bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution analysis of the main mechanisms of the jet/vortex interaction
Authors: Depommier Guillaume , Labbé Odile , Sagaut Pierre 
Published: August 2010

AbstractA new analysis method of the jet/vortex interaction is presented to better understand the effect of each vortical structure on the others composing the jet and even on itself. Vortical structures are isolated from each other and the velocity field they produce is calculated by means of the Biot–Savart law. The structure influence on each another is then distinguished from the others by using its velocity field in the calculation of the vorticity momentum equations. Based on 3D‐datafields provided by a large‐eddy‐simulation (LES) of the interaction between a Lamb–Oseen vortex and a turbulent round jet, a post‐processing tool educes the vortical structures and quantifies the different vorticity momentum equations terms. The study has been limited to the first steps of the interaction regime when there are still few vortical structures so that the subsequent analysis of the post‐process results remains simple enough to be performed. The present method confirmed the intensification of azimuthal structures as they roll up around the main vortex. Core disturbance of the latter was found to be initially caused by those structures and not by core dynamic instabilities, which become dominant with the appearance of non‐linear mechanisms. Copyright © 2010 John Wiley & Sons, Ltd.
A new well‐balanced Hermite weighted essentially non‐oscillatory scheme for shallow water equations
Authors: Caleffi Valerio 
Published: August 2010

AbstractHermite weighted essentially non‐oscillatory (HWENO) methods were introduced in the literature, in the context of Euler equations for gas dynamics, to obtain high‐order accuracy schemes characterized by high compactness (e.g. Qiu and Shu, J. Comput. Phys. 2003; 193:115). For example, classical fifth‐order weighted essentially non‐oscillatory (WENO) reconstructions are based on a five‐cell stencil whereas the corresponding HWENO reconstructions are based on a narrower three‐cell stencil. The compactness of the schemes allows easier treatment of the boundary conditions and of the internal interfaces. To obtain this compactness in HWENO schemes both the conservative variables and their first derivatives are evolved in time, whereas in the original WENO schemes only the conservative variables are evolved.In this work, an HWENO method is applied for the first time to the shallow water equations (SWEs), including the source term due to the bottom slope, to obtain a fourth‐order accurate well‐balanced compact scheme. Time integration is performed by a strong stability preserving the Runge–Kutta method, which is a five‐step and fourth‐order accurate method. Besides the classical SWE, the non‐homogeneous equations describing the time and space evolution of the conservative variable derivatives are considered here. An original, well‐balanced treatment of the source term involved in such equations is developed and tested. Several standard one‐dimensional test cases are used to verify the high‐order accuracy, the C‐property and the good resolution properties of the model. Copyright © 2010 John Wiley & Sons, Ltd.
Identification of novel carcinogen‐mediated mammary tumor susceptibility loci in the rat using the chromosome substitution technique
Authors: Adamovic Tatjana , McAllister Donna , Wang Tao , Adamovic Dragan , Rowe J. Jordi , Moreno Carol , Lazar Josef , Jacob Howard J. , Sugg Sonia L. 
Published: August 2010

AbstractWe here report the genetic basis for susceptibility and resistance to carcinogen‐mediated [7,12‐dimethylbenz[a]anthracene (DMBA)] mammary tumorigenesis using the full panel of SS/BN consomic rat strains, in which substitutions of individual chromosomes from the resistant BN strain onto the genomic background of the susceptible SS strain were made. Analysis of 252 consomic females identified rat mammary Quantitative Trait Loci (QTLs) affecting tumor incidence on chromosomes 3 and 5, latency on chromosomes 3, 9, 14, and 19, and multiplicity on chromosomes 13, 16, and 19. In addition, we unexpectedly identified a novel QTL on chromosome 6 controlling a lethal toxic phenotype in response to DMBA. Upon further investigation with chromosomes 6 and 13 congenic lines, in which an additional 114 rats were investigated, we mapped (1) a novel mammary tumor QTL to a region of 27.1 Mbp in the distal part of RNO6, a region that is entirely separated from the toxicity phenotype, and (2) a novel and powerful mammary tumor susceptibility locus of 4.5 Mbp that mapped to the proximal q‐arm of RNO13. Comparison of genetic strain differences using existing rat genome databases enabled us to further construct priority lists containing single breast cancer candidate genes within the defined QTLs, serving as potential functional variants for future testing. © 2010 Wiley‐Liss, Inc.
CKS1B amplification is a frequent event in cutaneous squamous cell carcinoma with aggressive clinical behaviour
Authors: Salgado Rocío , Toll Agustí , Alameda Francesc , Baró Teresa , Martín‐Ezquerra Gemma , Sanmartín Onofre , Martorell‐Calatayud Antonio , Salido Marta , Almenar Sergio , Solé Francesc , Pujol Ramon M. , Espinet Blanca 
Published: August 2010

