bluuebunny/crossref_metadata_2025_split huggingface dataset:
Creutzfeldt–Jacob disease mimics, or how to sort out the subacute encephalopathy patient
Authors: Murray Katherine 
Published: April 2011

ABSTRACT
Sporadic Creutzfeldt–Jacob disease (CJD) is a rare untreatable neurodegenerative disease which every neurologist will occasionally encounter during their career. However, it is likely to appear on their differential diagnosis list significantly more frequently. Numerous conditions can present with subacute encephalopathy which might be sporadic CJD and this article explores these diagnoses. It includes the commonest sporadic CJD mimics which are neurodegenerative, and highlights the relatively rare treatable mimics which must not be missed. It discusses relevant investigations, including serum antibodies, CSF, electroencephalography and MR brain imaging, and strategies when preliminary investigations fail to support sporadic CJD but no alternative diagnosis is readily apparent.
Chemical modifications of Bacillus subtilis tryptophanyl-tRNA synthetase
Authors: Xue Hong , Xue Yilong , Doublié Sylvie , Carter, Jr. Charles W 
Published: April 2011

A concerted conformational change in Bacillus subtilis tryptophanyl-tRNA synthetase (TrpRS) was evident from previous fluorescence on the quenching of the single Trp residue Trp-92 in the 4FTrp-AMP complexed enzyme. In this study, chemical modifications of the B. subtilis TrpRS were employed to further characterize this conformational change, with the single Trp residue serving as a marker for monitoring the change. Modifications of the enzyme by means of the Trp-specific agent N-bromosuccinimide (NBS) or 3-bromo-3-methyl-2-(2-nitrophenylmercapto)-3H-indole (BNPS-skatole) inactivated the enzyme in accord with the essential role of Trp-92, as identified previously by site-directed mutagenesis. ATP sensitized TrpRS toward inactivation by NBS and BNPS-skatole, which suggested a conformational change that resulted in greater accessibility of Trp-92 toward modifications. In contrast, the cognate tRNATrp substrate exerted a specific protective effect against inactivation by both of the reagents, indicating that the TrpRS-tRNATrp interaction reduces the accessibility of Trp-92 under our experimental conditions. By comparison, modification of sulfhydryl groups by means of iodoacetamide did not reduce TrpRS activity. Observations on Trp-specific modification and substrate protection effects are discussed in the context of the Bacillus stearothermophilus TrpRS crystal structure. Key words: aminoacyl-tRNA synthetase, Bacillus subtilis, chemical modification, conformational change, transfer RNA, tryptophanyl-tRNA synthetase.
Characterization of stable RNAs from the resected intestinal tissues of individuals with either Crohn's disease or ulcerative colitis
Authors: Roy Guylaine , Mercure Stéphane , Beuvon Frédéric , Perreault Jean-Pierre 
Published: April 2011

Circular RNAs reminiscent of viroids and the human hepatitis delta virus have been proposed as possible nonconventional pathogens responsible for Crohn's disease and ulcerative colitis, two inflammatory bowel diseases. Consequently, RNA was extracted from various areas of intestinal tissues from individuals with either Crohn's disease or ulcerative colitis as well as several appropriate control diseases, and analyzed by two-dimensional gel electrophoresis. No circular viroid-like RNAs (<1500 nucleotides) were detected, confirming a previous report that was limited to the investigation of small RNAs (<300 nucleotides). However, three small, unusually stable, linear RNAs were shown to be associated to both Crohn's disease and ulcerative colitis tissues: a specific 28S ribosomal RNA cleavage product characterized previously; a 5.8S ribosomal RNA conformer; and a fragment homologous to transcripts from DNA CpG islands. The two last RNAs were detected prior to visible morphological tissue alterations, suggesting that they are produced early during the inflammation and that they have value as molecular diagnostic tools for the inflammatory bowel diseases. The potential cellular mechanisms producing these RNAs and their involvement in inflammatory bowel disease are discussed. Key words: ribosomal RNA, inflammatory bowel diseases, human intestine, inflammation, viroids.
The brain in evolution and involution
Authors: Parent André 
Published: April 2011

