bluuebunny/crossref_metadata_2025 huggingface dataset:
A distinct subset of glioma cell lines with stem cell‐like properties reflects the transcriptional phenotype of glioblastomas and overexpresses CXCR4 as therapeutic target
Authors: Schulte Alexander , Günther Hauke S. , Phillips Heidi S. , Kemming Dirk , Martens Tobias , Kharbanda Samir , Soriano Robert H. , Modrusan Zora , Zapf Svenja , Westphal Manfred , Lamszus Katrin
Published: February 2011

Glioblastomas contain stem‐like cells that can be maintained in vitro using specific serum‐free conditions. We investigated whether glioblastoma stem‐like (GS) cell lines preserve the expression phenotype of human glioblastomas more closely than conventional glioma cell lines. Expression profiling revealed that a distinct subset of GS lines, which displayed a full stem‐like phenotype (GSf), mirrored the expression signature of glioblastomas more closely than either other GS lines or cell lines grown in serum. GSf lines are highly tumorigenic and invasive in vivo, express CD133, grow spherically in vitro, are multipotent and display a Proneural gene expression signature, thus recapitulating key functional and transcriptional aspects of human glioblastomas. In contrast, GS lines with a restricted stem‐like phenotype exhibited expression signatures more similar to conventional cell lines than to original patient tumors, suggesting that the transcriptional resemblance between GS lines and tumors is associated with different degrees of “stemness”. Among markers overexpressed in patient tumors and GSf lines, we identified CXCR4 as a potential therapeutic target. GSf lines contained a minor population of CXCR4hi cells, a subfraction of which coexpressed CD133 and was expandable by hypoxia, whereas conventional cell lines contained only CXCR4lo cells. Convection‐enhanced local treatment with AMD3100, a specific CXCR4 antagonist, inhibited the highly invasive growth of GS xenografts in vivo and cell migration in vitro. We thus demonstrate the utility of GSf lines in testing therapeutic agents and validate CXCR4 as a target to block the growth of invasive tumor‐initiating glioma stem cells in vivo. © 2011 Wiley‐Liss, Inc.
Inducible gene expression in GFAP+ progenitor cells of the SGZ and the dorsal wall of the SVZ—A novel tool to manipulate and trace adult neurogenesis
Authors: Weber Tillmann , Baier Vera , Pauly Rahel , Sahay Amar , Baur Max , Herrmann Elke , Ciccolini Francesca , Hen René , Kronenberg Golo , Bartsch Dusan
Published: February 2011

In the adult mammalian brain, neurogenesis originates from astrocyte‐like stem cells. We generated a transgenic mouse line in which the tetracycline dependent transactivator (tTA) is expressed under the control of the murine GFAP promoter. In this mouse line, inducible gene expression targets virtually all GFAP‐expressing stem‐like cells in the dentate gyrus and a subset of GFAP‐expressing progenitors located primarily in the dorsal wall/dorsolateral corner of the subventricular zone. Outside the neurogenic zones, astrocytes are infrequently targeted. We introduce a panel of transgenic mice which allow both inducible expression of candidate genes under control of the murine GFAP promoter and, at the same time, lineage tracing of all cells descendant from the original GFAP‐positive cell. This new mouse line represents a versatile tool for functional analysis of neurogenesis and lineage tracing. © 2011 Wiley‐Liss, Inc.
Isocitrate dehydrogenase mutations: A challenge to traditional views on the genesis and malignant progression of gliomas
Authors: Weller Michael , Wick Wolfgang , von Deimling Andreas
Published: February 2011

Isocitrate dehydrogenases (IDHs) convert isocitrate to α‐ketoglutarate by oxidative decarboxylation and are thereby involved in multiple metabolic processes. Mutations in the genes encoding IDH1 and IDH2 were first reported in human gliomas in 2008 and later on also identified in a minority of patients with acute myeloid leukemia. The mutations universally affect codons 132 in IDH1 and 172 in IDH2 and result in decreased enzymatic activity. The oncogenic pathway triggered by IDH mutations may involve the activation of hypoxia‐inducible factor pathway as well as the acquisition of a novel (gain of enzymatic) function consuming NADPH and generating α‐hydroxyglutarate. Most intriguingly, IDH mutations are observed in ∼70–80% of grade II/III gliomas and the majority of secondary glioblastomas, but only 10% of primary glioblastomas, suggesting a different cellular origin of the gliomas, which had previously been viewed as a multistep process of malignant progression. Understanding the oncogenic pathway mediated by mutant IDH might result in the development of novel, tailored pharmacological therapies for human glioma patients. © 2011 Wiley‐Liss, Inc.
An Alzheimer's disease‐relevant presenilin‐1 mutation augments amyloid‐beta‐induced oligodendrocyte dysfunction
Authors: Desai Maya K. , Guercio Brendan J. , Narrow Wade C. , Bowers William J.
Published: February 2011

