bluuebunny/crossref_metadata_2025 huggingface dataset:
Sry, more than testis determination?
Authors: Turner Monte E. , Ely Daniel , Prokop Jeremy , Milsted Amy
Published: June 2011

The Sry locus on the mammalian Y chromosome is the developmental switch responsible for testis determination. Inconsistent with this important function, the Sry locus is transcribed in adult males at times and in tissues not involved with testis determination. Sry is expressed in multiple tissues of the peripheral and central nervous system. Sry is derived from Sox3 and is similar to other SOXB family loci. The SOXB loci are responsible for nervous system development. Sry has been demonstrated to modulate the catecholamine pathway, so it should have functional consequences in the central and peripheral nervous system. The nervous system expression and potential function are consistent with Sry as a SOXB family member. In mammals, Sox3 is X-linked and undergoes dosage compensation in females. The expression of Sry in adult males allows for a type of sexual differentiation independent of circulating gonadal hormones. A quantitative difference in Sox3 plus Sry expression in males vs. females could drive changes in the transcriptome of these cells, differentiating male and female cells. Sry expression and its transcriptional effects should be considered when investigating sexual dimorphic phenotypes.
Adenosine A2areceptors and O2sensing in development
Authors: Koos Brian J.
Published: June 2011

Reduced mitochondrial oxidative phosphorylation, via activation of adenylate kinase and the resulting exponential rise in the cellular AMP/ATP ratio, appears to be a critical factor underlying O2sensing in many chemoreceptive tissues in mammals. The elevated AMP/ATP ratio, in turn, activates key enzymes that are involved in physiologic adjustments that tend to balance ATP supply and demand. An example is the conversion of AMP to adenosine via 5′-nucleotidase and the resulting activation of adenosine A2Areceptors, which are involved in acute oxygen sensing by both carotid bodies and the brain. In fetal sheep, A2Areceptors associated with carotid bodies trigger hypoxic cardiovascular chemoreflexes, while central A2Areceptors mediate hypoxic inhibition of breathing and rapid eye movements. A2Areceptors are also involved in hypoxic regulation of fetal endocrine systems, metabolism, and vascular tone. In developing lambs, A2Areceptors play virtually no role in O2sensing by the carotid bodies, but brain A2Areceptors remain critically involved in the roll-off ventilatory response to hypoxia. In adult mammals, A2Areceptors have been implicated in O2sensing by carotid glomus cells, while central A2Areceptors likely blunt hypoxic hyperventilation. In conclusion, A2Areceptors are crucially involved in the transduction mechanisms of O2sensing in fetal carotid bodies and brains. Postnatally, central A2Areceptors remain key mediators of hypoxic respiratory depression, but they are less critical for O2sensing in carotid chemoreceptors, particularly in developing lambs.
Cortical activation and lamina terminalis functional connectivity during thirst and drinking in humans
Authors: Farrell M. J. , Bowala T. K. , Gavrilescu M. , Phillips P. A. , McKinley M. J. , McAllen R. M. , Denton D. A. , Egan G. F.
Published: June 2011

The pattern of regional brain activation in humans during thirst associated with dehydration, increased blood osmolality, and decreased blood volume is not known. Furthermore, there is little information available about associations between activation in osmoreceptive brain regions such as the organum vasculosum of the lamina terminalis and the brain regions implicated in thirst and its satiation in humans. With the objective of investigating the neuroanatomical correlates of dehydration and activation in the ventral lamina terminalis, this study involved exercise-induced sweating in 15 people and measures of regional cerebral blood flow (rCBF) using a functional magnetic resonance imaging technique called pulsed arterial spin labeling. Regional brain activations during dehydration, thirst, and postdrinking were consistent with the network previously identified during systemic hypertonic infusions, thus providing further evidence that the network is involved in monitoring body fluid and the experience of thirst. rCBF measurements in the ventral lamina terminalis were correlated with whole brain rCBF measures to identify regions that correlated with the osmoreceptive region. Regions implicated in the experience of thirst were identified including cingulate cortex, prefrontal cortex, striatum, parahippocampus, and cerebellum. Furthermore, the correlation of rCBF between the ventral lamina terminalis and the cingulate cortex and insula was different for the states of thirst and recent drinking, suggesting that functional connectivity of the ventral lamina terminalis is a dynamic process influenced by hydration status and ingestive behavior.
Mre11 is expressed in mammalian mitochondria where it binds to mitochondrial DNA
Authors: Dmitrieva Natalia I. , Malide Daniela , Burg Maurice B.
Published: June 2011

Mre11 is a critical participant in upkeep of nuclear DNA, its repair, replication, meiosis, and maintenance of telomeres. The upkeep of mitochondrial DNA (mtDNA) is less well characterized, and whether Mre11 participates has been unknown. We previously found that high NaCl causes some of the Mre11 to leave the nucleus, but we did not then attempt to localize it within the cytoplasm. In the present studies, we find Mre11 in mitochondria isolated from primary renal cells and show that the amount of Mre11 in mitochondria increases with elevation of extracellular NaCl. We confirm the presence of Mre11 in the mitochondria of cells by confocal microscopy and show that some of the Mre11 colocalizes with mtDNA. Furthermore, crosslinking of Mre11 to DNA followed by Mre11 immunoprecipitation directly demonstrates that some Mre11 binds to mtDNA. Abundant Mre11 is also present in tissue sections from normal mouse kidneys, colocalized with mitochondria of proximal tubule and thick ascending limb cells. To explore whether distribution of Mre11 changes with cell differentiation, we used an experimental model of tubule formation by culturing primary kidney cells in Matrigel matrix. In nondifferentiated cells, Mre11 is mostly in the nucleus, but it becomes mostly cytoplasmic upon cell differentiation. We conclude that Mre11 is present in mitochondria where it binds to mtDNA and that the amount in mitochondria varies depending on cellular stress and differentiation. Our results suggest a role for Mre11 in the maintenance of genome integrity in mitochondria in addition to its previously known role in maintenance of nuclear DNA.
Anti-VEGF antibody treatment accelerates polycystic kidney disease
Authors: Raina Shagun , Honer Michael , Krämer Stefanie D. , Liu Yang , Wang Xueqi , Segerer Stephan , Wüthrich Rudolf P. , Serra Andreas L.
Published: June 2011

