bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical Bragg imaging of acoustic fields after reflection
Authors: Declercq Nico F. , McPherson Michael S. , Breazeale Mack A. , Teklu Alem A.
Published: June 2010

Bragg diffraction of x-rays occurs when the rays interact with a crystalline lattice at the appropriate angle. Bragg diffraction of visible light occurs when the light interacts at the Bragg angle with an ultrasonic field of the appropriate frequency. (The spacing between acoustic condensations and rarefactions acts like the planes in an atomic lattice.) If a beam of light is Bragg diffracted by an ultrasonic beam that previously has passed through an object, an image of the structure of the object is made visible in the diffraction field of the optical beam since there is a one-to-one mapping of the ultrasonic field onto the diffraction order. In many acoustic Bragg imaging applications, the sound field must pass through the object which is to be imaged. Ultrasonic attenuation at the very high acoustic frequencies needed for Bragg imaging (typically ∼25–30 MHz) severely limits the nondestructive testing (NDT) applications of traditional acoustic Bragg imaging. In this paper, a reflection-based application of acoustic Bragg imaging is discussed which may have useful industrial and biomedical NDT applications.
Target distance-dependent variation of hearing sensitivity during echolocation in a false killer whale
Authors: Supin Alexander Ya. , Nachtigall Paul E. , Breese Marlee
Published: June 2010

Evidence of varying hearing sensitivity according to the target distance was obtained in a false killer whale Pseudorca crassidens during echolocation. Auditory evoked potentials (AEPs) triggered by echolocation clicks were recorded. The target distance varied from 1 to 6 m. The records contained AEPs to the self-heard emitted click and AEPs to the echoes. Mean level of echolocation clicks depended on distance (the longer the distance, the higher the click level), however, the effect of click level on AEP amplitude was eliminated by extracting AEPs to clicks of certain particular levels. The amplitude of the echo-provoked AEP was almost independent of distance, however, the amplitude of the AEP to the emitted click, did depend on distance within a range from 1 to 4 m: the longer the distance, the higher the amplitude. The latter result is interpreted as confirmational evidence that the animal is capable of varying hearing sensitivity according to target distance. The variation of hearing sensitivity may help to compensate for the echo attenuation with distance; as a secondary effect, this variation manifested itself in a variation of the amplitude of the AEP to emitted clicks.
Thermoacoustic properties of fibrous materials
Authors: Jensen Carl , Raspet Richard
Published: June 2010

The thermoacoustic properties of fibrous materials are studied using a computational fluid simulation as a test of proposed analytical models for propagation in porous materials with an ambient temperature gradient. The acoustic properties of porous materials have been understood in terms of microstructural models that approximate the material as an array of pores with empirical shape factors used to fit the pore theory to the material. An extension of these theories of acoustics to the thermoacoustic case with an ambient temperature gradient has been proposed by Roh et al. [J. Acoust. Soc. Am. 121, 1413–1422 (2007)] and a model based on Wilson’s relaxation approximation for porous acoustics [J. Acoust. Soc. Am. 94, 1136–1145 (1993)] is proposed herein, but the predictions of these analytical models have not been tested successfully against measurements. Accurately characterizing the effects of the applied temperature gradient in a wide bandwidth laboratory setup have proven difficult; as a result, the authors conducted a numerical simulation of propagation within a fibrous geometry in order to test the predictions of the analytical models. The results for several fibrous samples show that the models yield a reliable prediction of thermoacoustic performance from the shape factors and relaxation times.
Acoustic emission monitoring of degradation of cross ply laminates
Authors: Aggelis D. G. , Barkoula N. M. , Matikas T. E. , Paipetis A. S.
Published: June 2010

The scope of this study is to relate the acoustic activity of damage in composites to the failure mechanisms associated with these materials. Cross ply fiber reinforced composites were subjected to tensile loading with recording of their acoustic activity. Acoustic emission (AE) parameters were employed to monitor the transition of the damage mechanism from transverse cracking (mode I) to delamination (mode II). Wave propagation measurements in between loading steps revealed an increase in the relative amplitude of the propagated wave, which was attributed to the development of delamination that confined the wave to the top longitudinal plies of the composite.
Biostratigraphic constraints and depositional environment of theLower Cretaceous (Albian) Boulder Creek Formation, Monkman area, northeastern British Columbia
Authors: Stelck C. R. , Leckie Dale A.
Published: June 2010

A full core through the Boulder Creek Formation in the Monkman area of northeastern British Columbia yielded foraminifera from the overlying Hasler Formation and underlying Hulcross Formation, thereby constraining the age of the Boulder Creek Formation from mid middle Albian to mid late Albian. Shales of the Hulcross Formation carry the microfauna of the Haplophragmoides multiplum Subzone of the Gaudryina nanushukensis Zone. Cored shales of the Hasler Formation immediately overlying the Boulder Creek Formation carry the microfauna of the Trochammina depressa Subzone of the Haplophragmoides gigas Zone. The presence of 15 fossil soils within the middle portion of the Boulder Creek Formation records multiple depositional hiatuses within the formation in the Monkman area.
Lower Permian "mecopteroid-like" insects from central Europe (Insecta, Endopterygota)
Authors: Kukalova-Peck Jarmila , Willmann Rainer
Published: June 2010