AbstractGenetic mechanisms giving rise to the development of cutaneous squamous cell carcinoma (cSCC) are poorly understood and development of genomic high resolution techniques has led to a better knowledge of the genetic basis of several human cancers. In this study, 16 cSCC were analyzed using array comparative genomic hybridization (arrayCGH). The most common aberrations found were gains of 3q11q13, 1q21.3q25, 13q34, and 19p13, and losses of 1p36p31, 3p24p21, 10p15q22, and 13q11q21. We detected gains (3/16) and amplification (1/16) of the 1q21.1q21.3 region. A potential candidate gene in this region, CKS1B (1q21.2), was selected for validation in an independent cohort and correlations with clinicopathological features were carried out. CKS1B gene and protein status were analyzed using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in a series of 53 cSCC, 22 actinic keratoses (AK), and 10 normal skin samples. cSCC presented a higher frequency of chromosome 1 polysomy than AK (70% vs. 46%, P = 0.047). Association between CKS1B protein overexpression and both polysomy and amplification was demonstrated in cSCC (P < 0.001). Regarding amplifications, 11 cSCC patients (21%) presented CKS1B gene amplification. Interestingly, 8/11 (73%) patients who showed a CKS1B amplification had presented metastatic spread (mcSCC). Differences between the presence of CKS1B amplification and the presence or absence of mcSCC were observed (mcSCC [8/14] vs. cSCC [3/39]) (P < 0.001). Several drugs targeting CKS1B have been reported and may be useful for treating patients with cSCC and CKS1B amplifications. © 2010 Wiley‐Liss, Inc.
Small deletions but not methylation underlie CDKN2A/p16 loss of expression in conventional osteosarcoma
Authors: Mohseny Alexander B. , Tieken Chris , van der Velden Pieter A. , Szuhai Karoly , de Andrea Carlos , Hogendoorn Pancras C. W. , Cleton‐Jansen Anne‐Marie 
Published: August 2010

AbstractConventional osteosarcoma is characterized by rapid growth, high local aggressiveness, and metastasizing potential. Patients developing lung metastases experience poor prognosis despite extensive chemotherapy regimens and surgical interventions. Previously we identified a subgroup of osteosarcoma patients with loss of CDKN2A/p16 protein expression in the primary tumor biopsies which was significantly predictive of a very poor prognosis. Here we aimed to identify the underlying mechanism(s) of this protein loss in relation to osteosarcoma behavior. The CDKN2A locus was analyzed in osteosarcoma cases with total loss of CDKN2A/p16 expression and in cases with high protein expression using melting curve analysis‐methylation assay (MCA‐Meth), fluorescent in situ hybridization (FISH), multiplex ligation‐dependent probe amplification (MLPA), and mutation analysis. All cases with complete CDKN2A/p16 protein loss showed homozygous deletions at the CDKN2A locus. In none of the cases hyper methylation of the promoter region was seen which was confirmed by sequencing this region. Taken together we show that large or smaller deletions of the CDKN2A locus are evident in patient samples and underlie the CDKN2A/p16 protein expression loss while promoter methylation does not appear to be a mechanism of this expression loss. Genomic loss of CDKN2A instead of promoter methylation might be a plausible explanation for the rapid proliferation and high aggressiveness of osteosarcoma by simultaneous impairment CDKN2A/p14ARF function. © 2010 Wiley‐Liss, Inc.
Tubulin polymerization promoting protein (TPPP/p25) as a marker for oligodendroglial changes in multiple sclerosis
Authors: Höftberger Romana , Fink Stephanie , Aboul‐Enein Fahmy , Botond Gergö , Olah Judit , Berki Timea , Ovadi Judit , Lassmann Hans , Budka Herbert , Kovacs Gabor G. 
Published: August 2010