Polycystic kidney growth implies expansion of the vasculature, suggesting that vascular endothelial growth factor (VEGF)-dependent processes play a critical role and that VEGF is a putative therapeutic target. Whether an anti-VEGF antibody improves renal cystic disease has not been determined. We administrated 5 mg/kg B20.4.1, an anti-VEGF-A antibody, or vehicle intraperitoneally twice weekly to 4-wk-old male normal (+/+) and cystic (Cy/+) Han:SPRD rats for 6 wk. Renal function, urinary protein excretion, organ/body weight ratios, cyst volume, tubular epithelial cell (TEC) proliferation, renal VEGF, hypoxia-inducible factor (HIF)-1α and -2α expression, renal histology, and kidney hypoxia visualized by [18F]fluoromisonidazole positron emission tomography were assessed. The treated compared with untreated +/+ rats had lower TEC proliferation rates, whereas Cy/+ rats receiving B20.4.1 displayed an increased proximal TEC proliferation rate, causing enhanced cyst and kidney growth. The +/+ and Cy/+ rats receiving B20.4.1 had severe renal failure and extensive glomerular damage. Proteinuria, which was highest in anti-VEGF-treated Cy/+ and lowest in untreated normal littermates, was positively correlated with renal HIF-1α and negatively correlated with VEGF expression. The untreated Cy/+ vs. +/+ rats had higher overall [18F]fluoromisonidazole uptake. The +/+ rats receiving B20.4.1 vs. untreated had increased [18F]fluoromisonidazole uptake, whereas the uptake was unchanged among treated vs. untreated Cy/+ animals. In conclusion, B20.4.1 caused an exaggerated cystic response of the proximal tubules in cystic rats and severe kidney injury that was associated with low renal VEGF and high HIF-1α levels. Anti-VEGF drug therapy may therefore not be a treatment option for polycystic kidney disease.
Activity of the Ste20-like kinase, SLK, is enhanced by homodimerization
Authors: Delarosa Sierra , Guillemette Julie , Papillon Joan , Han Ying-Shan , Kristof Arnold S. , Cybulsky Andrey V.
Published: June 2011

The expression and activation of the Ste20-like kinase, SLK, is increased during renal development and recovery from ischemic acute renal failure. SLK promotes apoptosis, and during renal injury and repair, transcriptional induction or posttranscriptional control of SLK may, therefore, regulate cell survival. SLK contains protein interaction (coiled-coil) domains, suggesting that posttranslational homodimerization may also modulate SLK activity. We therefore expressed coiled-coil regions in the C-terminal domain of SLK as fusion proteins and demonstrated their homodimerization. By gel-filtration chromatography, endogenous and heterologously expressed SLK were detected in a macromolecular protein complex. To test the role of homodimerization in kinase activation, we constructed a fusion protein consisting of the SLK catalytic domain (amino acids 1–373) and a modified FK506 binding protein, Fv (Fv-SLK 1–373). Addition of AP20187 (an analog of FK506) enhanced the homodimerization of Fv-SLK 1–373. In an in vitro kinase assay, the dimeric Fv-SLK 1–373 displayed greater kinase activity than the monomeric form. In cells expressing Fv-SLK 1–373, homodimerization increased activation-specific phosphorylation of the proapoptotic kinases, c-Jun N-terminal kinase and p38 kinase. Compared with the monomer, dimeric Fv-SLK 1–373 enhanced the activation of a Bax promoter-luciferase reporter. Finally, expression of Fv-SLK 1–373 induced apoptosis, and the effect was increased by homodimerization. Thus the activity, downstream signaling, and functional effects of SLK are enhanced by dimerization of the kinase domain.
Galectin-7 modulates the length of the primary cilia and wound repair in polarized kidney epithelial cells
Authors: Rondanino Christine , Poland Paul A. , Kinlough Carol L. , Li Hui , Rbaibi Youssef , Myerburg Michael M. , Al-bataineh Mohammad M. , Kashlan Ossama B. , Pastor-Soler Nuria M. , Hallows Kenneth R. , Weisz Ora A. , Apodaca Gerard , Hughey Rebecca P.
Published: June 2011