This paper provides an overview of the phylogenetic evolution and structural organization of the basal ganglia. These large subcortical structures that form the core of the cerebral hemispheres directly participate in the control of psychomotor behavior. Neuroanatomical methods combined with transmitter localization procedures were used to study the chemical organization of the forebrain in each major group of vertebrates. The various components of the basal ganglia appear well developed in amniote vertebrates, but remain rudimentary in anamniote vertebrates. For example, a typical substantia nigra composed of numerous dopaminergic neurons that project to the striatum already exists in the brain of reptiles. Other studies in mammals show that glutamatergic cortical inputs establish distinct functional territories within the basal ganglia, and that neurons in each of these territories act upon other brain neuronal systems principally via a GABAergic disinhibitory output mechanism. The functional status of the various basal ganglia chemospecific systems was examined in animal models of neurodegenerative diseases, as well as in postmortem material from Parkinson's and Huntington's disease patients. The neurodegenerative processes at play in such conditions specifically target the most phylogenetically ancient components of the brain, including the substantia nigra and the striatum, and the marked involution of these brain structures is accompanied by severe motor and cognitive deficits. Studies of neural mechanisms involved in these akinetic and hyperkinetic disorders have led to a complete reevaluation of the current model of the functional organization of the basal ganglia in both health and disease. Key words: brain phylogeny, basal ganglia, neurotransmitters, neurodegenerative disorders.
Evidence for recent groundwater flow through Late Wisconsinan till near Toronto, Ontario
Authors: Gerber R E , Howard K WF 
Published: April 2011

The Northern till is a thick (~50 m) Late Winsconsinan diamict unit that occurs throughout south-central Ontario. The till has generally been regarded as massive and uniform, with a very low vertical hydraulic conductivity. It is similar to many other till units of mid-continental North American glaciated terrain in that it is believed to inhibit recharge to underlying aquifers and afford a high degree of protection to these aquifers from surface and near-surface sources of contamination. Standard methods of estimating hydraulic conductivity (K) for the Northern till, such as laboratory testing of core samples (other studies) and risingfalling head field piezometer tests (this study and other studies), characteristically yield values on the order of 1011 to 109 m/s. Typically, these values indicate advective traveltimes through the till on the order of hundreds to thousands of years. In contrast, isotopic evidence (2H, 18O, and 3H) from till pore waters indicates the presence of modern (post-1952) waters at depths of up to 50 m, suggesting either that certain facies of the till are considerably more permeable or that minor sand lenses or hydrogeologically active secondary permeability structures are locally important. In some areas, vertical flow velocities may approach 1 m/year. By comparing pore-water isotopic data from cores acquired using mud (sodium bentonite) and dry rotary methods, this study further demonstrates that representative pore-water samples can be obtained using a drilling fluid providing care is taken in preparing core samples for analysis. Key words: till, aquitard, permeability, recharge, contaminant transport, isotopes.
Shear strength characteristics of two saprolitic soils
Authors: Gan Julian K-M , Fredlund D G 
Published: April 2011

The saturated and unsaturated shear strength behavior of an undisturbed, completely decomposed fine ash tuff and an undisturbed, completely decomposed granite from Hong Kong were studied using direct shear and triaxial tests. The completely decomposed fine ash tuff is a fine- to medium-grained saprolite. The completely decomposed granite is a coarse-grained saprolite. Results show that matric suction increases the shear strength of both soils. The extent of the increase is the shear strength with matric suction is related to the soil-water characteristic curve for the soil and to the amount of dilation during shear. The effect of matric suction on the shear strength was more pronounced for the fine- to medium-grained completely decomposed fine ash tuff than for the coarse-grained completely decomposed granite. These studies on the saprolitic soils provide insight into the understanding of the shear strength of unsaturated, coarse-grained soils. Key words: saprolites, shear strength, matric suction, triaxial, direct shear, coarse-grained soils.
Serial Magnetic Resonance Spectroscopy Reveals a Direct Metabolic Effect of Cediranib in Glioblastoma
Authors: Kim Heisoog , Catana Ciprian , Ratai Eva-Maria , Andronesi Ovidiu C. , Jennings Dominique L. , Batchelor Tracy T. , Jain Rakesh K. , Sorensen A. Gregory 
Published: April 2011