White matter pathology has been documented in the brains of familial Alzheimer's disease (FAD)‐afflicted individuals during presymptomatic and preclinical stages of AD. How these defects in myelination integrity arise and what roles they may play in AD pathophysiology have yet to be fully elucidated. We previously demonstrated that triple‐transgenic AD (3xTg‐AD) mice, which harbor the human amyloid precursor Swedish mutation, presenilin‐1 M146V (PS1M146V) knock‐in mutation, and tauP301Lmutation, exhibit myelin abnormalities analogous to FAD patients and that Aβ1‐42contributes to these white matter deficits. Herein, we demonstrate that the PS1M146Vmutation predisposes mouse oligodendrocyte precursor (mOP) cells to Aβ1‐42‐induced alterations in cell differentiationin vitro. Furthermore, PS1M146Vexpression compromised mOP cell function and MBP protein distribution, a process that is further aggravated with exposure to Aβ1‐42. We found that the myelination defect and MBP subcellular mislocalization triggered by PS1M146Vand Aβ1‐42can be effectively prevented by treatment with the GSK‐3β inhibitor, TWS119, thereby implicating GSK‐3β kinase activity in this pathogenic cascade. Overall, this work provides further mechanistic insights into PS1M146Vand Aβ1‐42‐driven oligodendrocyte dysfunction andmyelin damage during early presymptomatic stages of AD, and provides a new target in oligodendrocytes for developing therapies designed to avert AD‐related white matter pathology. © 2011 Wiley‐Liss, Inc.
FOXO3a inhibits TNF‐α‐ and IL‐1β‐induced astrocyte proliferation:Implication for reactive astrogliosis
Authors: Cui Min , Huang Yunlong , Tian Changhai , Zhao Yong , Zheng Jialin
Published: February 2011

Reactive astrogliosis is one of the pathological hallmarks of neurodegenerative diseases. Inflammatory cytokines, such as TNF‐α and IL‐1β, have been shown to mediate the reactive astrogliosis in neurodegenerative diseases; however, the molecular mechanism remains unclear. In this study, we investigated the role of transcription factor FOXO3a on astrocyte proliferation, one primary aspect of severe reactive astrogliosis. Our results confirmed that TNF‐α and IL‐1β increased astrocyte proliferation, as determined by Ki67 and BrdU immunostaining. Furthermore, we found that cytokine‐mediated astrocyte proliferation was accompanied by an increase of the phosphorylation and reduced nuclear expression of FOXO3a. Intracranial injection of TNF‐α and IL‐1β induced astrocyte proliferation and hypertrophy, which was associated with reduced nuclear expression of Foxo3a in astrocytes. To determine the function of FOXO3a in astrocyte proliferation, wild type FOXO3a was overexpressed with adenovirus, which subsequently upregulated p27Kip1 and Gadd45α, and significantly inhibited cytokine‐induced astrocyte proliferation. In contrast, overexpression of dominant negative FOXO3a decreased p27Kip1, upregulated cyclin D1 and promoted astrocyte proliferation. Along the same line, astrocytes isolated from Foxo3a‐null mice have higher proliferative potential. In response to intracranial injection of cytokines, Foxo3a‐null mice manifested severe astrogliosis in vivo. In conclusion, FOXO3a is important in restraining astrocyte proliferation during proinflammatory cytokine stimulation and loss of function of FOXO3a may be responsible for the proliferation of astrocytes in the severe form of reactive astrogliosis. Understanding the key regulatory role of FOXO3a in reactive astrogliosis may provide a novel therapeutic target during neuroinflammation. © 2011 Wiley‐Liss, Inc.
Zusammensetzung der Neutrallipide und deren Fettsäuren aus Wal‐Hirnen. II. Hirne von Finnwalen (Balaenoptera physalus)
Authors: Lesch Peter , Bernhard Karl
Published: February 2011

Pure lipids from 5 regions of brains from 6 whales have been separated into various fractions as cerebrosides, sphingomyelines, lecithines, ethanolamine cephalines, cholesterol and free fatty acids. The white matter contains mostly cholesterol and cerebrosides, the grey matter glycerophosphatides. The fatty acid composition of the cerebrosides from all regions is about the same. The fatty acids from sphingomyelines, lecithines, ethanolamine cephalines show significant differences in relation to their origin.
Etude de cyclohexanediols par spectrométrie de masse
Authors: Buchs A.
Published: February 2011

Low resolution mass spectra of cyclohexane‐1,2‐diols and of deuterium labelled cyclohexane‐1,2‐diols cis and trans have been measured. The results indicate that it is easy to differentiate between positional isomers and that the stereochemistry of cyclohexane‐1,2‐diols can be deduced from the mass spectra. In the 1,2‐diols the elimination of water under electron impact occurs simultaneously in three ways: (a) between an OH group and a H atom in position 1,4, (b) between the two OH groups, (c) without participation of the II atoms of the OH groups. Difficulties encountered in deducing unambiguous fragmentation patterns are discussed.
ESR.‐Messungen an Radikal‐Anionen Trimethylsilyl‐substituierter π‐Elektronensysteme
Authors: Gerson F. , Heinzer J. , Bock H. , Alt H. , Seidl H.
Published: February 2011

The ESR spectra of the radical anions of several trimethylsilyl substituted polyenes, benzenes and naphthalenes have been recorded; most of them are surprisingly stable under the conditions of measurement. Accurate values could be obtained for the splitting parameters – not only of the protons, but also of the 29Si isotopes in natural abundance. The coupling constants of the 29Si nuclei in trimethylsilyl substituents are of the same order of magnitude as the corresponding values of the protons attached to centers of comparable π‐spin population. The results indicate some Si ← Cπ delocalization.
Die Dienol‐Benzol‐Umlagerung von Allyldienolen: aromatische [1,2]‐, [3,3]‐ und [3,4]‐sigmatropische Umlagerungen
Authors: Hansen H.‐J. , Sutter B. , Schmid H.
Published: February 2011

The dienol‐benzene rearrangement of syn and anti‐4‐allyl‐4‐methylcyclohexa‐2,5‐dien‐1‐ol (syn and anti 15) occurs by formation of a benzonium ion intermediate in p‐toluene‐sulphonic acid in ether below 0° and leads to a mixture of 2‐, 3‐ and 4‐allyltoluenes in the ratio 54:10:36. By the introduction of 14C‐, D‐ and methyl labelled dienols it is shown that only the allyl group migrates and that this rearrangement is an intramolecular, one‐step process. The formation of 2‐allyltoluene occurs with retention, whereas the 3‐ and 4‐allyltoluenes are formed by inversion of the carbon skeleton of the migrating allyl group. These rearrangements can be therefore classified as suprafacial, aromatic sigmatropic reactions of the order [1,2], [3,3] and [3,4]. The transition state can be postulated as representing a positively charged complex consisting of interacting allyl and tolyl radicals. The interaction of the two parts is controlled by the symmetry of the highest occupied π‐orbitals (ψ3 for toluene and ψ2 for the allyl group) in agreement with the Woodward‐Hoffmann rules. The better “distribution” of the charge in the transition state of these reactions in comparison to the ground state is chiefly responsible for the CoPE‐like [3,3] sigmatropic reaction occurring at low temperatures. In general, sigmatropic reactions in charged systems are faster.