Galectins (Gal) are β-galactoside-binding proteins that function in epithelial development and homeostasis. An overlapping role for Gal-3 and Gal-7 in wound repair was reported in stratified epithelia. Although Gal-7 was thought absent in simple epithelia, it was reported in a proteomic analysis of cilia isolated from cultured human airway, and we recently identified Gal-7 transcripts in Madin-Darby canine kidney (MDCK) cells (Poland PA, Rondanino C, Kinlough CL, Heimburg-Molinaro J, Arthur CM, Stowell SR, Smith DF, Hughey RP. J Biol Chem 286: 6780–6790, 2011). We now report that Gal-7 is localized exclusively on the primary cilium of MDCK, LLC-PK1(pig kidney), and mpkCCDc14(mouse kidney) cells as well as on cilia in the rat renal proximal tubule. Gal-7 is also present on most cilia of multiciliated cells in human airway epithelia primary cultures. Interestingly, exogenous glutathione S-transferase (GST)-Gal-7 bound the MDCK apical plasma membrane as well as the cilium, while the lectin Ulex europeaus agglutinin, with glycan preferences similar to Gal-7, bound the basolateral plasma membrane as well as the cilium. In pull-down assays, β1-integrin isolated from either the basolateral or apical/cilia membranes of MDCK cells was similarly bound by GST-Gal-7. Selective localization of Gal-7 to cilia despite the presence of binding sites on all cell surfaces suggests that intracellular Gal-7 is specifically delivered to cilia rather than simply binding to surface glycoconjugates after generalized secretion. Moreover, depletion of Gal-7 using tetracycline-induced short-hairpin RNA in mpkCCDc14cells significantly reduced cilia length and slowed wound healing in a scratch assay. We conclude that Gal-7 is selectively targeted to cilia and plays a key role in surface stabilization of glycoconjugates responsible for integrating cilia function with epithelial repair.
ERK pathway mediates P2X7 expression and cell death in renal interstitial fibroblasts exposed to necrotic renal epithelial cells
Authors: Ponnusamy Murugavel , Liu Na , Gong Rujun , Yan Haidong , Zhuang Shougang
Published: June 2011

We recently reported that necrotic renal proximal epithelial cells (RPTC) stimulate the expression of P2X7 receptor in renal fibroblasts and that P2X7 receptor mediates deleterious epithelial-fibroblast cross talk. The present study was carried out to investigate the signaling mechanism of necrotic RPTC-induced P2X7 expression in cultured renal interstitial fibroblasts (NRK-49F). Exposure of NRK-49F to necrotic RPTC supernatant (RPTC-Sup) induced a time- and dose-dependent phosphorylation of several signaling pathways including extracellular signal-regulated kinases (ERK1/2), p38, c-Jun N-terminal kinases (JNKs), and AKT in NRK-49F. Pharmacological inhibition of ERK1/2, but not p38, JNK, and AKT pathways, blocked RPTC-Sup-induced P2X7 expression and renal interstitial fibroblast death. Knockdown of ERK1/2 or MEK1, a direct upstream activator of ERK1/2, also reduced RPTC-Sup-induced P2X7 expression and cell death of renal fibroblasts. Conversely, overexpression of MEK1 enhanced these responses. Upon necrotic RPTC exposure, phosphorylation of Elk1, a transcriptional factor targeted by ERK1/2, was increased in NRK-49F, and knockdown of Elk1 by siRNA remarkably reduced RPTC-Sup-induced P2X7 expression as well as renal fibroblast death. Furthermore, silencing of MEK1 inhibited Elk1 phosphorylation in response to necrotic RPTC, whereas overexpression of MEK1 increased Elk1 phosphorylation. Taken together, these data reveal that necrotic RPTC induces P2X7 expression in renal fibroblasts through activation of the MEK1-ERK1/2-Elk1 signaling pathway.
Therapeutic potential of DCB-SLE1, an extract of a mixture of Chinese medicinal herbs, for severe lupus nephritis
Authors: Tsai Pei-Yi , Ka Shuk-Man , Chang Jia-Ming , Chang Wen-Liang , Huang Yuan-Jen , Hung Le-Mei , Jheng Huei-Lin , Wu Rey-Yuh , Chen Ann
Published: June 2011

The pathogenesis of lupus nephritis is mainly attributable to a complex interaction between the innate and adaptive immune systems, including T and B cell function abnormalities. In addition to autoantibody production and immune complex deposition, Th1 and Th17 cytokines may play key roles in the development and progression of lupus nephritis. Acute onset of severe lupus nephritis remains a challenge in terms of prevention and treatment. In the present study, we evaluated the therapeutic effects of DCB-SLE1, an extract of a mixture of four traditional Chinese medicinal herbs ( Atractylodis macrocephalae Rhizoma, Eucommiae cortex , Lonicerae caulis , and Hedyotidis diffusae Herba), on an accelerated severe lupus nephritis model, characterized by acute onset of proteinuria, azotemia, autoantibody production, and development of severe nephritis, induced by twice weekly injection of New Zealand black/white F1 mice with Salmonella -type lipopolysaccharide. DCB-SLE1 was administered daily by gavage starting 2 days after the first dose of induction of lipopolysaccharide, and the mice were euthanized at week 1 or week 5. The results showed that DCB-SLE1 significantly ameliorated the hematuria, proteinuria, renal dysfunction, and severe renal lesions by 1) suppression of B cell activation and decreased autoantibody production; 2) negative regulation of T cell activation/proliferation and natural killer cell activity; 3) suppression of IL-18, IL-6, and IL-17 production and blocking of NF-κB activation in the kidney; and 4) prevention of lymphoid and renal apoptosis. These results show that DCB-SLE1 can protect the kidney from autoimmune response-mediated acute and severe damage through systemic immune modulation and anti-inflammation pathways.
Changes in action potential features during focal seizure discharges in the entorhinal cortex of the in vitro isolated guinea pig brain
Authors: Trombin Federica , Gnatkovsky Vadym , de Curtis Marco
Published: June 2011

