bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatic Veno‐Occlusive Disease in a Kidney Transplant Patient: Case Report and Review of the Literature
Authors: Jalandhara Nishant , Thakor Pratapji , Goswami Monica , Zhang Rubin 
Published: May 2011

AbstractVeno‐occlusive disease (VOD) of the liver is an extremely rare complication of azathioprine (AZT) use in patients with kidney transplants (KTs). Although VOD is frequently seen in bone marrow transplant patients, so far only 24 cases have been reported in KT patients. Our case adds to the available data on the disease, and we also reviewed the published data on this entity to establish the characteristics of VOD in the setting of KT. Our case highlights the importance of this potentially life‐threatening complication and provides an overview of VOD in KT patients.
Modulation of neurite outgrowth by activation of calcium‐permeable kainate receptors expressed by rat nociceptive‐like dorsal root ganglion neurons
Authors: Joseph Donald J. , Williams Damian J. , MacDermott Amy B. 
Published: May 2011

AbstractNeurite outgrowth is a fundamental step in establishing proper neuronal connections in the developing central nervous system. Dynamic control of outgrowth has been attributed to changes in growth cone Ca2+ levels in response to extracellular cues. Here we have investigated a possible role for Ca2+ permeable kainate (KA) receptors in regulating neurite outgrowth of nociceptive‐like dorsal root ganglion (DRG) neurons. To identify KA receptor subunits likely to be involved, we used quantitative RT‐PCR on acutely dissociated DRG and dorsal horn neurons. DRG neurons expressed more GluK1, particularly the GluK1b spice variant, than dorsal horn neurons. Conversely, dorsal horn neurons expressed more GluK2, particularly GluK2a, than DRG neurons. Further, an RNA editing assay indicated that the majority of GluK1 and GluK2 mRNA transcripts in DRG were unedited. Imaging Ca2+ transients following application of a KA receptor agonist to DRG and dorsal horn co‐cultures revealed increases in intracellular Ca2+ in the growth cones of DRG neurons. In the majority of cases, this increase in Ca2+ was partly or completely blocked by Joro spider toxin (JSTX), an antagonist for Ca2+‐permeable AMPA and KA receptors. Treatment of DRG/dorsal horn co‐cultures with KA for 18 hours suppressed neurite outgrowth while application of the rapidly desensitizing KA receptor agonist SYM 2081, the competitive AMPA/KA receptor antagonist, CNQX, and JSTX or philanthotoxin enhanced neurite outgrowth and prevented KA effects on neurite outgrowth. Thus, Ca2+ entry through KA receptors at the growth cone of DRG neurons may be an important regulator of neurite outgrowth. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 71: 818–835, 2011
Neurotransmitter phenotype plasticity: An unexpected mechanism in the toolbox of network activity homeostasis
Authors: Demarque Michaël , Spitzer Nicholas C. 
Published: May 2011

AbstractThe transmitter phenotype of a neuron has long been thought to be stable for the lifespan. Much as eyes have one color and do not change it over time, neurons have been thought to have one neurotransmitter and retain it for their lifetime. Both principles, exclusivity and stability, are challenged by recent data. More and more neurons in different regions of the brain appear to coexpress two or more neurotransmitters. Moreover, the profile of neurotransmitter expression of a given neuron has been shown to change over time, both during development and in response to changes in activity. The present review summarizes recent studies of this neurotransmitter phenotype plasticity (NPP). Homeostatic mechanisms of plasticity are aimed at maintaining the system within a functional range. They appear to be critical for optimal network operations and have been thought to operate largely by regulating intrinsic excitability, synapse number and synaptic strength. NPP provides a new and unexpected level of regulation of network homeostasis. We propose that it provides the basis for NT coexpression and discuss emerging issues and new questions for further studies in coming years. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 22–32, 2012
Timescales of hydrolimnological change in floodplain lakes of the Peace‐Athabasca Delta, northern Alberta, Canada
Authors: Wiklund Johan A. , Hall Roland I. , Wolfe Brent B. 
Published: May 2011