The rearrangement of syn and anti 2‐allyl‐2‐methylcyclohexa‐3,5‐dien‐1‐ol (syn and anti 28) gives results similar to those obtained with the para‐allyldienols.

The thermal rearrangement of 15 and 28 gives 3‐allyltoluene by a [3,3] sigmatropic Cope rearrangement followed by elimination of water.
Aza‐7‐norbornadiènes
Authors: Kitzing R. , Fuchs R. , Joyeux M. , Prinzbach H.
Published: February 2011

Several 7‐aza‐norbornadiene‐derivatives have been synthesized. Their UV.‐ and NMR.‐data are reported.
Thyrocalcitonin. II. Struktur von α‐Thyrocalcitonin
Authors: Neher R. , Riniker B. , Zuber H. , Rittel W. , Kahnt F. W.
Published: February 2011

The highly active peptide hormones isolated from pig thyroids – i.e. α‐thyrocalcitonin and its sulfoxide, containing 32 amino acid residues – were subjected to sequence studies using chemical and enzymatic methods. On the basis of these studies the following structure was derived for α‐thyrocalcitonin:

magnified image

In the α‐thyrocalcitonin sulfoxide (designated formerly as β‐thyrocalcitonin) the methionine residue is replaced by methionine sulfoxide.
Steroide und Sexualhormone: 234. Mitteilung: Synthese cis‐ständiger 1,2;4,5‐Dioxido‐3‐oxo‐ und 1,3,5‐Trihydroxyandrostane
Authors: Eggart Fr L. G. , Keller P. , Lehmann C. , Wehrli H.
Published: February 2011

The synthesis of the two stereoisomeric diepoxyketones 9 and 22, and of the tetrols 7 and 20 is described. Compound 7 contains the ring‐A‐triol partial structure characterising some naturally occurring cardiac glycosides.
Synthèse par la méthode de Merrifield d'un octapeptide faisant partie du lysozyme de blanc d' œuf de Poule (enchaǐnement Cys64 → Gly71)
Authors: Jollès Pierre , Jollès Jacqueline
Published: February 2011

The solid‐phase peptide synthesis of an octapeptide contained in hen egg‐white lysozyme (sequence Cys (residue 64) to Gly (residue 71)) is reported. Each step of the synthesis was verified by amino acid analysis. Three main reaction products were obtained. The octapeptide (50% of the reaction products) was purified by two chromatographies on Dowex 50 × 2. The purified peptide was digested by an aminopeptidase and degradated by means of Edman' s method; this latter procedure has shown that the purified octapeptide still contained around 10% of a shorter peptide.
Temperaturverhalten des Circulardichroismus und Konformationsanalyse einiger nichtkonjungierter ungesättigter Oxoverbindungen, und auf dem Steroid‐Symposium in Mailand, Mai 1966
Authors: Snatzke G. , Schaffner K.
Published: February 2011

– The circular dichroism of some non‐conjugated unsaturated carbonyl compounds, which are conformationally mobile, has been measured at +20° and at about −178°. Specifically for the steroidal compounds 1 and 2 and the monocyclic aldehyde 14, their substituted analogs 4–6, 9–11, and 15–19, respectively, as well as for the aliphatic ketone 21 the CD. temperature gradients are interpreted in terms of the preferred conformations. In the case of the β,γ‐unsaturated aldehydes 1 and 14, a correlation of these results with the photolytic decarbonylation from the excited singlet states is discussed.
Prolonged expression of the γ‐H2AX DNA repair biomarker correlates with excess acute and chronic toxicity from radiotherapy treatment
Authors: Bourton Emma C. , Plowman Piers N. , Smith Daniel , Arlett Colin F. , Parris Christopher N.
Published: February 2011

The normal tissue tolerance levels to fractionated radiotherapy have been appreciated by a century of careful clinical observations and radiobiological studies in animals. During clinical fractionated radiotherapy, these normal tissue tolerance levels are respected, and severe sequelae of radiotherapy are avoided in the majority of patients. Notwithstanding, a minority of patients experience unexpectedly severe normal tissue reactions. The ability to predict which patients might form this minority would be important. We have conducted a study to develop a rapid and reliable diagnostic test to predict excessive normal tissue toxicity (NTT) in radiotherapy patients. A flow cytometric immunocytochemical assay was used to measure DNA damage in peripheral blood lymphocytes (PBL) from cancer patients exposed to 2‐Gy gamma radiation. DNA damage and repair was measured by induction of cellular γ‐H2AX in unirradiated and exposed cells at specific time points following exposure. In 12 cancer patients that experienced severe atypical NTT following radiotherapy, there was a failure to repair DNA double‐strand breaks (DSB) as measured by γ‐H2AX induction and persistence. In ten cancer patients that experienced little or no NTT and in seven normal (noncancer controls), efficient repair of DNA DSB was observed in the γ‐H2AX assay. We conclude that a flow cytometric assay based on γ‐H2AX induction in PBL of radiotherapy patients may represent a robust, rapid and reliable biomarker to predict NTT during radiotherapy. Further research is required with a larger patient cohort to validate this important study.
Endothelin‐1 stimulates motility of head and neck squamous carcinoma cells by promoting stromal–epithelial interactions
Authors: Hinsley Emma E. , Hunt Stuart , Hunter Keith D. , Whawell Simon A. , Lambert Daniel W.
Published: February 2011

