cancers after R0 resection.
The novel indole compound SK228 induces apoptosis and FAK/Paxillin disruption in tumor cell lines and inhibits growth of tumor graft in the nude mouse
Authors: Huang Sin‐Ming , Hsu Pei‐Chun , Chen Mei‐Yu , Li Wen‐Shan , More Shivaji V. , Lu Kwok‐Tung , Wang Yi‐Ching
Published: September 2011

Drugs in clinical use with indole structure exhibit side effects. Therefore, to search for indole compounds with more efficacy and less side effect for cancer therapy, we developed a novel indole compound SK228 and examined its effects and mechanisms on antitumor growth and invasion inhibition in cell and tumor xenografts in nude mice models. SK228 significantly inhibited growth of different lung and esophageal cancer cell lines at sub‐micromolar range, but not normal lung cells. SK228 induced DNA damages mainly by producing reactive oxygen species (ROS) resulting in apoptosis. SK228 treatment increased the release of cytochrome c into the cytosol along with the increased activity of caspase‐3 and ‐9 without affecting caspase‐8, whereas these effects were attenuated by ROS inhibitor. The expression levels of BCL‐2 family regulators were also affected. Moreover, low‐dose SK228 significantly reduced the invasion of cancer cells. The active phosphorylated form of FAK/Paxillin signaling pathway proteins and active form of RhoA were decreased. Moreover, the F‐actin cytoskeleton was disrupted after low‐dose SK228 treatment. Growth of an A549 tumor cell xenograft was markedly inhibited without significant side effects. SK228‐induced apoptosis was confirmed by terminal deoxynucleotidyl transferase dUTP nick end labeling assay and immunohistochemistry of cleaved caspase‐3 in tumors from treated mice. Our study provides the first evidence that SK228 exhibits cancer cell‐specific cytotoxicity by inducing mitochondria‐mediated apoptosis. In addition, SK228 inhibits cancer cell invasion via FAK/Paxillin disruption at noncytotoxic doses. SK228 can be further tested as a pharmaceutical compound for cancer treatment.
Inflammation regulates microRNA expression in cooperation with p53 and nitric oxide
Authors: Mathé Ewy , Nguyen Giang H. , Funamizu Naotake , He Peijun , Moake Matthew , Croce Carlo M. , Hussain S. Perwez
Published: September 2011

microRNA (miRNA) are small non‐coding RNA targeting mRNAs leading to their instability and diminished translation. Altered expression of miRNA is associated with cancer. Inflammation and nitric oxide modulates the development of lymphomas in p53 knockout mice and there exists a negative feedback loop between p53 and NOS2. Using a genetic strategy, we tested the hypothesis that inflammation‐induced oxidative and nitrosative stress modulates miRNA expression in mouse model deficient in either p53 or NOS2. Mice treated with Corynebacterium parvum (C.
parvum), to induce inflammation, clearly separated from controls by their miRNA profiles in wild‐type, p53‐ and NOS2‐knockout genetic backgrounds. C.
parvum‐induced inflammation significantly (p < 0.005) increased miR‐21, miR‐29b and miR‐34a/b/c and decreased (p < 0.005) mir‐29c and mir‐181a/c expression in the spleen of C57BL mice. However, p53‐knockout C57BL mice did not show a significant increase in the mir‐34b/c or a decrease in mir‐29c expression following C.
parvum‐induced inflammation. Expression of mir‐21, mir‐29b and mir‐181a was independent of p53‐status. NOS2‐knockout C57BL mice showed a significant increase in miR‐21 and miR‐34a/b/c and decrease in miR‐181a similar to the wild‐type (WT) mice following C. parvum‐induced inflammation. However, in contrast to the WT mice, miR‐29b/c expression was not affected following C.
parvum‐induced inflammation in NOS2 knockout mice. N‐acetyl cysteine, an anti‐oxidant, reduced the expression of miR‐21 and miR‐29b in C. parvum‐treated WT mice (p < 0.005) as compared with control C. parvum‐treated mice. These data are consistent with the hypothesis that inflammation modulates miRNA expression in vivo and the alteration in specific miRNA under an inflammatory microenvironment, can be influenced by p53 (miR‐34b/c) and NO• (29b/c).
The Critical Role of the Epidermal Growth Factor Receptor in Endochondral Ossification
Authors: Zhang Xianrong , Siclari Valerie A , Lan Shenghui , Zhu Ji , Koyama Eiki , Dupuis Holly L , Enomoto-Iwamoto Motomi , Beier Frank , Qin Ling
Published: September 2011