AbstractMultiple sclerosis (MS) is an idiopathic chronic inflammatory demyelinating disease of the central nervous system with variable extent of remyelination. Remyelination originates from oligodendrocyte (OG) precursor cells, which migrate and differentiate into mature OG. Tubulin polymerization promoting protein (TPPP/p25) is located in mature OG and aggregates in oligodendroglial cytoplasmic inclusions in multiple system atrophy. We developed a novel monoclonal anti‐TPPP/p25 antibody to quantify OG in different subtypes and disease stages of MS, and possible degenerative changes in OG. We evaluated autopsy material from 25 MS cases, including acute, primary progressive, secondary progressive, relapsing remitting MS, and five controls. Demyelinated lesions revealed loss of TPPP/p25‐positive OG within the plaques. In remyelination, TPPP/p25 was first expressed in OG cytoplasms and later became positive in myelin sheaths. We observed increased numbers of TPPP/p25 immunoreactive OG in the normal appearing white matter (NAWM) in MS patients. In MS cases, the cytoplasmic area of TPPP/p25 immunoreactivity in the OG was higher in the periplaque area when compared with NAWM and the plaque, and TPPP/p25 immunoreactive OG cytoplasmic area inversely correlated with the disease duration. There was a lack of phospho‐TDP‐43, phospho‐tau, α‐synuclein, and ubiquitin immunoreactivity in OG with enlarged cytoplasm. Our data suggest impaired differentiation, migration, and activation capacity of OG in later disease stages of MS. Upregulation of TPPP/p25 in the periplaque white matter OG without evidence for inclusion body formation might reflect an activation state. Distinct and increased expression of TPPP/p25 in MS renders it a potential prognostic and diagnostic marker of MS. © 2010 Wiley‐Liss, Inc.
Astrocyte‐derived glutathione attenuates hemin‐induced apoptosis in cerebral microvascular cells
Authors: Sukumari‐Ramesh Sangeetha , Laird Melissa D. , Singh Nagendra , Vender John R. , Alleyne Cargill H. , Dhandapani Krishnan M. 
Published: August 2010

AbstractIntracerebral hemorrhage (ICH) induces neurovascular injury via poorly defined mechanisms. The aim of this study was to determine whether gliovascular communication may restrict hemorrhagic vascular injury. Hemin, a hemoglobin by‐product, concentration‐ and time‐dependently increased apoptotic cell death in mouse bEnd.3 cells and in primary human brain microvascular endothelial cells, at least in part, via a caspase‐3 dependent pathway. Cell death was preceded by a NFκB‐mediated increase in inflammatory gene expression, including upregulation of inducible nitric oxide synthase (iNOS) expression and activity. Functionally, inhibition of iNOS or the addition of a peroxynitrite decomposition catalyst reduced cell death. Interestingly, co‐treatment with astrocyte‐conditioned media (ACM) reversed hemin‐induced NFκB activation, nitrotyrosine formation, and apoptotic cell death, at least in part, via the release of the endogenous antioxidant, reduced glutathione (GSH). Prior treatment of astrocytes with the GSH‐depleting agent, DL‐buthionine (S,R)‐sulfoximine or direct addition of diethyl maleate, a thiol‐depleting agent, to ACM reversed the observed protection. In contrast, neither exogenous GSH nor the GSH precursor, N‐acetylcysteine, was protective in bEnd.3 cells. Together, these data support an important role for astrocyte‐derived GSH in the maintenance of oxidative balance in the vasculature and suggest therapeutic targeting of the GSH system may reduce neurological injury following ICH. © 2010 Wiley‐Liss, Inc.
Spinal injection of TNF‐α‐activated astrocytes produces persistent pain symptom mechanical allodynia by releasing monocyte chemoattractant protein‐1
Authors: Gao Yong‐Jing , Zhang Ling , Ji Ru‐Rong 
Published: August 2010

AbstractAccumulating evidence suggests that spinal astrocytes play an important role in the genesis of persistent pain, by increasing the activity of spinal cord nociceptive neurons, i.e., central sensitization. However, direct evidence of whether activation of astrocytes is sufficient to induce chronic pain symptoms is lacking. We investigated whether and how spinal injection of activated astrocytes could produce mechanical allodynia, a cardinal feature of chronic pain, in naïve mice. Spinal (intrathecal) injection of astrocytes, which were prepared from cerebral cortexes of neonatal mice and briefly stimulated by tumor necrosis factor‐alpha (TNF‐α), induced a substantial decrease in paw withdrawal thresholds, indicating the development of mechanical allodynia. This allodynia was prevented when the astrocyte cultures were pretreated with a peptide inhibitor of c‐Jun N‐terminal kinase (JNK), D‐JNKI‐1. Of note a short exposure of astrocytes to TNF‐α for 15 min dramatically increased the expression and release of the chemokine monocyte chemoattractant protein‐1 (MCP‐1), even 3 h after TNF‐α withdrawal, in a JNK‐dependent manner. In parallel, intrathecal administration of TNF‐α induced MCP‐1 expression in spinal cord astrocytes. In particular, mechanical allodynia induced by TNF‐α‐activated astrocytes was reversed by a MCP‐1 neutralizing antibody. Finally, pretreatment of astrocytes with MCP‐1 siRNA attenuated astrocytes‐induced mechanical allodynia. Taken together, our results suggest that activated astrocytes are sufficient to produce persistent pain symptom in naïve mice by releasing MCP‐1. © 2010 Wiley‐Liss, Inc.
Physiologic role for “inducible” nitric oxide synthase: A new form of astrocytic–neuronal interface
Authors: Amitai Yael 
Published: August 2010