Abstract
Proton magnetic resonance spectroscopy is increasingly used in clinical studies of brain tumor to provide information about tissue metabolic profiles. In this study, we evaluated changes in the levels of metabolites predominant in recurrent glioblastoma multiforme (rGBM) to characterize the response of rGBM to antiangiogenic therapy. We examined 31 rGBM patients treated with daily doses of cediranib, acquiring serial chemical shift imaging data at specific time points during the treatment regimen. We defined spectra from three regions of interest (ROI)—enhancing tumor (ET), peritumoral tissue, and normal tissue on the contralateral side (cNT)—in post-contrast T1-weighted images, and normalized the concentrations of N-acetylaspartate (NAA) and choline (Cho) in each ROI to the concentration of creatine in cNT (norCre). We analyzed the ratios of these normalized metabolites (i.e., NAA/Cho, NAA/norCre, and Cho/norCre) by averaging all patients and categorizing two different survival groups. Relative to pretreatment values, NAA/Cho in ET was unchanged through day 28. However, after day 28, NAA/Cho significantly increased in relation to a significant increase in NAA/norCre and a decrease in Cho/norCre; interestingly, the observed trend was reversed after day 56, consistent with the clinical course of GBM recurrence. Notably, receiver operating characteristic analysis indicated that NAA/Cho in tumor shows a high prediction to 6-month overall survival. These metabolic changes in these rGBM patients strongly suggest a direct metabolic effect of cediranib and might also reflect an antitumor response to antiangiogenic treatment during the first 2 months of treatment. Further study is needed to confirm these findings. Cancer Res; 71(11); 3745–52. ©2011 AACR.
IFN-γ Inhibits Gastric Carcinogenesis by Inducing Epithelial Cell Autophagy and T-Cell Apoptosis
Authors: Tu Shui Ping , Quante Michael , Bhagat Govind , Takaishi Shigeo , Cui Guanglin , Yang Xiang Dong , Muthuplani Sureshkumar , Shibata Wataru , Fox James G. , Pritchard D. Mark , Wang Timothy C. 
Published: April 2011

AbstractIFN-γ mediates responses to bacterial infection and autoimmune disease, but it is also an important tumor suppressor. It is upregulated in the gastric mucosa by chronic Helicobacter infection; however, whether it plays a positive or negative role in inflammation-associated gastric carcinogenesis is unexplored. To study this question, we generated an H+/K+-ATPase-IFN-γ transgenic mouse that overexpresses murine IFN-γ in the stomach mucosa. In contrast to the expected proinflammatory role during infection, we found that IFN-γ overexpression failed to induce gastritis and instead inhibited gastric carcinogenesis induced by interleukin-1beta (IL-1β) and/or Helicobacter infection. Helper T cell (Th) 1 and Th17 immune responses were inhibited by IFN-γ through Fas induction and apoptosis in CD4 T cells. IFN-γ also induced autophagy in gastric epithelial cells through increased expression of Beclin-1. Finally, in the gastric epithelium, IFN-γ also inhibited IL-1β- and Helicobacter-induced epithelial apoptosis, proliferation, and Dckl1+ cell expansion. Taken together, our results suggest that IFN-γ coordinately inhibits bacterial infection and carcinogenesis in the gastric mucosa by suppressing putative gastric progenitor cell expansion and reducing epithelial cell apoptosis via induction of an autophagic program. Cancer Res; 71(12); 4247–59. ©2011 AACR.
The Hypoxia-Associated Factor Switches Cells from HIF-1α- to HIF-2α-Dependent Signaling Promoting Stem Cell Characteristics, Aggressive Tumor Growth and Invasion
Authors: Koh Mei Yee , Lemos Robert , Liu Xiuping , Powis Garth 
Published: April 2011

Abstract
Most solid tumors and their metastases experience periods of low oxygen or hypoxia, which is of major clinical significance as it promotes both tumor progression and resistance to therapy. Critical mediators of the hypoxic response are the hypoxia-inducible factors HIF-1α and HIF-2α. The HIFs are nonredundant and regulate both overlapping and unique downstream target genes. Here, we describe a novel mechanism for the switch between HIF-1α- and HIF-2α–dependent transcription during tumor hypoxia caused by the hypoxia associated factor (HAF). HAF is overexpressed in a variety of tumors and its levels are decreased during acute hypoxia, but increased following prolonged hypoxia. We have previously identified HAF as an E3 ubiquitin ligase that binds and ubiquitinates HIF-1α by an oxygen and pVHL-independent mechanism, thus targeting HIF-1α for proteasomal degradation. Here, we show that HAF also binds to HIF-2α, but at a different site than HIF-1α, and increases HIF-2α transactivation without causing its degradation. HAF, thus, switches the hypoxic response of the cancer cell from HIF-1α–dependent to HIF-2α–dependent transcription and activates genes involved in invasion such as MMP9, PAI-1, and the stem cell factor OCT-3/4. The switch to HIF-2α–dependent gene expression caused by HAF also promotes an enriched tumor stem cell population, resulting in highly aggressive tumors in vivo. Thus, HAF, by causing a switch from a HIF-1α- to HIF-2α–dependent response to hypoxia, provides a mechanism for more aggressive growth of tumors under prolonged hypoxia. Cancer Res; 71(11); 4015–27. ©2011 AACR.
Mild Elevation of Body Temperature Reduces Tumor Interstitial Fluid Pressure and Hypoxia and Enhances Efficacy of Radiotherapy in Murine Tumor Models
Authors: Sen Arindam , Capitano Maegan L. , Spernyak Joseph A. , Schueckler John T. , Thomas Seneca , Singh Anurag K. , Evans Sharon S. , Hylander Bonnie L. , Repasky Elizabeth A. 
Published: April 2011