Temporal lobe seizures in humans correlate with stereotyped electrophysiological patterns that can be reproduced in animal models to study the cellular and network changes responsible for ictogenesis. Seizure-like discharges that mimic seizure patterns in humans were induced in the entorhinal cortex of the in vitro isolated guinea pig brain by 3-min arterial applications of the GABAA receptor antagonist bicuculline. The onset of seizure is characterized by a paradoxical interruption of firing for several seconds in principal neurons coupled with both enhanced interneuronal firing and increased extracellular potassium ( Gnatkovsky et al. 2008 ). The evolution of action potential features from firing break to excessive and synchronous activity associated with the progression of seizure itself is analyzed here. We utilized phase plot analysis to characterize action potential features of entorhinal cortex neurons in different phases of a seizure. Compared with preictal action potentials, resumed spikes in layer II–III neurons ( n = 17) during the early phase of the seizure-like discharge displayed 1) depolarized threshold, 2) lower peak amplitude, 3) depolarized voltage of repolarization and 4) decelerated depolarizing phase, and 5) spike doublettes. Action potentials in deep-layer principal cells ( n = 8) during seizure did not show the marked feature changes observed in superficial layer neurons. Action potential reappearance correlated with an increase in extracellular potassium. High-threshold, slow-action potentials similar to those observed in the irregular firing phase of a seizure were reproduced in layer II–III neurons by direct cortical application of a highly concentrated potassium solution (12–24 mM). We propose that the generation of possibly nonsomatic action potentials by increased extracellular potassium represents a crucial step toward reestablish firing after an initial depression in an acute model of temporal lobe seizures. Resumed firing reengages principal neurons into seizure discharge and promotes the transition toward the synchronized burst firing that characterizes the late phase of a seizure.
Dopamine-induced oscillations of the pyloric pacemaker neuron rely on release of calcium from intracellular stores
Authors: Kadiri Lolahon R. , Kwan Alex C. , Webb Watt W. , Harris-Warrick Ronald M.
Published: June 2011

Endogenously bursting neurons play central roles in many aspects of nervous system function, ranging from motor control to perception. The properties and bursting patterns generated by these neurons are subject to neuromodulation, which can alter cycle frequency and amplitude by modifying the properties of the neuron's ionic currents. In the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus, the anterior burster (AB) neuron is a conditional oscillator in the presence of dopamine (DA) and other neuromodulators and serves as the pacemaker to drive rhythmic output from the pyloric network. We analyzed the mechanisms by which DA evokes bursting in the AB neuron. Previous work showed that DA-evoked bursting is critically dependent on external calcium (Harris-Warrick RM, Flamm RE. J Neurosci 7: 2113–2128, 1987). Using two-photon microscopy and calcium imaging, we show that DA evokes the release of calcium from intracellular stores well before the emergence of voltage oscillations. When this release from intracellular stores is blocked by antagonists of ryanodine or inositol trisphosphate (IP3) receptor channels, DA fails to evoke AB bursting. We further demonstrate that DA enhances the calcium-activated inward current, ICAN, despite the fact that it significantly reduces voltage-activated calcium currents. This suggests that DA-induced release of calcium from intracellular stores activates ICAN, which provides a depolarizing ramp current that underlies endogenous bursting in the AB neuron.
Object-level visual information gets through the bottleneck of crowding
Authors: Fischer Jason , Whitney David
Published: June 2011

Natural visual scenes are cluttered. In such scenes, many objects in the periphery can be crowded, blocked from identification, simply because of the dense array of clutter. Outside of the fovea, crowding constitutes the fundamental limitation on object recognition and is thought to arise from the limited resolution of the neural mechanisms that select and bind visual features into coherent objects. Thus it is widely believed that in the visual processing stream, a crowded object is reduced to a collection of dismantled features with no surviving holistic properties. Here, we show that this is not so: an entire face can survive crowding and contribute its holistic attributes to the perceived average of the set, despite being blocked from recognition. Our results show that crowding does not dismantle high-level object representations to their component features.
Analyzing “Homotopy Perturbation Method for Solving Fourth‐Order Boundary Value Problem"
Authors: Aslanov Afgan
Published: June 2011

We analyze a previous paper by S. T. Mohyud‐Din and M. A. Noor (2007) and show the mistakes in it. Then, we demonstrate a more efficient method for solving fourth‐order boundary value problems.
Allergic Responses Induced by a Fungal BiopesticideMetarhizium anisopliaeand House Dust Mite Are Compared in a Mouse Model
Authors: Ward Marsha D. W. , Chung Yong Joo , Copeland Lisa B. , Doerfler Donald L.
Published: June 2011

Biopesticides can be effective in controlling their target pest. However, research regarding allergenicity and asthma development is limited. We compared the ability of fungal biopesticideMetarhizium anisopliae(MACA) and house dust mite (HDM) extracts to induce allergic responses in BALB/c mice. The extracts were administered by intratracheal aspiration at doubling doses (2.5–80 g protein) 4X over a four-week period. Three days after the last exposure, serum and bronchoalveolar lavage fluid (BALF) were collected. The extracts' relative allergenicity was evaluated based on response robustness (lowest significant dose response compared to control (0 g)). MACA induced a more robust serum total IgE response than HDM. However, in the antigen-specific IgE assay, a similar dose of both MACA and HDM was required to achieve the same response level. Our data suggest a threshold dose of MACA for allergy induction and thatM. anisopliaemay be similar to HDM in allergy induction potential.
Relativistic Milne-Eddington Type Solutions with a Variable Eddington Factor for Relativistic Spherical Winds
Authors: Fukue Jun
Published: June 2011