The invasion and migration of cancer cells is increasingly recognised to be influenced by factors derived from adjacent tumour‐associated stroma. The contextual signals regulating stromal–tumour interactions, however, remain poorly understood. Here, we identify a role for endothelin‐1 (ET‐1), a mitogenic peptide elevated in a number of malignancies, in promoting pro‐metastatic cross‐talk between head and neck cancer cells and adjacent fibroblasts. We demonstrate that treatment of oral fibroblasts with ET‐1 activates ADAM17‐mediated release of epidermal growth factor receptor (EGFR) ligands, triggering EGFR signalling and increased motility in neighbouring head and neck cancer cells. ET‐1–mediated paracrine transactivation of EGFR also increased cyclo‐oxygenase‐2 levels in the cancer cells, providing a molecular insight into the mechanisms by which the elevated levels of ET‐1 observed in head and neck cancers may contribute to disease progression.
Monocytes enhance cell proliferation and LMP1 expression of nasal natural killer/T‐cell lymphoma cells by cell contact‐dependent interaction through membrane‐bound IL‐15
Authors: Ishii Hideyuki , Takahara Miki , Nagato Toshihiro , Kis Loránd L. , Nagy Noémi , Kishibe Kan , Harabuchi Yasuaki , Klein Eva
Published: February 2011

Nasal natural killer (NK)/T‐cell lymphoma (NNKTL) is an Epstein‐Barr virus (EBV)‐related malignancy with poor prognosis and has distinct histological features characterized by angiocentric and polymorphous lymphoreticular infiltrates including inflammatory cells such as granulocytes, monocytes, macrophages and lymphocytes. Here, we show that the monocytes enhance proliferation as well as LMP1 expression of NNKTL cells by cell contact‐dependent interaction through membrane‐bound interleukin (IL)‐15. We used two EBV‐positive NK‐cell lines, SNK6 and KAI3, which originated from two patients—SNK6 from a patient with NNKTL and KAI3 from a patient with a severe mosquito allergy. We cocultured the cell lines with granulocytes or monocytes and examined whether proliferation, survival and LMP1 expression of the cells changed. Although cocultured granulocytes did not affect proliferation, survival or LMP1 expression of the cells, cocultured monocytes enhanced both proliferation and LMP1 expression in a dose‐dependent manner. These phenomena were not seen when monocytes were placed in a separate chamber. Moreover, the monocyte‐inducible proliferation and LMP1 expression were inhibited by treatment with an antibody against IL‐15. Furthermore, production of interferon‐gamma‐inducible protein (IP)‐10 were enhanced by coculture with monocytes and were inhibited by the antibody. Immunohistological studies confirmed that a number of infiltrating CD14‐positive monocytes contacted CD56‐positive lymphoma cells in all of 20 NNKTL tissues tested. These results suggest that monocytes enhance cell growth as well as LMP1 expression of NNKTL cells by cell contact‐dependent interaction through membrane‐bound IL‐15. In the microenvironment of NNKTL tissue, a positive feedback loop of interaction between lymphoma cells and monocytes may be present and contribute to lymphoma progression.
Tumor suppressor dual‐specificity phosphatase 6 (DUSP6) impairs cell invasion and epithelial‐mesenchymal transition (EMT)‐associated phenotype
Authors: Wong Victor Chun Lam , Chen Han , Ko Josephine Mun Yee , Chan Kwok Wah , Chan Yuen Piu , Law Simon , Chua Daniel , Kwong Dora Lai‐Wan , Lung Hong Lok , Srivastava Gopesh , Tang Johnny Cheuk On , Tsao Sai Wah , Zabarovsky Eugene R. , Stanbridge Eric J. , Lung Maria Li
Published: February 2011

Suppressive effects of DUSP6 in tumorigenesis and EMT‐associated properties were observed. Dual‐specificity phosphatase (DUSP6) is a MAP kinase phosphatase (MKP) negatively regulating the activity of ERK, one of the major molecular switches in the MAPK signaling cascade propagating the signaling responses during malignancies. The impact of DUSP6 in EMT and its contribution to tumor dissemination has not yet been characterized. Due to differences in tumor microenvironments affecting cell signaling during cancer progression, DUSP6 may play varying roles in tumor development. We sought to examine the potential role of DUSP6‐mediated tumorigenesis and EMT‐associated properties in two aerodigestive tract cancers, namely, esophageal squamous cell carcinoma (ESCC) and nasopharyngeal carcinoma (NPC). Significant loss of DUSP6 was observed in 100% of 11 ESCC cell lines and 71% of seven NPC cell lines. DUSP6 expression was down‐regulated in 40% of 30 ESCC tumor tissues and 75% of 20 NPC tumor tissues compared to their respective normal counterparts. Suppressive effects of DUSP6 in tumor formation and cancer cell mobility are seen in in vivo tumorigenicity assay and in vitro colony formation, three‐dimensional Matrigel culture, cell migration and invasion chamber tests. Notably, overexpression of DUSP6 impairs EMT‐associated properties. Furthermore, tissue microarray analysis reveals a clinical association of DUSP6 expression with better patient survival. Taken together, our study provides a novel insight into understanding the functional impact of DUSP6 in tumorigenesis and metastasis of ESCC and NPC.
Parenteral is more efficient than mucosal immunization to induce regression of human papillomavirus‐associated genital tumors
Authors: Decrausaz Loane , Domingos‐Pereira Sonia , Duc Mélanie , Bobst Martine , Romero Pedro , Schiller John T. , Jichlinski Patrice , Nardelli‐Haefliger Denise
Published: February 2011