Five new genera and eight new species of endopterygote insects are described from Lower Permian (Asselian and Artinskian) strata from Moravia, Czechoslovakia. Three of the genera belong to the family Protomeropidae: Pseudomerope n.gen. (including Pseudomerope mareki n.sp., Pseudomerope havlati n.sp., Pseudomerope oborana n.sp., Pseudomerope gallei n.sp.); Pseudomeropella n.gen. (including Pseudomeropella nekvasilovae n.sp.); and Stenomerope n.gen. (including Stenomerope spinari n.sp.). The fourth genus, Moravochorista n.gen. (including Moravochorista Carolina n.sp.), is similar to Pinnachorista and Kaltanochorista from the Lower Permian of the Kuznetsk Basin, USSR, but has not been assigned to a higher taxon. The phylogenetic position of both the Protomeropidae and Moravochorista and of their allies, within the endopterygotes is unclear. The fifth genus, Microptysmella n.gen. (including Microptysmella moravica n.sp.), may be the earliest known member of Amphiesmenoptera, since it exhibits almost the same wing venation as the amphiesmenopteran Microptysma sibiricum Martynova from the Lower Permian of the USSR.Wing-venation symbols homologous within the pterygote ground plan have been used in the descriptions. The vein "M5" of earlier authors is regarded as homologous to a convex cross-vein (strut) between the media posterior and the cubitus anterior, which is shared primitively by all endopterygotes, and is not a "fifth medial branch."
Fluvially sculpted rock bedforms in Twenty Mile Creek, Niagara Peninsula, Ontario
Authors: Tinkler K. J.
Published: June 2010

Sculpted rock bedforms (s-forms) on Whirlpool Sandstone are described from the bed of Twenty Mile Creek. The morphologies identified (undulating surfaces, rises, furrows, comma forms, spindles, potholes, and transverse troughs) are those described for sculpted bedrock forms (p-forms, s-forms) developed in subglacial environments. Additional morphologies identified are undercut downsteps and quarried surfaces in the lee of bedrock rises. Morphological differences between the subglacial and fluvial forms are attributed to the difference between confined conduit flow in the subglacial case and open-channel flow in the fluvial examples. In fluvial systems the descending bedrock surface presents rock differently to oncoming flows and favours certain s-forms (quarried lee faces and undulating surfaces). In a strong-flow fluvial environment s-forms develop by wear. Dominant sediment-transport modes are large clasts (up to metre dimensions) and suspended silt–clay with a small (< 7%) hard or heavy-mineral component. Hydraulic quarrying, which removes fracture-delimited blocks from the bed, interrupts the process. Although fluvial s-forms are similar to subglacial s-forms, large stable vortices may not exist in the fluvial context over the range of effective stages. Upper regime flow is common over bedrock reaches, and flow acceleration at small downsteps (knickpoints) magnifies the duration and spatial extent of wear effective velocities.
Monazite as a metamorphic chronometer, south of the Grenville Front, western Quebec
Authors: Childe Fiona , Doig Ronald , Gariépy Clément
Published: June 2010

Monazite was utilized as a chronometer to examine the effects of high-grade metamorphism across the Parautochthonous Belt and Allochthon Boundary Thrust of the Grenville Province in western Quebec. This study, in addition to previous geo-chronological studies, indicates an Archean component in the gneisses, which is consistent with the presence of more than one set of peak metamorphic conditions.Single-grain monazite analyses from metasedimentary gneisses from four locations within the Parautochthonous Belt yielded Grenvillian U–Pb dates of 1000 ± 5 to 1006 ± 2 Ma. The location farthest to the northwest, 45 km southeast of the Grenville Front, included monazite with a distinct Archean signature. Southeast of this point an Archean signature was not detected in the monazite. At 70 km southeast of the Grenville Front, monazite yielded two discrete ages of 1005 ± 2 and 1020 ± 3 Ma. Xenotime from one location indicated that the closure temperature of this mineral may be equivalent to that of monazite (725 ± 25 °C).Monazite from the Allochthon Boundary Thrust, 135 km southeast of the Grenville Front, yielded 207Pb/206Pb dates of 1049–1092 Ma, indicating earlier cooling than rocks closer to the Grenville Front. The monazite age was combined with that of rutile from the same location to determine a cooling rate of 2 °C/Ma following cooling through the closure temperature of monazite. The abrupt transition from Archean to Grenvillian ages some 45 km southeast of the Grenville Front is consistent with tectonic transport in the form of northwest-directed thrusting.
40Ar/39Ar age and correlation of the nonmarine Two Medicine Formation (Upper Cretaceous), northwestern Montana, U.S.A.
Authors: Rogers Raymond R. , Swisher III Carl C. , Horner John R.
Published: June 2010

The age of the nonmarine Two Medicine Formation of northwestern Montana is currently based upon correlations with K–Ar-dated Western Interior ammonite zones. 40Ar/39Ar dating of biotite and plagioclase separated from four bentonites and one crystal-rich tuff permits for the first time direct determination of the age of Two Medicine strata. Biotite and plagioclase from a bentonite 10 m below the top of the Two Medicine Formation yield concordant 40Ar/39Ar ages of 74 Ma, while biotite and plagioclase from two bentonites and a crystal-rich tuff from approximately 100 m above the base of the formation cluster in age around 80 Ma. The total duration of Two Medicine deposition is estimated using these new radio-isotopic ages via extrapolation of an average rock accumulation rate.The new 40Ar/39Ar ages facilitate regional correlation of the dinosaur-dominated paleofauna recovered from the Two Medicine Formation, and help constrain the timing of the Claggett and Bearpaw transgressions. The ages support correlation of the richly fossiliferous upper lithofacies suite of the Two Medicine Formation with exposures of the Judith River Formation in Dinosaur Provincial Park, Alberta, Canada. Radioisotopically dated exposures of the Judith River Formation within Montana that include important Judithian "age" mammal localities correlate approximately with middle and lower parts of the middle lithofacies suite of the Two Medicine Formation. The new 40Ar/39Ar ages further indicate that the transgressions of the Claggett and Bearpaw seas culminated within northwestern Montana at ca. 79.6 and 74.0 Ma, respectively.
Copper Metallochaperones
Authors: Robinson Nigel J. , Winge Dennis R.
Published: June 2010