Relativistic radiative transfer in a relativistic spherical flow is examined in the fully special relativistic treatment. Under the assumption of a constant flow speed and using a variable (prescribed) Eddington factor, we analytically solve the relativistic moment equations in the comoving frame for several restricted cases, and obtain relativistic Milne-Eddington type solutions. In contrast to the plane-parallel case where the solutions exhibit the exponential behavior on the optical depth, the solutions have power-law forms. In the case of the radiative equilibrium, for example, the radiative flux has a power-law term multiplied by the exponential term. In the case of the local thermodynamic equilibrium with a uniform source function in the comoving frame, the radiative flux has a power-law form on the optical depth. This is because there is an expansion effect (curvature effect) in the spherical wind and the background density decreases as the radius increases.
Toric Methods in F-Theory Model Building
Authors: Knapp Johanna , Kreuzer Maximilian
Published: June 2011

We discuss recent constructions of global F-theory GUT models and explain how to make use of toric geometry to do calculations within this framework. After introducing the basic properties of global F-theory GUTs, we give a self-contained review of toric geometry and introduce all the tools that are necessary to construct and analyze global F-theory models. We will explain how to systematically obtain a large class of compact Calabi-Yau fourfolds which can support F-theory GUTs by using the software package PALP.
Microwave-Assisted Combustion Synthesis of Nano Iron Oxide/Iron-Coated Activated Carbon, Anthracite, Cellulose Fiber, and Silica, with Arsenic Adsorption Studies
Authors: Nadagouda Mallikarjuna N. , Lytle Darren A.
Published: June 2011

Combustion synthesis of iron oxide/iron coated carbons such as activated carbon, anthracite, cellulose fiber, and silica is described. The reactions were carried out in alumina crucibles using a Panasonic kitchen microwave with inverter technology, and the reaction process was completed within a few minutes. The method used no additional fuel and nitrate, which is present in the precursor itself, to drive the reaction. The obtained samples were then characterized with X-ray mapping, scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDS), selected area diffraction pattern (SAED), transmission electron microscopy (TEM), X-ray diffraction (XRD), and inductively coupled plasma (ICP) spectroscopy. The size of the iron oxide/iron nanoparticle-coated activated carbon, anthracite, cellulose fiber, and silica samples were found to be in the nano range (50–400 nm). The iron oxide/iron nanoparticles mostly crystallized into cubic symmetry which was confirmed by SAED. The XRD pattern indicated that iron oxide/iron nano particles existed in four major phases. That is, γ-Fe2O3, α-Fe2O3, Fe3O4, and Fe. These iron-coated activated carbon, anthracite, cellulose fiber, and silica samples were tested for arsenic adsorption through batch experiments, revealing that few samples had significant arsenic adsorption.
Fluorescent Properties of ZnO Nanostructures Fabricated by Hydrothermal Method
Authors: Dong Zhiwei , Han Bing , Qian Shixiong , Chen Deying
Published: June 2011

ZnO nanorods with mean diameter 200 nm on different substrates were fabricated by hydrothermal method. Fluorescent properties of fabricated ZnO nanorods were researched by both linear and nonlinear excitation using femtosecond lasers. The damage threshold of productions on Si substrate irradiated under intense femtosecond pulses was found much higher than that on Zn plate. Raman spectrum was also applied to investigate relative optical properties. The A1L optical mode was found to be important to the fluorescent properties of ZnO materials.
Genetic Variation in an miRNA-1827 Binding Site in MYCL1 Alters Susceptibility to Small-Cell Lung Cancer
Authors: Xiong Fang , Wu Chen , Chang Jiang , Yu Dianke , Xu Binghe , Yuan Peng , Zhai Kan , Xu Jian , Tan Wen , Lin Dongxin
Published: June 2011

Genetic variations in microRNAs (miRNA) that affect control of their target genes may alter individual susceptibilities to cancer. In this study, we took an in silico approach to identify single-nucleotide polymorphisms (SNP) within the 3′-untranslated region (UTR) of miRNA genes deregulated in human small-cell lung cancer (SCLC), and then investigated their associations with SCLC susceptibility in 666 SCLC patients and 758 controls. Odds ratios (OR) were estimated by multivariate logistic regression, and biochemical assays were conducted to investigate SNP functions. We identified 2 SNPs, rs3134615 and rs2291854, which were located in the 3′-UTR of the L-MYC gene MYCL1 and the neuronal development Achaete-Scute Complex homolog ASCL1. Case–control analyses showed that the rs3134615T allele was associated with a significantly increased risk of SCLC, with the OR for carrying the GT or TT genotype being 2.08 (95% confidence interval, 1.39–3.21; P = 0.0004) compared with the GG genotype. In support of the likelihood that these 3′-UTR SNPs may directly affect miRNA-binding sites, reporter gene assays indicated MYCL1 as the target of hsa-miR-1827 and the rs3134615 G>T change resulted in altered regulation of MYCL1 expression. Our findings define a 3′-UTR SNP in the human L-MYC oncogene that may increase susceptibility to SCLC, possibly resulting from attenuated interaction with the miRNA hsa-miR-1827. Cancer Res; 71(15); 5175–81. ©2011 AACR.
MicroRNA Replacement Therapy for miR-145 and miR-33a Is Efficacious in a Model of Colon Carcinoma
Authors: Ibrahim Ahmed Fawzy , Weirauch Ulrike , Thomas Maren , Grünweller Arnold , Hartmann Roland K. , Aigner Achim
Published: June 2011