Loss of epidermal growth factor receptor (EGFR) activity in mice alters growth plate development, impairs endochondral ossification, and retards growth. However, the detailed mechanism by which EGFR regulates endochondral bone formation is unknown. Here, we show that administration of an EGFR-specific small-molecule inhibitor, gefitinib, into 1-month-old rats for 7 days produced profound defects in long bone growth plate cartilage characterized by epiphyseal growth plate thickening and massive accumulation of hypertrophic chondrocytes. Immunostaining demonstrated that growth plate chondrocytes express EGFR, but endothelial cells and osteoclasts show little to no expression. Gefitinib did not alter chondrocyte proliferation or differentiation and vascular invasion into the hypertrophic cartilage. However, osteoclast recruitment and differentiation at the chondro-osseous junction were attenuated owing to decreased RANKL expression in the growth plate. Moreover, gefitinib treatment inhibited the expression of matrix metalloproteinases (MMP-9, -13, and -14), increased the amount of collagen fibrils, and decreased degraded extracellular matrix products in the growth plate. In vitro, the EGFR ligand transforming growth factor α (TGF-α) strongly stimulated RANKL and MMPs expression and suppressed osteoprotegerin (OPG) expression in primary chondrocytes. In addition, a mouse model of cartilage-specific EGFR inactivation exhibited a similar phenotype of hypertrophic cartilage enlargement. Together our data demonstrate that EGFR signaling supports osteoclastogenesis at the chondro-osseous junction and promotes chondrogenic expression of MMPs in the growth plate. Therefore, we conclude that EGFR signaling plays an essential role in the remodeling of growth plate cartilage extracellular matrix into bone during endochondral ossification. © 2011 American Society for Bone and Mineral Research
Interaction between PKR and PACT mediated by LPS‐inducible NF‐κB in human gingival cells
Authors: Yoshida Kaya , Okamura Hirohiko , Hoshino Yumi , Shono Masayuki , Yoshioka Masami , Hinode Daisuke , Yoshida Hideo
Published: September 2011

The double‐stranded RNA‐dependent protein kinase (PKR) is a serine/threonine kinase expressed constitutively in mammalian cells. PKR is activated upon virus infection by double‐stranded RNA (dsRNA), and plays a critical role in host antiviral defense mechanisms. PKR is also known to regulate various biological responses, including cell differentiation and apoptosis. However, whether PKR is involved in the progress of periodontitis is not clear. The present study explained the phosphorylation of PKR by LPS in the human gingival cell line, Sa3. Expression of genes encoding LPS receptors was detected in Sa3 cells and treatment of cells with 1 µg/mL LPS for 6 h caused PKR phosphorylation. LPS elevated the expression of the protein activator of PKR (PACT) mRNA and protein, followed by the enhanced association between PACT and PKR within 3 h. In addition, LPS treatment induced the translocation of NF‐κB to the nucleus after 30 min, and inhibition of NF‐κB decreased the PACT–PKR interaction induced by LPS. The level of pro‐inflammatory cytokine mRNA, including interleukin‐6 (IL‐6) and tumor necrosis factor alpha (TNFα), appeared within 45 min and reached at the maximal levels by 90 min after the addition of LPS. This induction of pro‐inflammatory cytokines was not affected by RNAi‐mediated silencing of PKR and a pharmacological inhibitor of PKR, whereas the inhibition of NF‐κB decreased it. These results indicated that LPS induces PKR phosphorylation and the PACT–PKR association in Sa3 cells. Our results also suggest that NF‐κB is involved in the PACT–PKR interaction and the production of pro‐inflammatory cytokines in periodontitis. J. Cell. Biochem. 113: 165–173, 2012. © 2011 Wiley Periodicals, Inc.
Experimental hyperprolinemia induces mild oxidative stress, metabolic changes, and tissue adaptation in rat liver
Authors: Ferreira Andréa G.K. , da Cunha Aline A. , Machado Fernanda R. , Pederzolli Carolina D. , Dalazen Giovana R. , de Assis Adriano M. , Lamers Marcelo L. , dos Santos Marinilce F. , Dutra‐Filho Carlos S. , Wyse Angela T.S.
Published: September 2011