Cervical cancer is a public health concern as it represents the second cause of cancer death in women worldwide. High‐risk human papillomaviruses (HPV) are the etiologic agents, and HPV E6 and/or E7 oncogene‐specific therapeutic vaccines are under development to treat HPV‐related lesions in women. Whether the use of mucosal routes of immunization may be preferable for inducing cell‐mediated immune responses able to eradicate genital tumors is still debated because of the uniqueness of the female genital mucosa (GM) and the limited experimentation. Here, we compared the protective activity resulting from immunization of mice via intranasal (i.n.), intravaginal (IVAG) or subcutaneous (s.c.) routes with an adjuvanted HPV type 16 E7 polypeptide vaccine. Our data show that s.c. and i.n. immunizations elicited similar frequencies and avidity of TetE7+CD8+ and E7‐specific Interferon‐gamma‐secreting cells in the GM, whereas slightly lower immune responses were induced by IVAG immunization. In a novel orthotopic murine model, both s.c. and i.n. immunizations allowed for complete long‐term protection against genital E7‐expressing tumor challenge. However, only s.c. immunization induced complete regression of already established genital tumors. This suggests that the higher E7‐specific systemic response observed after s.c. immunization may contribute to the regression of growing genital tumors, whereas local immune responses may be sufficient to impede genital challenges. Thus, our data show that for an efficiently adjuvanted protein‐based vaccine, parenteral vaccination route is superior to mucosal vaccination route for inducing regression of established genital tumors in a murine model of HPV‐associated genital cancer.
A feedback loop between BEX2 and ErbB2 mediated by c‐Jun signaling in breast cancer
Authors: Naderi Ali , Liu Ji , Francis Glenn D.
Published: February 2011

BEX2 is a member of brain expressed X‐linked gene family that is differentially expressed in primary breast tumors. We have previously demonstrated that BEX2 expression protects breast cancer cells against mitochondrial apoptosis and G1 cell cycle arrest. In addition, we have shown that BEX2 is a c‐Jun target gene and, in turn, regulates the phosphorylation of c‐Jun in breast cancer cells. In our study, we investigated BEX2 protein expression in a tissue microarray cohort of 225 breast tissue samples with known clinical, pathological and biomarker information. We observed that BEX2 protein was overexpressed in ∼50% of malignant breast tumors compared to only 7% of benign breast samples. Notably, BEX2 positive tumors identified a subset of breast cancers with the overexpression of ErbB2 and phosphorylated c‐Jun proteins. Furthermore, using in vitro models, we demonstrated that the mechanism of this association is a functional feedback loop involving ErbB2, c‐Jun and BEX2 in breast cancer cells. In this feedback loop, ErbB2 overexpression results in an induction of c‐Jun and BEX2 expression. Importantly, ErbB2 induction of BEX2 expression was abrogated by a dominant‐negative mutant of c‐Jun, suggesting that this effect was mediated through the regulation of c‐Jun signaling. In turn, the overexpression of BEX2 led to an increase in both c‐Jun–mediated induction of ErbB2 and c‐Jun binding to the ErbB2 promoter in MCF‐7 cells. Our study suggests that BEX2 protein is overexpressed in approximately half of breast cancers and has a positive feedback loop with ErbB2 mediated by c‐Jun signaling in breast cancer cells.
Nanoscale Digital Devices Based on the Photoelectrochemical Photocurrent Switching Effect: Preparation, Properties and Applications
Authors: Gawęda Sylwia , Kowalik Remigiusz , Kwolek Przemysław , Macyk Wojciech , Mech Justyna , Oszajca Marek , Podborska Agnieszka , Szaciłowski Konrad
Published: February 2011

New materials and new phenomena which can be used for information processing always inspire great enthusiasm. On the other hand, silicon is still the main workhorse of modern electronics. Production of bulk quantities of ultrapure silicon is relatively cheap and the processing technologies are extremely sophisticated. Introduction of new materials and phenomena, on the other hand, requires an enormous amount of hard experimental and theoretical work. The photoelectrochemical photocurrent switching effect (PEPS) is one of the processes that, in principle, can evolve into new information processing technology. This review presents the effect itself, along with preparation of appropriate semiconducting materials, physical principles of semiconductor–molecule interactions, and finally some prototypical constructions of logic devices based on the PEPS effect.
Biologically Relevant Molecular Finite Automata
Authors: Shoshani Sivan , Ratner Tamar , Piran Ron , Keinan Ehud
Published: February 2011

Bio‐Molecular Computing (BMC) has been rapidly evolving as an independent field at the interface between computer science, mathematics, chemistry, and biology. Over the years, numerous architectures of autonomous molecular computing devices have been developed in the lab on the basis of opportunities offered by molecular biology techniques. This account focuses mainly on the realization of programmable DNA‐based finite‐state automata that can compute autonomously upon mixing all their components in solution.The main advantage of autonomous BMC devices over electronic computers arises from their ability to interact directly with biological systems and even with living organisms without any interface. Indeed, it has been demonstrated that appropriately designed computing machines can produce output signals in the form of a specific biological function via direct interaction with living cells. Additional topics are briefly included to point at interesting opportunities in the field and to describe some of the potential applications and extension of the basic concepts. These include logic evaluators and logic gates that operate in cells, applications in developmental biology, as well as chemical encoding and processing of alphanumeric information.
Fiscal activism and the cost of debt financing
Authors: Dewachter Hans , Toffano Priscilla
Published: February 2011