AbstractNitric oxide (NO) has been long recognized as an atypical neuronal messenger affecting excitatory synaptic transmission, but its cellular source has remained unresolved as the neuronal isoform of NO synthase (nNOS) in many brain regions is expressed only by small subsets of inhibitory neurons. It is generally believed that the glial NO‐producing isoform (iNOS) is not expressed in the normal brain, but rather it undergoes a transcription‐mediated up‐regulation following an immunological challenge. Therefore, the involvement of iNOS in modulating normal neuronal functions has been largely ignored. Here I review evidence to the contrary: I summarize data pointing to the existence of a functioning iNOS in normal undisturbed mammalian brains, and experimental results tracing this expression to astrocytes. Finally, I review recent findings asserting that iNOS‐dependent NO modulates synaptic release from presynaptic terminals. Based on these data, I propose that astrocytes express basal levels of iNOS. Flanking synaptic elements, astrocytes are perfectly positioned to release NO and affect synaptic transmission. © 2010 Wiley‐Liss, Inc.
Glucosamine exerts a neuroprotective effect via suppression of inflammation in rat brain ischemia/reperfusion injury
Authors: Hwang So‐Young , Shin Joo‐Hyun , Hwang Ji‐Sun , Kim Song‐Yi , Shin Jin‐A , Oh Eok‐Soo , Oh Seikwan , Kim Jung‐Bin , Lee Ja‐Kyung , Han Inn‐Oc 
Published: August 2010

AbstractWe investigated the neuroprotective effect of glucosamine (GlcN) in a rat middle cerebral artery occlusion model. At the highest dose used, intraperitoneal GlcN reduced infarct volume to 14.3% ± 7.4% that of untreated controls and afforded a reduction in motor impairment and neurological deficits. Neuroprotective effects were not reproduced by other amine sugars or acetylated‐GlcN, and GlcN suppressed postischemic microglial activation. Moreover, GlcN suppressed lipopolysaccharide (LPS)‐induced upregulation of proinflammatory mediators both in vivo and in culture systems using microglial or macrophage cells. The anti‐inflammatory effects of GlcN were mainly attributable to its ability to inhibit nuclear factor kappaB (NF‐κB) activation. GlcN inhibited LPS‐induced nuclear translocation and DNA binding of p65 to both NF‐κB consensus sequence and NF‐κB binding sequence of inducible nitric oxide synthase promoter. In addition, we found that GlcN strongly repressed p65 transactivation in BV2 cells using Gal4‐p65 chimeras system. P65 displayed increased O‐GlcNAcylation in response to LPS; this effect was also reversed by GlcN. The LPS‐induced increase in p65 O‐GlcNAcylation was paralleled by an increase in interaction with O‐GlcNAc transferase, which was reversed by GlcN. Finally, our results suggest that GlcN or its derivatives may serve as novel neuroprotective or anti‐inflammatory agents. © 2010 Wiley‐Liss, Inc.
Astrocytes contacting HIV‐1‐infected macrophages increase the release of CCL2 in response to the HIV‐1‐dependent enhancement of membrane‐associated TNFα in macrophages
Authors: Muratori Claudia , Mangino Giorgio , Affabris Elisabetta , Federico Maurizio 
Published: August 2010