The present study investigated the effects of chronic hyperprolinemia on oxidative and metabolic status in liver and serum of rats. Wistar rats received daily subcutaneous injections of proline from their 6th to 28th day of life. Twelve hours after the last injection the rats were sacrificed and liver and serum were collected. Results showed that hyperprolinemia induced a significant reduction in total antioxidant potential and thiobarbituric acid‐reactive substances. The activities of the antioxidant enzymes catalase and superoxide dismutase were significantly increased after chronic proline administration, while glutathione (GSH) peroxidase activity, dichlorofluorescin oxidation, GSH, sulfhydryl, and carbonyl content remained unaltered. Histological analyses of the liver revealed that proline treatment induced changes of the hepatic microarchitecture and increased the number of inflammatory cells and the glycogen content. Biochemical determination also demonstrated an increase in glycogen concentration, as well as a higher synthesis of glycogen in liver of hyperprolinemic rats. Regarding to hepatic metabolism, it was observed an increase on glucose oxidation and a decrease on lipid synthesis from glucose. However, hepatic lipid content and serum glucose levels were not changed. Proline administration did not alter the aminotransferases activities and serum markers of hepatic injury. Our findings suggest that hyperprolinemia alters the liver homeostasis possibly by induction of a mild degree of oxidative stress and metabolic changes. The hepatic alterations caused by proline probably do not implicate in substantial hepatic tissue damage, but rather demonstrate a process of adaptation of this tissue to oxidative stress. However, the biological significance of these findings requires additional investigation. J. Cell. Biochem. 113: 174–183, 2012. © 2011 Wiley Periodicals, Inc.
High Glucose‐induced repression of RAR/RXR in cardiomyocytes is mediated through oxidative stress/JNK signaling
Authors: Singh Amar B. , Guleria Rakeshwar S. , Nizamutdinova Irina T. , Baker Kenneth M. , Pan Jing
Published: September 2011

The biological actions of retinoids are mediated by nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs). We have recently reported that decreased expression of RARα and RXRα has an important role in high glucose (HG)‐induced cardiomyocyte apoptosis. However, the regulatory mechanisms of HG effects on RARα and RXRα remain unclear. Using neonatal cardiomyocytes, we found that ligand‐induced promoter activity of RAR and RXR was significantly suppressed by HG. HG promoted protein destabilization and serine‐phosphorylation of RARα and RXRα. Proteasome inhibitor MG132 blocked the inhibitory effect of HG on RARα and RXRα. Inhibition of intracellular reactive oxidative species (ROS) abolished the HG effect. In contrast, H2O2 stimulation suppressed the expression and ligand‐induced promoter activity of RARα and RXRα. HG promoted phosphorylation of ERK1/2, JNK and p38 MAP kinases, which was abrogated by an ROS inhibitor. Inhibition of JNK, but not ERK and p38 activity, reversed HG effects on RARα and RXRα. Activation of JNK by over expressing MKK7 and MEKK1, resulted in significant downregulation of RARα and RXRα. Ligand‐induced promoter activity of RARα and RXRα was also suppressed by overexpression of MEKK1. HG‐induced cardiomyocyte apoptosis was potentiated by activation of JNK, and prevented by all‐trans retinoic acid and inhibition of JNK. Silencing the expression of RARα and RXRα activated the JNK pathway. In conclusion, HG‐induced oxidative stress and activation of the JNK pathway negatively regulated expression/activation of RAR and RXR. The impaired RAR/RXR signaling and oxidative stress/JNK pathway forms a vicious circle, which significantly contributes to hyperglycemia induced cardiomyocyte apoptosis. J. Cell. Physiol. 227: 2632–2644, 2012. © 2011 Wiley Periodicals, Inc.
Thyroid cysts treated with ethanol ablation can mimic malignancy during sonographic follow‐up
Authors: Park Noh Hyuck , Kim Dong Wook , Park Hee Jin , Lee Eun Ja , Park Ji Sung , Park Sung Il , Bae Jong Myon , Lee Jun Hwa
Published: September 2011

Purpose.