The current state of knowledge on how copper metallochaperones support the maturation of cuproproteins is reviewed. Copper is needed within mitochondria to supply the CuA and intramembrane CuB sites of cytochrome oxidase, within the trans-Golgi network to supply secreted cuproproteins and within the cytosol to supply superoxide dismutase 1 (Sod1). Subpopulations of copper-zinc superoxide dismutase also localize to mitochondria, the secretory system, the nucleus and, in plants, the chloroplast, which also requires copper for plastocyanin. Prokaryotic cuproproteins are found in the cell membrane and in the periplasm of gram-negative bacteria. Cu(I) and Cu(II) form tight complexes with organic molecules and drive redox chemistry, which unrestrained would be destructive. Copper metallochaperones assist copper in reaching vital destinations without inflicting damage or becoming trapped in adventitious binding sites. Copper ions are specifically released from copper metallochaperones upon contact with their cognate cuproproteins and metal transfer is thought to proceed by ligand substitution.
Enzyme Promiscuity: A Mechanistic and Evolutionary Perspective
Authors: Tawfik Olga Khersonsky and Dan S.
Published: June 2010

Many, if not most, enzymes can promiscuously catalyze reactions, or act on substrates, other than those for which they evolved. Here, we discuss the structural, mechanistic, and evolutionary implications of this manifestation of infidelity of molecular recognition. We define promiscuity and related phenomena and also address their generality and physiological implications. We discuss the mechanistic enzymology of promiscuity—how enzymes, which generally exert exquisite specificity, catalyze other, and sometimes barely related, reactions. Finally, we address the hypothesis that promiscuous enzymatic activities serve as evolutionary starting points and highlight the unique evolutionary features of promiscuous enzyme functions.
Regulation of mRNA Translation and Stability by microRNAs
Authors: Fabian Marc Robert , Sonenberg Nahum , Filipowicz Witold
Published: June 2010

MicroRNAs (miRNAs) are small noncoding RNAs that extensively regulate gene expression in animals, plants, and protozoa. miRNAs function posttranscriptionally by usually base-pairing to the mRNA 3′-untranslated regions to repress protein synthesis by mechanisms that are not fully understood. In this review, we describe principles of miRNA-mRNA interactions and proteins that interact with miRNAs and function in miRNA-mediated repression. We discuss the multiple, often contradictory, mechanisms that miRNAs have been reported to use, which cause translational repression and mRNA decay. We also address the issue of cellular localization of miRNA-mediated events and a role for RNA-binding proteins in activation or relief of miRNA repression.
Protein Sorting Receptors in the Early Secretory Pathway
Authors: Dancourt Julia , Barlowe Charles
Published: June 2010

Estimates based on proteomic analyses indicate that a third of translated proteins in eukaryotic genomes enter the secretory pathway. After folding and assembly of nascent secretory proteins in the endoplasmic reticulum (ER), the coat protein complex II (COPII) selects folded cargo for export in membrane-bound vesicles. To accommodate the great diversity in secretory cargo, protein sorting receptors are required in a number of instances for efficient ER export. These transmembrane sorting receptors couple specific secretory cargo to COPII through interactions with both cargo and coat subunits. After incorporation into COPII transport vesicles, protein sorting receptors release bound cargo in pre-Golgi or Golgi compartments, and receptors are then recycled back to the ER for additional rounds of cargo export. Distinct types of protein sorting receptors that recognize carbohydrate and/or polypeptide signals in secretory cargo have been characterized. Our current understanding of the molecular mechanisms underlying cargo receptor function are described.
Cellulosomes: Highly Efficient Nanomachines Designed to Deconstruct Plant Cell Wall Complex Carbohydrates
Authors: Fontes Carlos M.G.A. , Gilbert Harry J.
Published: June 2010

Cellulosomes can be described as one of nature's most elaborate and highly efficient nanomachines. These cell bound multienzyme complexes orchestrate the deconstruction of cellulose and hemicellulose, two of the most abundant polymers on Earth, and thus play a major role in carbon turnover. Integration of cellulosomal components occurs via highly ordered protein:protein interactions between cohesins and dockerins, whose specificity allows the incorporation of cellulases and hemicellulases onto a molecular scaffold. Cellulosome assembly promotes the exploitation of enzyme synergism because of spatial proximity and enzyme-substrate targeting. Recent structural and functional studies have revealed how cohesin-dockerin interactions mediate both cellulosome assembly and cell-surface attachment, while retaining the spatial flexibility required to optimize the catalytic synergy within the enzyme complex. These emerging advances in our knowledge of cellulosome function are reviewed here.
FRP inhibits ox-LDL-induced endothelial cell apoptosis through an Akt-NF-κB-Bcl-2 pathway and inhibits endothelial cell apoptosis in an apoE-knockout mouse model
Authors: Liu Shu , Shen Hua , Xu Ming , Liu Ou , Zhao Limin , Liu Sa , Guo Zhenheng , Du Jie
Published: June 2010