Abstract
Human and rodent solid tumors often exhibit elevated interstitial fluid pressure (IFP). This condition is recognized as a prognostic indicator for reduced responses to therapy and decreased disease-free survival rate. In the present study, we tested whether induction of a thermoregulatory-mediated increase in tissue blood flow, induced by exposure of mice to mild environmental heat stress, could influence IFP and other vascular parameters within tumors. Using several murine tumor models, we found that heating results in a sustained reduction in tumor IFP correlating with increased tumor vascular perfusion (measured by fluorescent imaging of perfused vessels, laser Doppler flowmetry, and MRI) as well as a sustained reduction in tumor hypoxia. Furthermore, when radiation therapy was administered 24 hours postheating, we observed a significant improvement in efficacy that may be a result of the sustained reduction in tumor hypoxia. These data suggest, for the first time, that environmental manipulation of normal vasomotor function is capable of achieving therapeutically beneficial changes in IFP and microvascular function in the tumor microenvironment. Cancer Res; 71(11); 3872–80. ©2011 AACR.
Uncoupling Cancer Mutations Reveals Critical Timing of p53 Loss in Sarcomagenesis
Authors: Young Nathan P. , Crowley Denise , Jacks Tyler 
Published: April 2011

Abstract
It is well accepted that cancer develops following the sequential accumulation of multiple alterations, but how the temporal order of events affects tumor initiation and/or progression remains largely unknown. Here, we describe a mouse model that allows for temporally distinct cancer mutations. By integrating a Flp-inducible allele of K-rasG12D with established methods for Cre-mediated p53 deletion, we were able to separately control the mutation of these commonly associated cancer genes in vitro and in vivo. We show that delaying p53 deletion relative to K-rasG12D activation reduced tumor burden in a mouse model of soft-tissue sarcoma, suggesting that p53 strongly inhibits very early steps of transformation in the muscle. Furthermore, using in vivo RNA interference, we implicate the p53 target gene p21 as a critical mediator in this process, highlighting cell-cycle arrest as an extremely potent tumor suppressor mechanism. Cancer Res; 71(11); 4040–7. ©2011 AACR.
The Death of the Cancer Cell
Authors: Sonnenschein Carlos , Soto Ana M. 
Published: April 2011

AbstractFor a century, the perception that there are qualitative differences between a normal cell and a cell belonging to a tumor has dominated discussions aimed at explaining cancer. However, an analysis of the experimental evidence suggests that individual normal cells and individual cancer cells share the same two fundamental behavioral properties, namely, proliferation and motility. Each individual cancer cell carries no recognizable molecules or structures that make them consistently distinguishable from normal cells. Herein, we argue that the differences between normal and cancerous states are instead identifiable at the tissue level of biological organization, and therefore, the search for identification of a cancer cell should be abandoned. Cancer Res; 71(13); 4334–7. ©2011 AACR.
Silencing Survivin Splice Variant 2B Leads to Antitumor Activity in Taxane-Resistant Ovarian Cancer
Authors: Vivas-Mejia Pablo E. , Rodriguez-Aguayo Cristian , Han Hee-Dong , Shahzad Mian M.K. , Valiyeva Fatma , Shibayama Mineko , Chavez-Reyes Arturo , Sood Anil K. , Lopez-Berestein Gabriel 
Published: April 2011