In this paper, we estimate the impact of changes in fiscal policy regime on the yield curve. In particular, we differentiate between yield curve responses under active and passive fiscal policy regimes (according to the terminology of Leeper (1991)). Analyzing US data in the period 1965–2010, we find a statistically significant impact of fiscal policy only for the active policy regime. A one‐percentage point shock in the primary deficit leads typically to a contemporaneous increase in long‐term yields of about 10 basis points, and even stronger cumulative effects. No significant impact of deficits on yields is found in the passive fiscal policy regime. Copyright © 2011 John Wiley & Sons, Ltd.
Improving irrigation water operation in the lower reaches of the Amu Darya River – current status and suggestions
Authors: Awan Usman Khalid , Ibrakhimov Mirzakhayot , Tischbein Bernhard , Kamalov Pulat , Martius Christopher , Lamers John P.A.
Published: February 2011

Irrigated agriculture is widespread in the Central Asian drylands and important for food security of the region. However irrigation practices based on rules made for cotton production on large units do not provide adequate guidance for the now widespread small farms that produce cotton wheat and rice. Excessive unsustainable water use is the consequence. Land and water resource management practices were analysed in 2006 for the irrigated area (approx. 1885 ha) of a water users' association (WUA) as a case study. The Shomakhulum WUA is situated in the Khorezm region Uzbekistan in the Aral Sea Basin. The designed water allowance of 0.40 l s−1 ha−1 was 46% higher than the 0.21 l s−1 ha−1 required in 2006. A ponding experiment conducted at two locations under typically shallow groundwater conditions showed that actual seepage losses in the major distributing canal (Pakhtakiyar) in the WUA were about 2% at one site and negative at the other. This does not support the present blanket recommendation of an additional 29% of water to compensate for anticipated seepage losses. Considering the effects of shallow groundwater the seasonal leaching requirements were estimated at 200 mm versus the 400 mm based on the blanket local recommendations for a 14 ha cotton field. However the actually applied water amounted to 670 mm which exceeds the calculated requirements by 235% and the local recommendation by 68%. The findings showed (i) excessive irrigation water supply and in turn high wastage owing to an underestimation of the potential shallow groundwater contribution (ii) overestimation of conveyance losses and (iii) excessive leaching due to outdated knowledge on leaching requirements when compared to standards. We suggest that the outdated water allowance the inaccurate estimation of the conveyance efficiency and excessive water applications during leaching cause a waste of precious fresh water and a rise in the shallow groundwater levels which consequently increases secondary soil salinity. The revision of irrigation and leaching norms combined with an improved knowledge on seepage dynamics under shallow groundwater levels is needed before any further recommendations can be made to the farmers in order to reach the objective of sustainable agriculture in the area. Copyright © 2011 John Wiley & Sons Ltd.
Evaluation of modified DRAINMOD in predicting groundwater table fluctuations and yield of canola in paddy fields under snowy conditions (case study: Rasht Iran)
Authors: Hassanpour B. , Parsinejad M. , Yazdani M.R. , Dalivand F. Salahshour , Kossari H.
Published: February 2011

The computer simulation hydrologic model DRAINMOD and modified DRAINMOD (Luo et al. 2000) for cold condition was used to predict the performance of surface drainage and yield of canola as post‐rice cultivation during the wet growing season of 2004–2005 in Rasht Iran.

Performance of surface drainage system treatments with 2 m spacing and 15 cm drain depth as compared with plots having no drainage (4 × 10 m2) were used to evaluate the models. Evaluation of predicted daily groundwater table depths as compared with measured values shows that the root mean square error (RMSE) was about 10.2 and 9.9 cm for DRAINMOD versus 11.0 and 11.5 for modified DRAINMOD in 2 m drain spacing and no drainage treatment respectively. Original DRAINMOD and modified DRAINMOD predictions for groundwater table depth was on average about 4 and 7% less than measured values for the surface drainage treatment and 22 and 14% greater for the no drainage treatment whereas the standard error of original DRAINMOD was 1.4 and 1.51 (cm) respectively. The average absolute deviations were 8.67 and 9.22 (cm). However by using the modified DRAINMOD these values were decreased to 1.34 1.3 8.05 and 8.19 cm respectively.

Comparisons show that modifications introduced in DRAINMOD for snowy conditions improved the capability of the model to predict groundwater table fluctuations. Copyright © 2011 John Wiley & Sons Ltd.
Interferon-γ plays a role in bone formation in vivo and rescues osteoporosis in ovariectomized mice
Authors: Duque Gustavo , Huang Dao Chao , Dion Natalie , Macoritto Michael , Rivas Daniel , Li Wei , Yang Xian Fang , Li Jiarong , Lian Jing , Marino Faleh Tamim , Barralet Jake , Lascau Viorica , Deschênes Claire , Ste-Marie Louis-Georges , Kremer Richard
Published: February 2011