We aimed to assess long‐term ultrasound (US) findings after US‐guided percutaneous ethanol ablation (EA) in benign thyroid cysts and predominantly cystic thyroid nodules.

Methods.

Forty patients with thyroid cysts (n = 14) and predominantly cystic thyroid nodules (n = 26) underwent long‐term US follow‐up (range, 12–36 months; mean, 18.2 months) after EA. US images of 40 post‐EA nodules were retrospectively investigated to study the reduction in nodule volume and detailed US appearance.

Results.

On follow‐up US, post‐EA nodules showed the following features: Marked hypoechogenicity (n = 28), spiculated margin (n = 7), microcalcifications (n = 6), taller‐than‐wide shape (n = 2), centrally predominant vascularity (n = 3), no vascularity (n = 31), mixed vascularity (n = 3), and peripheral vascularity (n = 3). Post‐EA nodules were diagnosed by US as benign (n = 3), probably benign (n = 2), borderline (n = 5), possibly malignant (n = 20), and malignant (n = 10). No statistical difference in the incidence of malignant US findings was observed between thyroid cysts and predominantly cystic thyroid nodules (p > 0.05, Fisher's exact test).

Conclusions.

Long‐term follow‐up US after successful EA of benign thyroid cysts and predominantly cystic thyroid nodules revealed a high incidence of findings that are usually associated with malignancy. Recognizing these consequences of the procedure would help avoid unnecessary FNA on post‐EA nodules. © 2011 Wiley Periodicals, Inc. J Clin Ultrasound, 2011;
Impact of production practices on physicochemical properties of rice grain quality
Authors: Bryant Rolfe J , Anders Merle , McClung Anna
Published: September 2011

BACKGROUND: Rice growers are interested in new technologies that can reduce input costs while maintaining high field yields and grain quality. The bed‐and‐furrow (BF) water management system benefits farmers through decreased water usage, labor, and fuel as compared to standard flood management. Fertilizer inputs can be reduced by producing rice in rotation with soybeans, a nitrogen‐fixing crop, and with the use of slow‐release fertilizers that reduce nitrogen volatilization and run‐off. However, the influence of these cultural management practices on rice physicochemical properties is unknown. Our objective was to evaluate the influence of nitrogen fertilizer source, water management system, and crop rotation on rice grain quality.

RESULTS: Grain protein concentration was lower in a continuous rice production system than in a rice–soybean rotation. Neither amylose content nor gelatinization temperature was altered by fertilizer source, crop rotation, or water management. BF water management decreased peak and breakdown viscosities relative to a flooded system. Peak and final paste viscosities were decreased by all fertilizer sources, whereas, crop rotation had no influence on the Rapid Visco Analyser profile.

CONCLUSION: Sustainable production systems that decrease water use and utilize crop rotations and slow‐release fertilizers have no major impact on rice physicochemical properties. Published 2011 by John Wiley & Sons, Ltd.
Bergman Cyclization in Polymer Chemistry and Material Science
Authors: Xiao Yuli , Hu Aiguo
Published: September 2011

Bergman cyclization of enediynes, regarded as a promising strategy for anticancer drugs, now finds its own niche in the area of polymer chemistry and material science. The highly reactive aromatic diradicals generated from Bergman cyclization can undergo polymerization acting as either monomers or initiators of other vinyl monomers. The former, namely homopolymerization, leads to polyphenylenes and polynaphthalenes with excellent thermal stability, good solubility, and processability. The many remarkable properties of these aromatic polymers have further endowed them to be manufactured into carbon‐rich materials, e.g., glassy carbons and carbon nanotubes. Whereas used as initiators, enediynes provide a novel resource for high molecular weight polymers with narrow polydispersities. The aromatic diradicals are also useful for introducing oligomers or polymers onto pristine carbonous nanomaterials, such as carbon nano‐onions and carbon nanotubes, to improve their dispersibility in organic solvents and polymer solutions.