Atherosclerosis is the most common cause of cardiovascular diseases in the world. Although the development of atherosclerosis appears to be the result of multiple maladaptive pathways, a particularly important factor in the pathogenesis of atherosclerosis is oxidized low-density lipoprotein (ox-LDL), which contributes to endothelial damage. Data from our laboratory and others show that follistatin-related protein (FRP), which is expressed in the vasculature, has cardioprotective effects, suggesting that loss of FRP protection might play a role in the development of atherosclerosis. In the present study, we determined whether FRP overexpression protects against endothelial cell (EC) damage, an intermediate end point for atherosclerosis. We bred apoE-knockout (apoE−/−) mice that were FRP+ transgenic (they overexpressed FRP). We compared them with control mice (their littermates). Human umbilical vein endothelial cells (HUVECs) were isolated and treated with ox-LDL and recombinant FRP. FRP-induced signal transduction and Bcl-2 mRNA and protein stability were analyzed. After 16 wk, apoE−/− FRP+ mice had significantly fewer apoptotic ECs than controls. In vitro experiments showed that the effect of FRP on EC apoptosis was mediated by upregulation of expression of the antiapoptotic protein Bcl-2. In HUVECs, FRP upregulated Bcl-2 transcription via a PI3K-Akt-NF-κB pathway. We conclude that FRP overexpression maintains EC viability by preventing apoptosis via Bcl-2 upregulation. FRP may be a novel therapeutic target for the prevention and treatment of vascular EC injury and of atherosclerosis.
FATP2 is a hepatic fatty acid transporter and peroxisomal very long-chain acyl-CoA synthetase
Authors: Falcon Alaric , Doege Holger , Fluitt Amy , Tsang Bernice , Watson Nicki , Kay Mark A. , Stahl Andreas
Published: June 2010

Fatty acid transport protein (FATP)2, a member of the FATP family of fatty acid uptake mediators, has independently been identified as a hepatic peroxisomal very long-chain acyl-CoA synthetase (VLACS). Here we address whether FATP2 is 1) a peroxisomal enzyme, 2) a plasma membrane-associated long-chain fatty acid (LCFA) transporter, or 3) a multifunctional protein. We found that, in mouse livers, only a minor fraction of FATP2 localizes to peroxisomes, where it contributes to approximately half of the peroxisomal VLACS activity. However, total hepatic (V)LACS activity was not significantly affected by loss of FATP2, while LCFA uptake was reduced by 40%, indicating a more prominent role in hepatic LCFA uptake. This suggests FATP2 as a potential target for a therapeutic intervention of hepatosteatosis. Adeno-associated virus 8-based short hairpin RNA expression vectors were used to achieve liver-specific FATP2 knockdown, which significantly reduced hepatosteatosis in the face of continued high-fat feeding, concomitant with improvements in liver physiology, fasting glucose, and insulin levels. Based on our findings, we propose a model in which FATP2 is a multifunctional protein that shows subcellular localization-dependent activity and is a major contributor to peroxisomal (V)LACS activity and hepatic fatty acid uptake, suggesting FATP2 as a potential novel target for the treatment of nonalcoholic fatty liver disease.
The metabolic coregulator RIP140: an update
Authors: Fritah Asmaà , Christian Mark , Parker Malcolm G.
Published: June 2010

RIP140 is a transcriptional coregulator highly expressed in metabolic tissues where it has important and diverse actions. RIP140-null mice show that it plays a crucial role in the control of lipid metabolism in adipose tissue, skeletal muscle, and the liver and is essential for female fertility. RIP140 has been shown to act as a ligand-dependent transcriptional corepressor for metabolic nuclear receptors such as estrogen-related receptors and peroxisome proliferator-activated receptors. The role of RIP140 as a corepressor has been strengthened by the characterization of RIP140-overexpressing mice, although it emerges through several studies that RIP140 can also behave as a coactivator. Nuclear localization of RIP140 is important for controlling transcription of target genes and is subject to regulation by posttranslational modifications. However, cytoplasmic RIP140 has been shown to play a role in the control of metabolism through direct regulation of glucose transport in adipocytes. In this review, we focus on recent advances highlighting the growing importance of RIP140 as a regulator of energy homeostasis.
On the Relationship between Pollen Size and Genome Size
Authors: Knight Charles A. , Clancy Rachel B. , Götzenberger Lars , Dann Leighton , Beaulieu Jeremy M.
Published: June 2010

Here we test whether genome size is a predictor of pollen size. If it were, inferences of ancient genome size would be possible using the abundant paleo-palynolgical record. We performed regression analyses across 464 species of pollen width and genome size. We found a significant positive trend. However, regression analysis using phylogentically independent contrasts did not support the correlated evolution of these traits. Instead, a large split between angiosperms and gymnosperms for both pollen width and genome size was revealed. Sister taxa were not more likely to show a positive contrast when compared to deeper nodes. However, significantly more congeneric species had a positive trend than expected by chance. These results may reflect the strong selection pressure for pollen to be small. Also, because pollen grains are not metabolically active when measured, their biology is different than other cells which have been shown to be strongly related to genome size, such as guard cells. Our findings contrast with previously published research. It was our hope that pollen size could be used as a proxy for inferring the genome size of ancient species. However, our results suggest pollen is not a good candidate for such endeavors.
Correlating Phosphatidylinositol 3-Kinase Inhibitor Efficacy with Signaling Pathway Status: In silico and Biological Evaluations
Authors: Dan Shingo , Okamura Mutsumi , Seki Mariko , Yamazaki Kanami , Sugita Hironobu , Okui Michiyo , Mukai Yumiko , Nishimura Hiroyuki , Asaka Reimi , Nomura Kimie , Ishikawa Yuichi , Yamori Takao
Published: June 2010

The phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in human cancers, and several agents targeting this pathway including PI3K/Akt/mammalian target of rapamycin inhibitors have recently entered clinical trials. One question is whether the efficacy of a PI3K pathway inhibitor can be predicted based on the activation status of pathway members. In this study, we examined the mutation, expression, and phosphorylation status of PI3K and Ras pathway members in a panel of 39 pharmacologically well-characterized human cancer cell lines (JFCR39). Additionally, we evaluated the in vitro efficacy of 25 PI3K pathway inhibitors in addition to conventional anticancer drugs, combining these data to construct an integrated database of pathway activation status and drug efficacies (JFCR39-DB). In silico analysis of JFCR39-DB enabled us to evaluate correlations between the status of pathway members and the efficacy of PI3K inhibitors. For example, phospho-Akt and KRAS/BRAF mutations prominently correlated with the efficacy and the inefficacy of PI3K inhibitors, respectively, whereas PIK3CA mutation and PTEN loss did not. These correlations were confirmed in human tumor xenografts in vivo, consistent with their ability to serve as predictive biomarkers. Our findings show that JFCR39-DB is a useful tool to identify predictive biomarkers and to study the molecular pharmacology of the PI3K pathway in cancer. Cancer Res; 70(12); 4982–94. ©2010 AACR.
Frequent Attenuation of the WWOX Tumor Suppressor in Osteosarcoma Is Associated with Increased Tumorigenicity and Aberrant RUNX2 Expression
Authors: Kurek Kyle C. , Del Mare Sara , Salah Zaidoun , Abdeen Suhaib , Sadiq Hussain , Lee Suk-hee , Gaudio Eugenio , Zanesi Nicola , Jones Kevin B. , DeYoung Barry , Amir Gail , Gebhardt Mark , Warman Matthew , Stein Gary S. , Stein Janet L. , Lian Jane B. , Aqeilan Rami I.
Published: June 2010

The WW domain-containing oxidoreductase (WWOX) is a tumor suppressor that is deleted or attenuated in most human tumors. Wwox-deficient mice develop osteosarcoma (OS), an aggressive bone tumor with poor prognosis that often metastasizes to lung. On the basis of these observations, we examined the status of WWOX in human OS specimens and cell lines. In human OS clinical samples, WWOX expression was absent or reduced in 58% of tumors examined (P < 0.0001). Compared with the primary tumors, WWOX levels frequently increased in tumors resected following chemotherapy. In contrast, tumor metastases to lung often exhibited reduced WWOX levels relative to the primary tumor. In human OS cell lines having reduced WWOX expression, ectopic expression of WWOX inhibited proliferation and attenuated invasion in vitro, and suppressed tumorigenicity in nude mice. Expression of WWOX was associated with reduced RUNX2 expression in OS cell lines, whereas RUNX2 levels were elevated in femurs of Wwox-deficient mice. Furthermore, WWOX reconstitution in HOS cells was associated with downregulation of RUNX2 levels and RUNX2 target genes, consistent with the ability of WWOX to suppress RUNX2 transactivation activity. In clinical samples, RUNX2 was expressed in the majority of primary tumors and undetectable in most tumors resected following chemotherapy, whereas most metastases were RUNX2 positive. Our results deepen the evidence of a tumor suppressor role for WWOX in OS, furthering its prognostic and therapeutic significance in this disease. Cancer Res; 70(13); 5577–86. ©2010 AACR.
Concurrent Suppression of Integrin α5, Radixin, and RhoA Phenocopies the Effects of miR-31 on Metastasis
Authors: Valastyan Scott , Chang Amelia , Benaich Nathan , Reinhardt Ferenc , Weinberg Robert A.
Published: June 2010

miR-31 inhibits breast cancer metastasis via the pleiotropic suppression of a cohort of prometastatic target genes that include integrin α5 (ITGA5), radixin (RDX), and RhoA. We previously showed that the concomitant overexpression of ITGA5, RDX, and RhoA was capable of overriding the antimetastatic effects of ectopically expressed miR-31 in vivo. However, these prior studies failed to investigate whether the combined suppression of the endogenous mRNAs encoding these three proteins recapitulated the in vivo consequences of miR-31 expression on metastasis. We show here that short hairpin RNA–mediated concurrent downregulation of ITGA5, RDX, and RhoA is sufficient to phenocopy the full spectrum of described influences of miR-31 on metastasis in vivo, including the effects of this microRNA (miRNA) on local invasion, early post-intravasation events, and metastatic colonization. These findings provide mechanistic insights into the metastatic process and have implications about the importance of pleiotropy for the biological actions of miRNAs. Cancer Res; 70(12); 5147–54. ©2010 AACR.
Overexpression of p73 as a Tissue Marker for High-Risk Gastritis
Authors: Carrasco Gonzalo , Diaz Jose , Valbuena Jose R. , Ibanez Paulina , Rodriguez Paz , Araya Gabriela , Rodriguez Carolina , Torres Javiera , Duarte Ignacio , Aravena Edmundo , Mena Fernando , Barrientos Carlos , Corvalan Alejandro H.
Published: June 2010

Purpose: Histologic assessment of high-risk gastritis for the development of gastric cancer is not well defined. The identification of tissue markers together with the integration of histologic features will be required for this assessment.