Interferon γ (IFN-γ) is a cytokine produced locally in the bone microenvironment by cells of immune origin as well as mesenchymal stem cells. However, its role in normal bone remodeling is still poorly understood. In this study we first examined the consequences of IFN-γ ablation in vivo in C57BL/6 mice expressing the IFN-γ receptor knockout phenotype (IFNγR1−/−). Compared with their wild-type littermates (IFNγR1+/+), IFNγR1−/− mice exhibit a reduction in bone volume associated with significant changes in cortical and trabecular structural parameters characteristic of an osteoporotic phenotype. Bone histomorphometry of IFNγR1−/− mice showed a low-bone-turnover pattern with a decrease in bone formation, a significant reduction in osteoblast and osteoclast numbers, and a reduction in circulating levels of bone-formation and bone-resorption markers. Furthermore, administration of IFN-γ (2000 and 10,000 units) to wild-type C57BL/6 sham-operated (SHAM) and ovariectomized (OVX) female mice significantly improved bone mass and microarchitecture, mechanical properties of bone, and the ratio between bone formation and bone resorption in SHAM mice and rescued osteoporosis in OVX mice. These data therefore support an important physiologic role for IFN-γ signaling as a potential new anabolic therapeutic target for osteoporosis. © 2011 American Society for Bone and Mineral Research.
The effectiveness of a trauma focused spiritually integrated intervention for veterans exposed to trauma
Authors: Harris J. Irene , Erbes Christopher R. , Engdahl Brian E. , Thuras Paul , Murray‐Swank Nichole , Grace Dixie , Ogden Henry , Olson Raymond H.A. , Winskowski Ann Marie , Bacon Russ , Malec Catherine , Campion Kelsey , Le TuVan
Published: February 2011

Building Spiritual Strength (BSS) is an 8‐session, spiritually integrated group intervention designed to address religious strain and enhance religious meaning making for military trauma survivors. It is based upon empirical research on the relationship between spirituality and adjustment to trauma. To assess the intervention's effectiveness, veterans with histories of trauma who volunteered for the study were randomly assigned to a BSS group (n = 26) or a wait‐list control group (n = 28). BSS participants showed statistically significant reductions in PTSD symptoms based on self‐report measures as compared with those in a wait‐list control condition. Further research on spiritually integrated interventions for trauma survivors is warranted. © 2011 Wiley Periodicals, Inc. J Clin Psychol 67:1–14, 2011.
Advantages of modal decomposition for efficient scaling of parallel FDTD computations
Authors: Gorodetsky Dmitry A. , Wilsey Philip A.
Published: February 2011

When a scheme such as FDTD is used to perform full‐wave electromagnetic simulation of electrically large objects, it can result in excessive computation times. Parallel processing is one means to reduce the computation time. A shortcoming of the parallel approach is the communication overhead that is responsible for reduced speedup efficiency but inevitable at every time step. An alternative to reduce the communication is to look at FDTD from the modal analysis point of view. With modal analysis we can gain some very useful insights into the operation of the algorithm, which we pay for with a relatively expensive setup time. We consider parallelizing the modal analysis algorithm with transient and steady‐state excitation scenarios. Copyright © 2011 John Wiley & Sons, Ltd.
Orbital imprint on Holocene palaeohydrological variations in west‐central Europe as reflected by lake‐level changes at Cerin (Jura Mountains, eastern France)
Authors: Magny Michel , Bossuet Gilles , Ruffaldi Pascale , Leroux Aurélie , Mouthon Jacques
Published: February 2011

This paper presents a lake‐level record for the Holocene at Lake Cerin (Jura Mountains, eastern France). It is based on a range of sedimentological techniques validated in previous studies, with a combination of systematic lithostratigraphic investigations of the infillings accumulated in the lacustrine basin, and sediment analyses of two selected cores. The chronology is based on 10 radiocarbon dates and pollen stratigraphy. On a millennial scale, the Cerin lake‐level record shows three distinct successive phases characterised by higher lake‐level conditions until ca. 9000 cal. a BP, followed by a maximal lowering at ca. 9000–8500 cal. a BP, and a progressive rise until the present. This rise was punctuated by centennial‐scale fluctuations, with major events around 4000, 2800 and after 1500 cal. a BP. Considered on a multimillennial scale, the general pattern of palaeohydrological changes reconstructed at Cerin reflects the impact of orbitally driven summer insolation. This is in agreement with other regional and extra‐regional palaeoclimatic records, although every record shows peculiarities in timing and shape depending on the proxy used for reconstruction. In this general context, centennial to multicentennial oscillations appear to have been second‐order events in comparison with the major influence of the orbital factor. Copyright © 2011 John Wiley & Sons, Ltd.
Holocene sea‐level reconstruction in the Young Sound region, Northeast Greenland
Authors: Pedersen Jørn Bjarke Torp , Kroon Aart , Jakobsen Bjarne Holm
Published: February 2011

A relative sea‐level curve over the Holocene is constructed for the Young Sound region in northeastern Greenland. The reconstruction is derived by dating the heights of raised beach ridges in coastal plains using optically stimulated luminiscence (OSL), and by dating palaeoterrestrial surface levels now buried beneath the intertidal frame using the14C technique. The relative sea‐level curve reveals a rapid fall of at least 10 mm a−1from ca. 9500 to 7500 a ago, which slowed to 2 mm a−1until it reached the present sea level ca. 3000 a ago. This part of the curve is based on the raised beach ridge data. Thereafter, relative sea level continued to fall, to reach a minimum level at about 0.5 m below the present sea level ca. 2300 a ago. Since then, relative sea level has experienced a slow rise of about 0.2 mm a−1. This part of the curve uses the data from the palaeoterrestrial surfaces. The study supplements other estimates of Holocene relative sea‐level changes and supports the observations of a decreasing trend in the timing of the cross point and in minimum relative sea level from South to North Greenland. Copyright © 2011 John Wiley & Sons, Ltd.
Glaciers and climate in Pacific Far NE Russia during the Last Glacial Maximum
Authors: Barr Iestyn D. , Clark Chris D.
Published: February 2011