Abstract
Purpose: To study the role of survivin and its splice variants in taxane-resistant ovarian cancer.
Experimental Design: We assessed the mRNA levels of survivin splice variants in ovarian cancer cell lines and ovarian tumor samples. siRNAs targeting survivin were designed to silence all survivin splice variants (T-siRNA) or survivin 2B (2B-siRNA) in vitro and orthotopic murine models of ovarian cancer. The mechanism of cell death was studied in taxane-resistant ovarian cancer cells and in tumor sections obtained from different mouse tumors.
Results: Taxane-resistant ovarian cancer cells express higher survivin mRNA levels than their taxane-sensitive counterparts. Survivin 2B expression was significantly higher in taxane-resistant compared with -sensitive cells. Silencing survivin 2B induced growth inhibitory effects similar to silencing total survivin in vitro. In addition, survivin 2B-siRNA incorporated into DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) nanoliposomes resulted in significant reduction in tumor growth (P &lt; 0.05) in orthotopic murine models of ovarian cancer, and these effects were similar to T-siRNA-DOPC. The antitumor effects were further enhanced in combination with docetaxel chemotherapy (P &lt; 0.01). Finally, we found a significant association between survivin 2B expression and progression-free survival in 117 epithelial ovarian cancers obtained at primary debulking surgery.
Conclusions: These data identify survivin 2B as an important target in ovarian cancer and provide a translational path forward for developing new therapies against this target. Clin Cancer Res; 17(11); 3716–26. ©2011 AACR.
Differences in Base of Articulation for Consonants among Catalan Dialects
Authors: Recasens Daniel 
Published: April 2011

Abstract
Electropalatographic data for several front lingual consonants, i.e., the dental /t/, the alveolars /n, l, s, r/ and the alveolopalatals /t.,∫ ∫, λ, η/, show differences in constriction anteriority among Catalan dialects varying in the progression Valencian > Eastern, with the Majorcan dialect occupying an intermediate position. These differences do not conform to speaker- dependent differences in palate morphology and, to the extent that they operate on a varied range of consonants, may be attributed to base of articulation. Deviations from this pattern are associated with manner of articulation and symmetry demands. A specific dialect- dependent relationship between tongue dorsum contact and constriction fronting is interpreted assuming the existence of less laminal, more apical dental and alveolar stops, and less dorsal, more laminal alveolopalatals, in Valencian than in the other two dialects. These data are interpreted in terms of the articulatory characteristics for different tongue front settings which have been proposed in the literature.
Von Willebrand Factor and ADAMTS13
Authors: Stepanian Alain , Cohen-Moatti Marie , Sanglier Thibaut , Legendre Paulette , Ameziane Nejma , Tsatsaris Vassilis , Mandelbrot Laurent , de Prost Dominique , Veyradier Agnès 
Published: April 2011

Objective—
The goal of this study was to search for an association between a desintegrin-like and metalloprotease thrombospondin type 1 motif, member 13 (ADAMTS13) levels and the occurrence of preeclampsia, its characteristics (time-onset and severity), and its consequences (occurrence of fetal growth restriction or preterm delivery).

Methods and Results—
We studied 140 pairs of women in a case-control study with 3 matching criteria: maternal age, gestational age, and ethnic origin. We measured ADAMTS13 activity using a fluorescence resonance energy transfer assay with the fluorescence resonance energy transfer-VWF73 peptide. ELISA was used to assess protein antigen levels: ADAMTS13, von Willebrand Factor (VWF), interleukin-6, C-reactive protein, P-selectin, and thrombospondin-1. The lowest levels of ADAMTS13 (activity ≤70% or antigen ≤592 ng/mL) were significantly associated with preeclampsia (odds ratios [OR] [95% confidence interval] of 4.2 [1.1 to 15] and 14.3 [1.7 to 123], respectively). This association was independent of VWF levels and preeclampsia risk factors but dependent on interleukin-6 and C-reactive protein levels for ADAMTS13 activity. Levels of ADAMTS13 activity (≤57%) were significantly associated with early-onset preeclampsia (OR=2.5 [1.1 to 5.8]). Severe preeclampsia was associated with the highest levels of P-selectin (>57 ng/mL) (OR=3.4 [1.2 to 9.7]).

Conclusion—
Preeclampsia is associated with decreased levels of ADAMTS13, independently of VWF. This decrease is quantitative, occurs early, and seems to be dependent on inflammation. Our results suggest that ADAMTS13 could participate in the pathophysiology of preeclampsia.