Experimental Design: Matched tumor/nontumor adjacent mucosa (NTAM) of 91 early gastric cancer and 148 chronic gastritis cases were evaluated for histologic characteristics (atrophy, intestinal metaplasia, chronic inflammation, polymorphonuclear infiltration, and Helicobacter pylori) by the Sydney System. Atrophy risk assessment was also evaluated by the Operative Link on Gastritis Assessment (OLGA) staging system. Eight tissue markers (BRCA1, HSP90, STAT1, FHIT, EGFR, p73, p53, p16INK4a) and EBV were also evaluated by tissue microarray/immunohistochemistry/in situ hybridization platform. Data were analyzed by contingency tables (2 × 2) using Fisher's exact two-tailed test (P < 0.001) and integrated by Significance Analysis of Microarrays (SAM) and clustering analysis.

Results: Histologically, NTAM have severe intestinal metaplasia/chronic inflammation and severe atrophy assessed by Sydney and OLGA staging systems. H. pylori infection was similar in both groups, and EBV was found only in 5.5% of the tumor samples. Overexpression of p73 was higher in NTAM (50.5%) than in chronic gastritis (10.8%; P < 0.0001). Integration of histologic features and tissue markers showed that overexpression of p73, severe atrophy, and OLGA stage 4 were the most relevant features in NTAM. Clustering analysis correctly assigned NTAM and control cases (P < 0.0001).

Conclusions: Overexpression of p73 should be considered for the assessment of high-risk chronic gastritis. SAM allows the integration of histology and tissue markers for this assessment. Clin Cancer Res; 16(12); 3253–9. ©2010 AACR.
Controversies in Cancer Stem Cells: Targeting Embryonic Signaling Pathways
Authors: Takebe Naoko , Ivy S. Percy
Published: June 2010

Selectively targeting cancer stem cells (CSC) or tumor-initiating cells (TIC; from this point onward referred to as CSCs) with novel agents is a rapidly emerging field of oncology. Our knowledge of CSCs and their niche microenvironments remains a nascent field. CSC's critical dependence upon self-renewal makes these regulatory signaling pathways ripe for the development of experimental therapeutic agents. Investigational agents targeting the Notch, Hedgehog, and Wnt pathways are currently in late preclinical development stages, with some early phase 1-2 testing in human subjects. This series of articles will provide an overview and summary of the current state of knowledge of CSCs, their interactive microenvironment, and how they may serve as important targets for antitumor therapies. We also examine the scope and stage of development of early experimental agents that specifically target these highly conserved embryonic signaling pathways. Clin Cancer Res; 16(12); 3106–12. ©2010 AACR.
Phase II Clinical and Pharmacokinetic Study of Plitidepsin 3-Hour Infusion Every Two Weeks Alone or with Dexamethasone in Relapsed and Refractory Multiple Myeloma
Authors: Mateos María Victoria , Cibeira Maria Teresa , Richardson Paul G. , Prosper Felipe , Oriol Albert , de la Rubia Javier , Lahuerta Juan José , García-Sanz Ramón , Extremera Sonia , Szyldergemajn Sergio , Corrado Claudia , Singer Harald , Mitsiades Constantine S. , Anderson Kenneth C. , Bladé Joan , San Miguel Jesús
Published: June 2010

Purpose: This trial evaluated the antitumor activity and safety of the marine-derived cyclodepsipeptide plitidepsin in patients with relapsed/refractory multiple myeloma.

Experimental Design: This was a prospective, multicenter, open-label, single-arm, phase II trial with plitidepsin at 5 mg/m2 as a 3-hour i.v. infusion every two weeks. The protocol was amended to allow patients with suboptimal response to single-agent plitidepsin to add 20 mg/day on days 1 to 4 of oral dexamethasone every two weeks.

Results: Fifty-one patients started treatment with plitidepsin and 47 were evaluable for efficacy. The overall response rate (complete response plus partial response plus minimal response) was 13% with plitidepsin alone and 22% in the cohort of patients with the addition of dexamethasone (n = 19, 18 evaluable). Both plitidepsin alone and with dexamethasone were feasible and well tolerated. Anemia (29%) and thrombocytopenia (18%) were the most frequent grade 3/4 hematologic toxicities. Fatigue (16%), muscular toxicity (6%), and transient alanine aminotransferase/aspartate aminotransferase (27%) and creatine phosphokinase (23%) increases were the most relevant nonhematologic side effects. A prolonged plasma half-life was observed in responding patients as compared with nonresponding patients (P = 0.009).

Conclusions: Single-agent plitidepsin has limited but reproducible activity in relapsed/refractory multiple myeloma patients. Activity observed after dexamethasone addition merits further study. Both regimens were well tolerated in this heavily pretreated population. Clin Cancer Res; 16(12); 3260–9. ©2010 AACR.
Brain Allometry and Neural Plasticity in the Bumblebee Bombus occidentalis
Authors: Riveros Andre J. , Gronenberg Wulfila
Published: June 2010