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Down‐regulation of connexin43 expression reveals the involvement of caveolin‐1 containing lipid rafts in human U251 glioblastoma cell invasion
Authors: Strale Pierre‐Olivier , Clarhaut Jonathan , Lamiche Coralie , Cronier Laurent , Mesnil Marc , Defamie Norah
Published: September 2011

Glioblastoma cells are characterized by high proliferation and invasive capacities. Tumor development has been associated with a decrease of gap‐junctional intercellular communication, but the concrete involvement of gap junction proteins, connexins, remains elusive since they are also suspected to promote cell invasion. In order to better understand how connexins control the glioma cell phenotype, we studied the consequences of inhibiting the intrinsic expression of the major astrocytic connexin, Connexin43, in human U251 glioblastoma cells by the shRNA strategy. The induced down‐regulation of Cx43 expression has various effects on the U251 cells such as increased clonogenicity, angiogenesis and decreased adhesion on specific extracellular matrix proteins. We demonstrate that the invasion capacity measured in vitro and ex vivo correlates with Cx43 expression level. For the first time in a cancer cell context, our work demonstrates that Cx43 cofractionates, colocalizes and coimmunoprecipitates with a lipid raft marker, caveolin‐1 and that this interaction is inversely correlated to the level of Cx43. This localization of Cx43 in these lipid raft microdomains regulates both homo‐ and heterocellular gap junctional communications (respectively between U251 cells, or between U251 cells and astrocytes). Moreover, the adhesive and invasive capacities are not dependent, in our model, on Cav‐1 expression level. Our results tend to show that heterocellular gap junctional communication between cancer and stroma cells may affect the behavior of the tumor cells. Altogether, our data demonstrate that Cx43 controls the tumor phenotype of glioblastoma U251 cells and in particular, invasion capacity, through its localization in lipid rafts containing Cav‐1. © 2011 Wiley Periodicals, Inc.
Dietary lipids and their oxidized products in Alzheimer's disease
Authors: Corsinovi Laura , Biasi Fiorella , Poli Giuseppe , Leonarduzzi Gabriella , Isaia Gianluca
Published: September 2011

Alzheimer's disease (AD) is the commonest form of dementia in the elderly, characterized by memory dysfunction, loss of lexical access, spatial and temporal disorientation, and impaired judgment. A growing body of scientific literature addresses the implication of dietary habits in the pathogenesis of AD. This review reports recent findings concerning the modulation of AD development by dietary lipids, in animals and humans, focusing on the pathogenetic role of lipid oxidation products. Oxidative breakdown products of ω‐6 polyunsaturated fatty acids (ω‐6 PUFAs), and cholesterol oxidation products (oxysterols), might play a role in favoring β‐amyloid deposition, a hallmark of AD's onset and progression. Conversely, ω‐3 PUFAs appear to contribute to preventing and treating AD. However, high concentrations of ω‐3 PUFAs can also produce oxidized derivatives reacting with important functions of nervous cells. Thus, altered balances between cholesterol and oxysterols, and between ω‐3 and ω‐6 PUFAs must be considered in AD's pathophysiology. The use of a diet with an appropriate ω‐3/ω‐6 PUFA ratio, rich in healthy oils, fish and antioxidants, such as flavonoids, but low in cholesterol‐containing foods, can be a beneficial component in the clinical strategies of prevention of AD.
An adaptive edge element method and its convergence for a Saddle‐Point problem from magnetostatics
Authors: Chen Junqing , Xu Yifeng , Zou Jun
Published: September 2011

Reliable and efficient a posteriori error estimates are derived for the edge element discretization of a saddle‐point Maxwell's system. By means of the error estimates, an adaptive edge element method is proposed and its convergence is rigorously demonstrated. The algorithm uses a marking strategy based only on the error indicators, without the commonly used information on local oscillations and the refinement to meet the standard interior node property. Some new ingredients in the analysis include a novel quasi‐orthogonality and a new inf‐sup inequality associated with an appropriately chosen norm. It is shown that the algorithm is a contraction for the sum of the energy error plus the error indicators after each refinement step. Numerical experiments are presented to show the robustness and effectiveness of the proposed adaptive algorithm. © 2011 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2012
Factors Associated With Parental Perception of Child Vulnerability 12 Months After Abnormal Newborn Screening Results
Authors: Tluczek Audrey , McKechnie Anne Chevalier , Brown Roger L.
Published: September 2011