A combined geomorphological–physical model approach is used to generate three‐dimensional reconstructions of glaciers in Pacific Far NE Russia during the global Last glacial Maximum (gLGM). The horizontal dimensions of these ice masses are delineated by moraines, their surface elevations are estimated using an iterative flowline model and temporal constraints upon their margins are derived from published age estimates. The equilibrium line altitudes (ELAs) of these ice masses are estimated, and gLGM climate is reconstructed using a simple degree–day melt model. The results indicate that, during the gLGM, ice masses occupying the Pekulney, Kankaren and Sredinny mountains of Pacific Far NE Russia were of valley glacier and ice field type. These glaciers were between 7 and 80 km in length, and were considerably less extensive than during pre‐LGM phases of advance. gLGM ice masses in these regions had ELAs of between 575 ± 22 m and 1035 ± 41 m (above sea level) – corresponding to an ELA depression of 350–740 m, relative to present. Data indicate that, in the Pekulney Mountains, this ELA depression occurred because of a 6.4°C reduction in mean July temperature, and 200 mm a−1 reduction in precipitation, relative to present. Thus reconstructions support a restricted view of gLGM glaciation in Pacific Far NE Russia and indicate that the region's aridity precluded the development of large continental ice sheets. Copyright © 2011 John Wiley & Sons, Ltd.
Can lymphatic drainage of head and neck melanoma be predicted?
Authors: Jensen Jesse D. , Gray Richard J. , Wasif Nabil , Roarke Michael C. , Casey William J. , Kreymerman Peter , Pockaj Barbara A.
Published: February 2011

Background

The lymphatic drainage patterns of the head and neck (H&N) is complex. Therefore, identification of the sentinel lymph node (SLN) for H&N melanoma can be challenging.

Methods

Retrospective review of a prospectively collected melanoma database, from February 1997 through October 2008, identified 137 patients with H&N melanoma. All underwent pre‐operative lymphoscintigraphy, and after 2007, patients underwent single photon emission computed tomography combined with computed tomography (SPECT/CT).

Results

The mean number of SLNs per patient was 2.6. An SLN was successfully identified in 97% of patients, and in 9%, the SLN was positive for metastatic disease. The majority of patients (88%) drained to a unilateral level. Bilateral drainage occurred in 10%, with only two patients draining outside of the neck. The majority of patients (58%) had an SLN in level IIa (jugulodigastric lymph nodes). The regional recurrence rate was 4%, which all occurred prior to the use of SPECT/CT.

Discussion

Utilization of SPECT/CT and knowledge of common lymphatic drainage patterns in neck lymph node levels can assist the surgeon in properly locating and excising the SLN with minimal morbidity, limiting unnecessary dissections, as well as reducing false negative results. J. Surg. Oncol. 2011;103:751–755. © 2011 Wiley‐Liss, Inc.
Distinctive effects of plant protein sources on renal disease progression and associated cardiac hypertrophy in experimental kidney disease
Authors: Aukema Harold M. , Gauthier Joy , Roy Manon , Jia Yong , Li Huan , Aluko Rotimi E.
Published: February 2011

Scope: Dietary soy protein reduces renal disease progression in a number of renal diseases, suggesting that plant compared with animal proteins may be renoprotective. The inclusion of other plant protein sources could enhance compliance of intervention diets, but the effects of other plant protein sources are not known.

Methods and results: Weanling Han:SPRD‐cy rats with experimental polycystic kidney disease were given hemp‐, pea‐ and soy protein‐based diets compared with the standard AIN 93G diet with casein as the protein source. Kidneys from diseased rats given diets which contained soy or hemp protein compared with casein‐based diets were less enlarged, had lower fluid content, smaller cyst volumes, less fibrosis, lower chemokine receptor 2 (CCR2) levels and normalized serum creatinine levels. Soy and hemp protein diets also normalized heart size, which was enlarged in diseased compared with normal rats consuming casein. Kidneys from diseased rats given pea protein compared with casein were more enlarged and had higher fluid content and cyst volumes, despite growing better and having lower serum creatinine and renal chemokine receptor 2 levels, and similar levels of renal fibrosis.

Conclusion: Not all plant proteins are equally protective in experimental kidney disease and associated cardiac hypertrophy.
Quantitative proton MR spectroscopic imaging of the human brain
Authors: Soher Brian J. , van Zijl Peter C. M. , Duyn Jeffrey H. , Barker Peter B.
Published: February 2011

Multislice proton MR spectroscopic images (SI) of the brain were quantitated, using the phantom replacement technique. In 16 normal volunteers, ranging in age from 5 to 74 years, average “whole brain” concentrations of choline (Cho), creatine (Cr), and N‐acetylaspartate (NAA) were found to be 2.4 ± 0.4, 7.9 ± 1.3, and 11.8 ± 1.0 (mM, mean ± SD), respectively. These values are in good general agreement with those previously determined by single‐voxel localization techniques. Cortical gray matter was found to have lower Cho and NAA levels, compared to those of white matter, corpus callosum, and basal ganglia. Cho was also found to increase significantly with age in several locations. Quantitative multislice proton SI is feasible in the clinical environment, and regional and age‐dependent variations occur that must be accounted for when evaluating spectra from pathological conditions.
New method for contrast manipulation in DNP‐enhanced MRI
Authors: Planinšič Gorazd , Grucker Daniel , Stepišnik Janez
Published: February 2011

The magnetization subtraction technique (MS), which is equivalent to the inversion recovery technique in strong magnetic fields, has been implemented in dynamic nuclear polarization‐enhanced magnetic resonance imaging (DNPI). The general theoretical basis of the MS method, which can be applied to DNPI or to prepolarized MRI in weak magnetic fields (such as Earth's magnetic field), is introduced. Details are provided about the signal amplitude, dynamic range of the method, and conditions required to observe signal void in samples with specific T1 relaxation times. The experimental results obtained with MS DNPI are presented and discussed. In the experiments, electron spin resonance irradiation frequencies of 199 MHz and 16.2 MHz were employed. Also, T1 contrast manipulation in the polarizing and in the detection magnetic field is discussed and demonstrated for MS DNPI.