Brain plasticity is a common phenomenon across animals and in many cases it is associated with behavioral transitions. In social insects, such as bees, wasps and ants, plasticity in a particular brain compartment involved in multisensory integration (the mushroom body) has been associated with transitions between tasks differing in cognitive demands. However, in most of these cases, transitions between tasks are age-related, requiring the experimental manipulation of the age structure in the studied colonies to distinguish age and experience-dependent effects. To better understand the interplay between brain plasticity and behavioral performance it would therefore be advantageous to study species whose division of labor is not age-dependent. Here, we focus on brain plasticity in the bumblebee Bombus occidentalis, in which division of labor is strongly affected by the individual’s body size instead of age. We show that, like in vertebrates, body size strongly correlates with brain size. We also show that foraging experience, but not age, significantly correlates with the increase in the size of the mushroom body, and in particular one of its components, the medial calyx. Our results support previous findings from other social insects suggesting that the mushroom body plays a key role in experience-based decision making. We also discuss the use of bumblebees as models to analyze neural plasticity and the association between brain size and behavioral performance.
Allometric Scaling of the Tectofugal Pathway in Birds
Authors: Iwaniuk Andrew N. , Gutierrez-Ibanez Cristian , Pakan Janelle M.P. , Wylie Douglas R.
Published: June 2010

Recent studies have shown that the relative sizes of visual regions in the avian brain are correlated with behavioral differences among species. Despite the fact that the tectofugal pathway is the primary source of visual input to the avian brain, detailed interspecific comparisons of the relative size of nuclei within the pathway, the optic tectum, nucleus rotundus and entopallium, are wanting. Here, we examine the allometric scaling relationships of each of these brain regions relative to the brain as a whole using conventional and phylogenetically based statistics across 113 species. Our results show that the relative size of tectofugal regions of the avian brain varies significantly among avian orders. More specifically, waterfowl (Anseriformes), parrots (Psittaciformes) and owls (Strigiformes) have significantly smaller tectofugal brain regions than other birds. At the opposite end of the spectrum, we found little evidence for the significant enlargement of any tectofugal region among the orders that we sampled. The lack of such hypertrophy likely reflects the heterogeneous organization of the optic tectum, nucleus rotundus and entopallium. We therefore speculate that if neural adaptations do exist in the avian tectofugal pathway that are correlated with behavior, they occur at a more refined level than simple volumetrics.
Statin Use and Risk of Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders
Authors: Sørensen Henrik Toft , Riis Anders Hammerich , Lash Timothy L. , Pedersen Lars
Published: June 2010

Background—

Use of statins has been associated with an amyotrophic lateral sclerosis-like syndrome in 2 analyses of overlapping surveillance databases that record adverse events potentially related to prescription drug use. We assessed whether statin use is associated with the occurrence of amyotrophic lateral sclerosis and other motor neuron disorders.

Methods and Results—

We conducted a population-based case-control study in Northern Denmark, with a population of 1.8 million. From the Danish National Registry of Patients, we identified incident cases coded with amyotrophic lateral sclerosis or other motor neuron syndromes during the period from 1999 to 2008. We selected 10 population control subjects matched to cases on sex, birth year, and calendar time. Statin use was ascertained in the prescription database in the region—and so recorded before diagnosis—and associated with disease occurrence by conditional logistic regression adjusting for covariates. We identified 556 cases of amyotrophic lateral sclerosis or other motor neuron syndromes and 5560 population control subjects. The odds ratio associating disease occurrence with statin use was 0.96 (95% confidence interval, 0.73 to 1.28). Recent users of statins, former users, and users of short or long duration had similarly near-null associations.

Conclusions—

Any risk of amyotrophic lateral sclerosis associated with statin use probably is small, so outweighed by the important clinical advantages of statin medications to prevent and treat cardiovascular diseases.
In Defense of the City and the Polity: The Xuanmiao Monastery and the Qing Anti-Taiping Campaigns in Mid-Nineteenth Century Nanyang
Authors: Liu Xun
Published: June 2010

This paper examines the role played by the Quanzhen Daoist Xuanmiao monastery in the defense of Nanyang (Henan) during the Taiping rebellion. It shows that Daoist loyalty to the Qing state and to the local community did not just stem from the abbot's personal hatred of the Taiping; it also mirrored the monastery's established pattern of collaboration with the imperial state since the early Qing and its long history of ritual service to and economic involvement in the local community. Because of its wealth and cultural and political influence the Xuanmiao monastery functioned as a vital and dynamic actor in shaping the history and society of late nineteenth-century Nanyang. Cet article est consacré au rôle joué par un monastère taoïste Quanzhen, le Xuanmiao guan, dans la défense de Nanyang (Henan) pendant la rébellion des Taiping. Il montre que la loyauté des taoïstes envers l'État Qing et la communauté locale n'était pas simplement l'effet de la détestation qu'inspiraient les Taiping au supérieur du monastère; elle reflétait aussi un modèle bien établi de collaboration avec l'État impérial depuis le début des Qing, ainsi qu'une longue histoire de service rituel et d'intervention économique au bénéfice de la communauté. Grâce à sa richesse et à son influence politique et culturelle, le monastère Xuanmiao a été un acteur important et dynamique dans l'histoire et l'évolution sociale de Nanyang à la fin du xixe siècle.
The Impact of Gentrification on Ethnic Neighbourhoods in Toronto: A Case Study of Little Portugal
Authors: Murdie Robert , Teixeira Carlos
Published: June 2010

Despite extensive literature on the nature and impact of gentrification, there has been little consideration of the effects of gentrification on ethnic neighbourhoods. This study evaluates the negative and positive effects of gentrification on the Portuguese in west central Toronto. Details concerning the settlement patterns of the Portuguese, the characteristics of Portuguese residents and patterns of gentrification in inner-city Toronto were obtained from census data. Evaluations of neighbourhood change and attitudes of the residents towards gentrification were obtained from key informant and focus group interviews. The results suggest considerable ambivalence among the respondents, but most agreed that the long-term viability of Little Portugal as an immigrant reception area with a good supply of low-cost housing is in doubt.
Institutions in Theories of Land Markets: Illustrated by the Dutch Market for Agricultural Land
Authors: Needham Barrie , Segeren Arno , Buitelaar Edwin
Published: June 2010