AbstractThe presence of human immunodeficiency virus (HIV)‐infected macrophages in the parenchyma of central nervous system is an hallmark of acquired immunodeficiency syndrome‐related neuroinflammation. Once penetrated the blood–brain barrier (BBB), macrophages closely interact with astrocytes, beginning with those lying beneath the BBB endothelium. By investigating the consequences of the cell–cell interaction between HIV‐infected macrophages and astrocytes, we observed that the HIV‐1 expression in macrophagic cells correlated with increased chemotactic activity in supernatants of astroglial cells. Gene array analysis revealed an impressive increase in the transcription of the gene for the CCL2/MCP‐1 chemokine in astroglial cells isolated from HIV‐1‐infected co‐cultures compared with cells from uninfected co‐cultures. This phenomenon coupled with the increase in CCL2 release and depended on the cell–cell contact. In addition, it was a consequence of the HIV‐1‐induced enhancement of membrane‐associated tumor necrosis factor‐α in macrophagic cells, and correlated with increased levels of nuclear factor kappaB activation in astroglial cells. These observations could mirror a mechanism of recruitment of leukocytes through the BBB, likely contributing to the increase in both viral load and inflammation in central nervous system of HIV‐infected patients. © 2010 Wiley‐Liss, Inc.
Manganese‐induced downregulation of astroglial glutamine transporter SNAT3 involves ubiquitin‐mediated proteolytic system
Authors: Sidoryk‐Wȩgrzynowicz Marta , Lee Eun‐Sook , Ni Mingwei , Aschner Michael 
Published: August 2010

AbstractSNAT3 is a major facilitator of glutamine (Gln) efflux from astrocytes, supplying Gln to neurons for neurotransmitter synthesis. Our previous investigations have shown that, in primary cortical astrocyte cultures, SNAT3 protein is degraded after exposure to manganese (Mn2+). The present studies were performed to identify the processes responsible for this effect. One of the well‐established mechanisms for protein‐level regulation is posttranslational modification via ubiquitination, which leads to the rapid degradation of proteins by the 26S proteasome pathway. Here, we show that astrocytic SNAT3 directly interacts with the ubiquitin ligase, Nedd4‐2 (neural precursor cells expressed developmentally downregulated 4‐2), and that Mn2+ increases both Nedd4‐2 mRNA and protein levels. Additionally, we have found that Mn2+ exposure elevates astrocytic ubiquitin B mRNA expression, free ubiquitin protein levels, and total protein ubiquitination. Furthermore, Mn2+ effectively decreases astrocytic mRNA expression and the phosphorylation of serum and glucocorticoid‐inducible kinase, a regulatory protein, which, in the active phosphorylated form, is responsible for the phosphorylation and subsequent inactivation of Nedd4‐2. Additional findings establish that Mn2+ increases astrocytic caspase‐like proteolytic proteasome activity and that the Mn2+‐dependent degradation of SNAT3 protein is blocked by the proteasome inhibitors, N‐acetyl‐leu‐leu‐norleucinal and lactacystin. Combined, these results demonstrate that Mn2+‐induced SNAT3 protein degradation and the dysregulation of Gln homeostasis in primary astrocyte cultures proceeds through the ubiquitin‐mediated proteolytic system. © 2010 Wiley‐Liss, Inc.
Pyridoxal‐5′‐phosphate phosphatase/chronophin induces astroglial apoptosis via actin‐depolymerizing factor/cofilin system in the rat brain following status epilepticus
Authors: Kim Ji‐Eun , Ryu Hea Jin , Kim Min‐Ju , Kim Dae‐Won , Kwon Oh‐Shin , Choi Soo Young , Kang Tae‐Cheon 
Published: August 2010

AbstractActin‐depolymerizing factor (ADF)/cofilin is a small cytoskeletal protein that is a stimulus‐responsive mediator of actin dynamics. ADF/cofilin also translocates into mitochondria and nuclei in response to apoptotic stimuli for cytochrome c release. These ADF/cofilin translocations are negatively regulated by phosphorylation. Recently, it has been reported that pyridoxal‐5′‐phosphate (PLP) phosphatase/chronophin (PLPP/CIN) regulates phosphorylation of ADF/cofilin levels. Therefore, we investigated whether PLPP/CIN contributes to apoptosis‐like events via modulation of ADF/cofilin phosphorylation following status epilepticus (SE). In the present study, apoptosis‐like astroglial damages were detected in the dentate gyrus after SE. Upregulation of ADF/cofilin and PLPP/CIN expression in the cytoplasm and nucleus were accompanied by apoptosis‐like events. PLPP/CIN level showed a direct proportionality to nuclear translocation of ADF/cofilin. Moreover, nuclear accumulation of apoptosis‐inducing factor was simultaneously observed with that of ADF/cofilin. Tat‐PLPP/CIN pretreatment accelerated astroglial apoptosis‐like degeneration following SE, although Tat‐PLPP/CIN transduction alone could not induce apoptosis or necrosis in astrocytes. Therefore, our findings suggest that nuclear accumulation of ADF/cofilin itself may not induce apoptogenic events, but may play a synergic role in apoptosis‐like astroglial loss following SE. © 2010 Wiley‐Liss, Inc.