MicroRNAs (miRNA) aberrantly expressed in tumors may offer novel therapeutic approaches to treatment. miR-145 is downregulated in various cancers including colon carcinoma in which in vitro studies have established proapoptotic and antiproliferative roles. miR-33a was connected recently to cancer through its capacity to downregulate the oncogenic kinase Pim-1. To date, miRNA replacement therapy has been hampered by the lack of robust nonviral delivery methods for in vivo administration. Here we report a method of miRNA delivery by using polyethylenimine (PEI)-mediated delivery of unmodified miRNAs, using miR-145 and miR-33a to preclinically validate the method in a mouse model of colon carcinoma. After systemic or local application of low molecular weight PEI/miRNA complexes, intact miRNA molecules were delivered into mouse xenograft tumors, where they caused profound antitumor effects. miR-145 delivery reduced tumor proliferation and increased apoptosis, with concomitant repression of c-Myc and ERK5 as novel regulatory target of miR-145. Similarly, systemic injection of PEI-complexed miR-33a was validated as a novel therapeutic targeting method for Pim-1, with antitumor effects comparable with PEI/siRNA-mediated direct in vivo knockdown of Pim-1 in the model. Our findings show that chemically unmodified miRNAs complexed with PEI can be used in an efficient and biocompatible strategy of miRNA replacement therapy, as illustrated by efficacious delivery of PEI/miR-145 and PEI/miR-33a complexes in colon carcinoma. Cancer Res; 71(15); 5214–24. ©2011 AACR.
TMPRSS2–ERG-Mediated Feed-Forward Regulation of Wild-Type ERG in Human Prostate Cancers
Authors: Mani Ram-Shankar , Iyer Matthew K. , Cao Qi , Brenner J. Chad , Wang Lei , Ghosh Aparna , Cao Xuhong , Lonigro Robert J. , Tomlins Scott A. , Varambally Sooryanarayana , Chinnaiyan Arul M.
Published: June 2011

Recurrent gene fusions involving ETS family genes are a distinguishing feature of human prostate cancers, with TMPRSS2–ERG fusions representing the most common subtype. The TMPRSS2–ERG fusion transcript and its splice variants are well characterized in prostate cancers; however, not much is known about the levels and regulation of wild-type ERG. By employing an integrative approach, we show that the TMPRSS2–ERG gene fusion product binds to the ERG locus and drives the overexpression of wild-type ERG in prostate cancers. Knockdown of TMPRSS2–ERG in VCaP cells resulted in the downregulation of wild-type ERG transcription, whereas stable overexpression of TMPRSS2–ERG in the gene fusion-negative PC3 cells was associated with the upregulation of wild-type ERG transcript. Further, androgen signaling-mediated upregulation of TMPRSS2–ERG resulted in the concomitant upregulation of wild-type ERG transcription in VCaP cells. The loss of wild-type ERG expression was associated with a decrease in the invasive potential of VCaP cells. Importantly, 38% of clinically localized prostate cancers and 27% of metastatic prostate cancers harboring the TMPRSS2–ERG gene fusions exhibited overexpression of wild-type ERG. Taken together, these results provide novel insights into the regulation of ERG in human prostate cancers. Cancer Res; 71(16); 5387–92. ©2011 AACR.
Hematopoietic Stem Cell Niche Is a Potential Therapeutic Target for Bone Metastatic Tumors
Authors: Shiozawa Yusuke , Pienta Kenneth J. , Taichman Russell S.
Published: June 2011

Despite significant improvements in therapy, the prognosis for cancer with bone metastasis is generally poor. Therefore, there is a great need for new therapeutic approaches for metastatic disease. It has been appreciated that tumor cells metastasize to bone using mechanisms similar to those of hematopoietic stem cells (HSC) homing to bone marrow (e.g., CXCL12/CXCR4). It was recently found that prostate cancer cells target the bone marrow microenvironment for HSCs, or the HSC niche, during metastasis. Of importance, these disseminated prostate cancer cells can be mobilized out of the niche with the use of HSC mobilizing agents. These findings suggest that the bone marrow HSC niche is a potential therapeutic target for metastatic disease. Therefore, a hypothesis worth considering is that agents that can disrupt the interactions between tumor cells and the HSC niche may be efficacious when used in conjunction with standard chemotherapeutic agents. Although further understanding of the tumor-niche interactions is needed, the concept of targeting the niche in conjunction with chemotherapy could open up new possibilities to eradicate incurable metastatic diseases. Clin Cancer Res; 17(17); 5553–8. ©2011 AACR.
Targeting the Mitochondria Activates Two Independent Cell Death Pathways in Ovarian Cancer Stem Cells
Authors: Alvero Ayesha B. , Montagna Michele K. , Holmberg Jennie C. , Craveiro Vinicius , Brown David , Mor Gil
Published: June 2011

Cancer stem cells are responsible for tumor initiation and chemoresistance. In ovarian cancer, the CD44+/MyD88+ ovarian cancer stem cells are also able to repair the tumor and serve as tumor vascular progenitors. Targeting these cells is therefore necessary to improve treatment outcome and patient survival. The previous demonstration that the ovarian cancer stem cells are resistant to apoptotic cell death induced by conventional chemotherapy agents suggests that other forms of targeted therapy should be explored. We show in this study that targeting mitochondrial bioenergetics is a potent stimulus to induce caspase-independent cell death in a panel of ovarian cancer stem cells. Treatment of these cells with the novel isoflavone derivative, NV-128, significantly depressed mitochondrial function exhibited by decrease in ATP, Cox-I, and Cox-IV levels, and by increase in mitochondrial superoxide and hydrogen peroxide. This promotes a state of cellular starvation that activates two independent pathways: (i) AMPKα1 pathway leading to mTOR inhibition; and (ii) mitochondrial MAP/ERK kinase/extracellular signal-regulated kinase pathway leading to loss of mitochondrial membrane potential. The demonstration that a compound can specifically target the mitochondria to induce cell death in this otherwise chemoresistant cell population opens a new venue for treating ovarian cancer patients. Mol Cancer Ther; 10(8); 1385–93. ©2011 AACR.
C-Reactive Protein Predicts the Severity of Coronary Artery Disease Beyond Low-Density Lipoprotein Cholesterol
Authors: Liu Hai-Hang , Zhao Dong , Ma Chang-Sheng , Liu Xiao-Hui , Lv Qiang , Qi Yue , Li Yan , Ren Jie , Liu Jing
Published: June 2011

