bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microglial regulation of cholinergic differentiation in the basal forebrain
Authors: Jonakait G. Miller , Pratt Lorelei , Acevedo Giselles , Ni Li 
Published: September 2011

AbstractBecause 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

AbstractTwo 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

AbstractThe 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

AbstractLoss 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

ObjectiveAlzheimer'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).MethodsTwenty‐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.ResultsStatistical 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.ConclusionsApathy 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

SUMMARYAlthough 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

AbstractMany 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

AbstractThe 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

AbstractThis 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

AbstractDrugs 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

AbstractmicroRNA (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

Abstract
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

AbstractThe 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.