Theories of land markets should be intellectually sound and should be able to explain and predict market outcomes, such as price and volume of transactions, changes in these and locations of different land uses. Theories based on neo-classical economics, which largely ignore the role of institutions, are not intellectually sound because it is known that markets cannot work without institutions. Nor do these theories predict outcomes satisfactorily. Moreover, they assume market mechanisms and do not investigate them critically. This paper explores how institutions may be taken into account in theories of land markets and whether that leads to better theories both of market outcomes and of market processes. New institutional economics provides the tools to investigate how the interactions between market actors are influenced by institutions. And the ‘old’ institutional economics emphasises how institutions influence the motivations and preferences of those actors. The conclusion is that there cannot be a general theory of land markets, only theories with a limited applicability and scope. Such theories can be used to explain the effects of small changes and to predict the effects of marginal changes in institutions. In that latter use, these theories can be used for designing land policy. How institutions can be incorporated into theory is illustrated by analysing the Dutch market for agricultural land. This shows how institutions affect the outcomes in that market and the consequences for the transformation of land from agriculture to urban use.
Do Numerical Rating Scales and the Roland-Morris Disability Questionnaire capture changes that are meaningful to patients with persistent back pain?
Authors: Hush Julia M , Refshauge Kathryn M , Sullivan Gerard , De Souza Lorraine , McAuley James H
Published: June 2010

Objectives: To investigate patients’ views about two common outcome measures used for back pain: Numerical Rating Scales for pain and the Roland-Morris Disability Questionnaire.

Subjects: Thirty-six working adults who had previously sought primary care for back pain and who could speak and read English.

Method: Eight focus groups were conducted to explore participants’ views about the 11-point Numerical Rating Scales and the 24-item Roland-Morris Disability Questionnaire. Each group was led by a facilitator and an interview topic guide was used. Audio recordings of focus groups were transcribed verbatim. Framework analysis was used to chart participants’ views and an interpretive analysis performed to explain the findings.

Results: Participants reported that neither the Roland-Morris nor the Numerical Rating Scales captured the complex personal experience of pain or relevant changes in their condition. The time-frame of assessment was identified as particularly problematic and the Roland-Morris did not capture relevant functional domains.

Conclusion: This study provides empirical data that working adults with persistent back pain consider these clinical outcome measures largely inadequate. These measures currently used for back pain may contribute to misleading conclusions about treatment efficacy and patient recovery.
Teaching action sequences after brain injury: a comparison of modelling and moulding techniques
Authors: Zlotowitz Sally , Fallow Kirsty , Illingworth Victoria , Liu Clarence , Greenwood Richard , Papps Ben
Published: June 2010

Objective: To compare the relative effectiveness of a modelling and a moulding instructional technique for teaching action sequences to participants with brain injury in rehabilitation settings.

Design: Randomized crossover design.

Setting: Regional Neurological Rehabilitation Unit.

Subjects: Sixteen participants with an acquired brain injury undergoing early inpatient rehabilitation.

Intervention: Participants were instructed to recall two different sequences of seven hand movements after a short (5 minutes) and longer delay (30 minutes). Participants were taught the sequences using moulding and modelling techniques.

Main outcome measure: Participants’ recall of the sequence measured after the short and longer delay for each instructional technique.

Results: Participants recalled the sequence after the longer delay (30 minutes) significantly more accurately (Z = 1.91, P =0.028) when taught using the modelling instructional technique (mean 2.63, SD 1.55) compared to the moulding technique (mean 1.56, SD 1.63). There were no significant differences between the participants’ recall scores after a short delay. Participants who scored lower on a delayed memory subtest of a neuropsychological test benefitted more from the modelling technique.

Conclusion: The use of a modelling instructional technique to teach brain-injured participants an action sequence during their rehabilitation may be more effective for their longer term performance than a moulding instructional technique.
Prodynorphin gene deletion increased anxiety-like behaviours, impaired the anxiolytic effect of bromazepam and altered GABAA receptor subunits gene expression in the amygdala
Authors: Femenía Teresa , Pérez-Rial Sandra , Urigüen Leyre , Manzanares Jorge
Published: June 2010

This study evaluated the role of prodynorphin gene in the regulation of anxiety and associated molecular mechanisms. Emotional responses were assessed using the light–dark test, elevated plus maze and social interaction tests in prodynorphin knockout and wild-type mice. Corticotrophin releasing factor and proopiomelanocortin gene expressions in the hypothalamus were evaluated after restraint stress using in situ hybridization. The anxiolytic efficacy of bromazepam and GABAA receptor subunits gene expression in the amygdala were also assessed in both genotypes. The deletion of prodynorphin increased anxiety-like behaviours and proopiomelanocortin gene expression in the arcuate nucleus (two-fold). Moreover, the anxiolytic action of bromazepam was significantly attenuated in the mutant mice. Decreased GABAAγ2 and increased GABAAβ2 gene expression receptor subunits were found in the amygdala of prodynorphin knockout mice. These results indicate that deletion of prodynorphin gene is associated with increased anxiety-like behaviours, enhanced sensibility response to stress stimuli, reduced anxiolytic efficacy of bromazepam and altered expression of the GABAA receptor subunits.