We identified factors associated with elevated parental perceptions of child vulnerability (PPCV) 12 months after newborn screening (NBS) of 136 children: healthy, normal results (H, n = 37), cystic fibrosis carriers (CF‐C, n = 40), congenital hypothyroidism (CH, n = 36), and cystic fibrosis (CF, n = 23). Controlling for infant and parent characteristics, mixed logit structural equation modeling showed direct paths to elevated PPCV included parent female sex, CF diagnosis, and high documented illness frequency. PPCV was positively associated with maternal parenting stress. Infants with CF and CF carriers had significantly more documented illness frequency than H group infants. The CH group did not differ significantly from the H group and had no paths to PPCV. Unexpectedly high documented illness frequency among infants who are CF carriers warrants further investigation. © 2011 Wiley Periodicals, Inc. Res Nurs Health 34:389–400, 2011
Intracoronary delivery of DNAzymes targeting human EGR‐1 reduces infarct size following myocardial ischaemia reperfusion
Authors: Bhindi Ravinay , Fahmy Roger G , McMahon Aisling C , Khachigian Levon M , Lowe Harry C
Published: September 2011

Despite improvements in treatment, myocardial infarction (MI) remains an important cause of morbidity and mortality. Inflammation arising from ischaemic and reperfusion injury is a key mechanism which underpins myocardial damage and impairment of cardiac function. Early growth response‐1 (Egr‐1) is an early immediate gene and a master regulator that has been implicated in the pathogenesis of ischaemia‐reperfusion (IR) injury. This study sought to examine the effect of selective inhibition of Egr‐1 using catalytic deoxyribonucleic acid molecules (DNAzymes, DZs) delivered via the clinically relevant coronary route in a large animal model of myocardial IR. It was hypothesized that Egr‐1 inhibition with intracoronary DZ would reduce infarction size by modulating its downstream effector molecules. Egr‐1 DZs inhibited the adherence of THP‐1 monocytes to IL‐1β‐activated endothelial cells in vitro and retained its catalytic activity up to 225 min after in vivo administration. In a porcine model of myocardial IR (45 min ischaemia/3 h reperfusion), DZ was taken up in the cytoplasm and nuclei of cardiomyocytes and endothelial cells in the myocardium after intracoronary delivery. Egr‐1 DZs reduced infarct size and improved cardiac functional recovery following intracoronary delivery at the initiation of IR in this large animal model of MI. This was associated with inhibition of pro‐inflammatory Egr‐1 and ICAM‐1 expression, and the reduced expression of TNF‐α, PAI‐1, TF, and myocardial MPO activity in tissue derived from the border zone of the infarct. Taken together, these data suggest that strategies targeting Egr‐1 via the intracoronary route after IR injury in pigs have potential therapeutic implications in human MI. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Crosslink network evolution of nature rubber/zinc dimethacrylate composite during peroxide vulcanization
Authors: Chen Yukun , Xu Chuanhui
Published: September 2011

In this article, we investigated the evolution of the crosslink networks in nature rubber (NR) which is filled with in situ zinc dimethacrylate (ZDMA) during vulcanization. The results revealed that a primary network dominated by the ionic bond could be formed in the first 1 min, while the backbone of the covalent crosslink network was not formed. The ionic crosslinks, cooperating with some other physical crosslinks and some primary covalent crosslink points, play an important role in supporting the crosslink backbone of the composite in this period. This primary network was strong enough to bear the force exerted by the moving die of the Rheometer and to enable the composite that do not dissolve in toluene. After that, both the covalent crosslinking of NR molecules and polymerization of ZDMA react rapidly to give a birth to the fundamental network of the composites. Fourier transform infrared spectroscopy and differential scanning calorimeter were also used to investigate the curing reaction of the NR/ZDMA compounds. After ZDMA reaching a considerable conversion, the substantial covalent crosslinking reaction starts to be initiated. These results support the primary network dominated by the ionic bond formed in the first 1 min. POLYM. COMPOS., 2011. © 2011 Society of Plastics Engineers
Pattern of occurrence and occupancy of carbonylation sites in proteins
Authors: Rao R. Shyama Prasad , Møller Ian Max
Published: September 2011