Prospective studies and clinical trials have shown that C-reactive protein (CRP) independently predicts the occurrence of cardiovascular events, even in individuals without hypercholesterolemia. We evaluated whether CRP can predict the severity of coronary artery stenosis in patients with lower low-density lipoprotein cholesterol (LDL-C) levels. A total of 418 patients with lower LDL-C (<3.37 mmol/L) who underwent coronary angiography were recruited. The median levels of CRP increased according to the number of stenotic vessels. Multivariable adjustment model indicated that CRP was associated with the severity of coronary artery disease (CAD) in the top to the bottom third comparison of CRP levels, yielding an odds ratio of 1.72 (95% confidence interval: 1.08-2.74); this trend was preserved after excluding the confounding effect of statin treatment. C-reactive protein may serve as a useful biomarker for improving the risk assessment and secondary prevention of CAD patients without hypercholesterolemia.
Comparative study of experienced and anticipated stigma in Serbia and the world
Authors: Vidojević Ivona Milačić , Jočić Dragana Ðurić , Tošković Oliver
Published: June 2011

Aim: The presented study is part of the International Study of Discrimination and Stigma Outcomes (INDIGO) conducted in 28 countries. The aim of this study was to compare the degree of experienced and anticipated stigma of patients with schizophrenia in Serbia with world results.

Method: The Discrimination and Stigma Scale (DISC) was applied in individual interviews. The sample comprised 732 subjects of the main study and 50 subjects from Serbia.

Results: The amount of negative experienced discrimination in Serbia is the same as in other participating countries. The Serbian sample shows more negative discrimination in intimate relationships, personal safety and general harm due to the diagnosis, but more positive discrimination within the family, privileges during treatment of somatic illnesses, and benefits enjoyed in social and retirement insurance. The Serbian sample shows less anticipated discrimination in looking for a close relationship and in stopping self from applying for work. The results show that socio-demographic variables could not predict negative experienced and anticipated discrimination, while those same variables enable the prediction of 34% of positive discrimination.

Conclusion: Compared to other investigated countries, stigmatization processes for persons with schizophrenia do not differ considerably in Serbia, which justifies the implementation of unique anti-stigma programmes and joint upgrading of legal regulations.
Structure and properties of flexible polyurethane foams with nano- and micro-fillers
Authors: Javni Ivan , Song Kevin , Lin Jie , Petrovic Zoran S
Published: June 2011

The feasibility of using mineral nano- and micro-fillers as replacement of copolymer polyols in flexible foams was examined. Nano-fillers were nano-clays, a natural montmorillonite (Cloisite Na+) and montmorillonite modified with an organic quaternary ammonium salt (Cloisite 10A), and nano-silica dispersed in methylethylketone. Micro-fillers were micronized clay and silica. Flexible foams were prepared from the ethylene oxide caped polyether triol and toluene diisocyanate with water as the chemical blowing agent. All foams had good morphology except those with nano-clay. The open cell content was above 95%, but air flow was very low in all samples. Micro-fillers did not significantly change cell structure and morphology of hard domains. They moderately increased density, hardness, compression strength, and compression set and decreased elongation at break. The other properties were not affected. Cloisite Na+ (non-treated montmorillonite) and nano-silica with a hydrophilic surface increased hardness, compression strength, and rebound resilience of the foams, whereas Nano-clay 10A (surface-treated montmorillonite) decreased the modulus, hardness, and compression strength. Tensile and tear strengths decreased with the addition of nano-clay fillers, but increased with nano-silica.
Mechanical properties of rigid polyurethane foams at room and cryogenic temperatures
Authors: Stirna U. , Beverte I. , Yakushin V. , Cabulis U.
Published: June 2011

Studies on the effect of the foams’ polymeric matrix’ properties on the tension and compression properties of pour rigid polyurethane (PUR) foams, apparent core density 65—70 kg/m3, at 296 and 77 K were carried out. PUR foams were produced by the hand mixing method from polyol systems that comprised polyether, polyester polyols, and chain extenders. To produce PUR foams, crude MDI was used, and Solkane 365 mfc/227 ea was used as a blowing agent. The molecular weight per branching unit (Mc) of the polymeric matrix of PUR foams was varied in the range 300—1150. Cohesion energy densities of the blocks forming the polymeric matrix were calculated. The effect of Mc on the formation of hydrogen bonds between the urethane groups was estimated from FTIR spectroscopy data and ratio NHbonded /NHfree. It has been found that, with increasing polymeric matrix’ Mc, the tensile strength and elongation at break of PUR foams at 296 and 77 K increases, while Young’s modulus decreases. The increase in the parameter Mc promotes the decrease in the compressive strength and modulus of elasticity of PUR foams at 296 K, while compressive strength indices at 77 K are higher for the foams, whose polymeric matrix has the highest Mc. With increasing polymeric matrix’ M c, the concentration of the urethane groups bonded with hydrogen bonds increases. Structural and mechanical properties of layered spray polyurethane foams, apparent core density approx. 48 kg/m3, having two layers and polymeric matrix’ Mc = 740 were investigated.
Modeling the compressive fracture behavior of foams for energy absorption
Authors: Maurer Myron , Choi Byoung-Ho , Sehanobish Kalyan , Vogel Gavin
Published: June 2011