Proteins are targets for modification by reactive oxygen species, and carbonylation is an important irreversible modification that increases during oxidative stress. While information on protein carbonylation is accumulating, its pattern is not yet understood. We have made a meta‐analysis of the available literature data (456 carbonylation sites on 208 proteins) to appreciate the nature of carbonylation sites in proteins. Of the carbonylated (Arg, Lys, Pro, and Thr – RKPT) amino acids, Lys is the most abundant, whereas Pro is the most susceptible and Thr is the least susceptible. The incidence of carbonylation is lower in the N‐terminal part of the protein primary sequence. Although a significantly higher number of carbonylated sites occur in Arg‐, Lys‐, Pro‐ and Thr‐rich regions of proteins, the hydropathy environment of carbonylated sites is not significantly different from potential carbonylation sites. Comparison of metal‐catalyzed oxidation of two closely related proteins indicates that this type of carbonylation might not be very specific in proteins. Interestingly, carbonylated sites show a very strong tendency to cluster together in the protein primary sequence hinting at some sort of discerning mechanism. While some attributes of protein carbonylation appear to be random, further investigations are warranted to appreciate the deterministic nature of protein carbonylation sites.
Virus‐induced dilated cardiomyopathy is characterized by increased levels of fibrotic extracellular matrix proteins and reduced amounts of energy‐producing enzymes
Authors: Nishtala Krishnatej , Phong Truong Q. , Steil Leif , Sauter Martina , Salazar Manuela G. , Kandolf Reinhard , Kroemer Heyo K. , Felix Stephan B. , Völker Uwe , Klingel Karin , Hammer Elke
Published: September 2011

The most relevant clinical phenotype resulting from chronic enteroviral myocarditis is dilated cardiomyopathy (DCM). Mice of the susceptible mouse strain A.BY/SnJ mimick well human DCM since they develop as a consequence of persistent infection and chronic inflammation a dilation of the heart ventricle several weeks after coxsackievirus B3 (CVB3) infection. Therefore, this model is well suited for the analysis of changes in the heart proteome associated with DCM. Here, we present a proteomic survey of the dilated hearts based on differential fluorescence gel electrophoresis and liquid chromatography–mass spectrometric centered methods in comparison to age‐matched non‐infected hearts. In total, 101 distinct proteins, which belong to categories immunity and defense, cell structure and associated proteins, energy metabolism and protein metabolism/modification differed in their levels in both groups. Levels of proteins involved in fatty acid metabolism and electron transport chain were found to be significantly reduced in infected mice suggesting a decrease in energy production in CVB3‐induced DCM. Furthermore, proteins associated with muscle contraction (MLRV, MLRc2, MYH6, MyBPC3), were present in significantly altered amounts in infected mice. A significant increase in the level of extracellular matrix proteins in the dilated hearts indicates cardiac remodeling due to fibrosis.
Luminescence and scintillation of Ce3+‐doped oxide glass with high Gd2O3 concentration
Authors: Chewpraditkul W. , He X. , Chen D. , Shen Y. , Sheng Q. , Yu B. , Nikl M. , Kucerkova R. , Beitlerova A. , Wanarak C. , Phunpueok A.
Published: September 2011

Ce3+‐doped oxide glass with high Gd2O3 (30 mol%) concentration was prepared as a scintillating glass under CO reducing atmosphere. A dominant emission band of the Ce3+ 5d → 4f transition peaking around 400 nm was observed in the photo‐ and radioluminescence (PL, RL) spectra. PL decay was governed by a few tens of nanoseconds decay time. The integral scintillation efficiency of about 30% of the Bi4Ge3O12 scintillator was observed as well. It exhibits a light yield of about 910 photons/MeV with an energy resolution of 18.3% (FWHM) in the pulse height spectrum of 662 keV γ‐rays from a 137Cs source.