Polymeric foams and foams in general have a wide variety of applications ranging from energy absorption, noise and vibration absorption, and thermal insulation. In some segments of transportation applications, foams are used specifically for energy absorption during a vehicle crash. These foams are designed for one-time use to protect vehicle occupants where recoverability of the foam is not prescribed. Recently, it has been identified that a ‘square-wave’ load versus displacement response is desired for these applications. Observations of foam crushing during compression have demonstrated the need for an appropriate phenomenological model for foam failure. Current foam—structure—property models do not go all the way to final failure and can predict the early stage of load—displacement relationship. But, in terms of energy absorption, the model which covers the extensive load—displacement relationship is very important. This article will detail the development of a structure—property model used throughout the development of a new family of lightweight, space efficient, energy absorbing foams.
Autoclave preparation of expanded polypropylene/poly(lactic acid) blend bead foams with a batch foaming process
Authors: Tang Linqi , Zhai Wentao , Zheng Wenge
Published: June 2011

Due to the well-defined mechanical properties and high service temperature, considerable efforts have been devoted to the development of expanded polypropylene bead foams nowadays. A pilot scale batch foaming equipment with volume of 50 L was carried out to produce polypropylene and polypropylene/poly(lactic acid) bead foams with using n-pentane as the physical blowing agent. The resultant bead foams exhibited high expansion ratio up to 44.4, nice ellipse bead foam shape, well-defined cell structure and quite high cell density. Neat PP exhibited a narrow foaming temperature window around 4—5°C. Poly(lactic acid) possessed high n-pentane solubility, and the presence of 20% poly(lactic acid) was verified to obviously broaden the foaming temperature window to 10—15°C and facilitated the foam expansion. In this study, the fundamental issues such as pressure building in autoclave, n-pentane solubility, and various parameters to control bead foams’ expansion and cell morphology are presented.
Factors Associated With Where Secondary Students With Disabilities Are Educated and How They Are Doing
Authors: Wilson Gloria Lodato , Kim Sun A , Michaels Craig A.
Published: June 2011

The focus of this study was on increasing the knowledge base on students with disabilities at the secondary level. Data were gathered on 559 classified secondary students with disabilities served in four educational options: cotaught classes, resource rooms, alternate day support programs, and no direct supports. Results indicate that there are associations between classification and placement options, differences in full-scale IQ by placement option, differences in the numbers of related services and the number of testing accommodations students receive based on placement option, associations among placement option and both related services and testing accommodations, and no differences in grades by placement option. Implications for future research and practice are discussed.
A model for numerical simulation of heat and water vapor exchange in multilayer textile packages with three-dimensional spacer fabric ventilation layer
Authors: Barauskas Rimantas , Abraitiene Ausra
Published: June 2011

The work presents a structural computational model developed for investigation of heat and air—water vapor mass exchange between the multilayer textile packages and the human body. Each fabric layer is represented by a single element, characterized by its air and water vapor permeability, thermal resistance and heat capacity, as well as, water vapor absorption properties. While characteristics of each layer are obtained experimentally, the computational model enables the prediction of the variation in time of temperature and humidity in the gaps between each pair of adjacent layers. The finite element, which represents the forced ventilation layer made of three-dimensional textile material, is created and may be used as a structural element within the overall structural model of the textile package. The element equations are derived on the basis of ideal gas state equation. The results of the measured textile layers characteristics and the numerical data are presented. Though the condensation of water vapor was not considered in this model, the time point of initiation of sweating at given heat and water vapor generation rates could be predicted.
An improved model of rigid bodies for plain-weave fabrics based on the dynamics of multibody systems
Authors: Mingxing Xiao  , Zhaofeng Geng  , Kaijun Liao
Published: June 2011

This paper proposes an improved model of rigid bodies for plain-weave fabrics (IMRBF) by applying the dynamics of multibody systems theory. Firstly, considering that in the model of rigid bodies for plain-weave fabrics (MRBF), the rigid bodies of the fabric system are straight linear threads, in this paper, simplified Cardan angular coordinates composed of only two independent variables are adopted to describe the rotation of each body. Hence, the dimension of the equations of motion of the system is reduced, and the computational efficiency is improved greatly. Secondly, the point—point contact model is applied to simulate the contact action between yarns when the corresponding unit cell is under shearing deformation. This approach makes the IMRBF closer to the mechanical performance of actual fabrics and more broadly applicable. The model is validated by comparing our simulation results with those obtained from the Kawabata Evaluation System for Fabrics uniaxial tensile experiments and shearing experiments. Furthermore, by comparing the simulation results of the MRBF and the IMRBF, the improved computational efficiency and broader applicability of the IMRBF are demonstrated.
Morphology and mechanical properties of antibacterial nylon 6/nano-silver nano-composite multifilament yarns
Authors: Damerchely Rogheih , Mohammad Esmail Yazdanshenas  , Rashidi Abo-Saeed , Khajavi Ramin
Published: June 2011

In this research, some physical, mechanical and antibacterial properties of melt-spun nylon 6/nano-silver multifilament yarns have been studied. Characteristics of nano-composite multifilament yarns were studied by tensile testing, scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry and energy dispersive X-ray. The antibacterial efficiency of produced yarns was estimated by quantitative AATCC-100 test method. According to the results, it was concluded that, sample yarns with 0.5—1 wt% content of nano-silver possessed acceptable antibacterial activity and their mechanical properties did not change significantly.