ABSTRACTRepeated measurements over 3 years (2003–2005) were made on a series of lakes along a hydrological gradient in the Peace‐Athabasca Delta (PAD), Canada, to characterize the role of river flooding on limnological conditions of northern floodplain lakes and to identify the patterns and timescales of limnological change after flooding. River floodwaters elevate concentrations of suspended sediment, total phosphorus (TP), SO4 and dissolved silica (DSi) and reduce concentrations of total Kjeldahl nitrogen (TKN), dissolved organic carbon (DOC) and most ions, which leads to increased limnological homogeneity among lakes. After flooding, limnological changes occur at two distinct timescales. In the weeks to months after flooding, water clarity increases as suspended sediments and TP settle out of the water column, but concentrations of DOC, SO4, TKN and ions do not change appreciably. However, in the absence of flooding for many years to decades, evaporative concentration leads to an increase in most nutrients, DOC and ions. Contrary to a prevailing paradigm, these results suggest that regular flooding is not required to maintain high nutrient concentrations. In light of anticipated declines in river discharge, we predict that limnological conditions in the southern Athabasca sector will become increasingly less dominated by the short‐term effects of flooding, and resemble nutrient‐ and solute‐rich lakes in the northern Peace sector that are infrequently flooded. Copyright © 2011 John Wiley & Sons, Ltd.
Quantitative gel electrophoresis: New records in precision by elaborated staining and detection protocols
Authors: Deng Xi , Schröder Simone , Redweik Sabine , Wätzig Hermann 
Published: May 2011

AbstractGel electrophoresis (GE) is a very common analytical technique for proteome research and protein analysis. Despite being developed decades ago, there is still a considerable need to improve its precision. Using the fluorescence of Colloidal Coomassie Blue ‐stained proteins in near‐infrared (NIR), the major error source caused by the unpredictable background staining is strongly reduced. This result was generalized for various types of detectors. Since GE is a multi‐step procedure, standardization of every single step is required. After detailed analysis of all steps, the staining and destaining were identified as the major source of the remaining variation. By employing standardized protocols, pooled percent relative standard deviations of 1.2–3.1% for band intensities were achieved for one‐dimensional separations in repetitive experiments. The analysis of variance suggests that the same batch of staining solution should be used for gels of one experimental series to minimize day‐to‐day variation and to obtain high precision.
Haplotyping of putative microRNA‐binding sites in the SNAP‐25 gene
Authors: Kovacs‐Nagy Reka , Sarkozy Peter , Hu Jimmy , Guttman Andras , Sasvari‐Szekely Maria , Ronai Zsolt 
Published: May 2011

AbstractSynaptosomal‐associated protein 25 (SNAP‐25) plays a crucial role in exocitosis. Single nucleotide polymorphisms (rs3746544 and rs1051312) in the 3′ un‐translated region of the SNAP‐25 gene have been described to be in association with attention‐deficit hyperactivity disorder. As the disease affects millions of children world‐wide, understanding the genetic background of attention‐deficit hyperactivity disorder is of crucial importance. Efficient and reliable PCR‐RFLP protocols were elaborated for the genotyping of the rs3746544 and rs1051312 SNPs employing a high‐throughput capillary electrophoresis method for fragment analysis. A novel real‐time PCR‐based technique was used applying sequence specific TaqMan probes to haplotype the two SNPs, and the G–C haplotype could not be detected in a large Caucasian population (N=1376). These findings have been confirmed by molecular biology tools as well as by the PHASE Bayesian computational approach. In silico analyses have suggested that the two SNPs might alter microRNA binding and thus have an effect on SNAP‐25 production. We have demonstrated that this biological information can be revealed only by direct haplotype analysis emphasizing the importance of our novel molecular haplotye analysis protocol. Results of the study of the two SNPs might shed light on the association of SNAP‐25 variants and pathological phenotypes at the molecular level.
Proteomic biomarker discovery: It's more than just mass spectrometry
Authors: Blonder Josip , Issaq Haleem J. , Veenstra Timothy D. 
Published: May 2011

AbstractThe previous decade witnessed an enormous number of studies with the singular goal of identifying protein biomarkers for diseases such as cancer. A large majority of these studies have focused on comparative studies of serum or plasma obtained from disease‐affected and control patients. In these studies, proteins identified in the samples using MS were compared with the hope that differences between samples would reveal useful biomarkers. Unfortunately, finding clinically relevant biomarkers has often been elusive and frustrating. As with most research efforts, both successes and failures, much has been learned about what strategies work and which do not. Part of the problem can be attributed to underestimating the effort required to discover novel biomarkers and depending too heavily on MS analysis of peripheral blood samples. Fortunately, the future for biomarker discovery still appears bright. MS technology continues to increase in sensitivity, throughput, and accuracy while novel types of samples and clever experimental designs coupled with innovative bioinformatics will make this vision of routine biomarker discovery a reality. To achieve ultimate success is going to require concomitant application of a number of different technologies, all providing the information necessary for discovering and validating clinically useful biomarkers.
Effect of hydroxytyrosol‐rich preparations on phenolic‐linked antioxidant activity of seeds
Authors: Yangui Thabèt , Sayadi Sami , Chakroun Hanen , Dhouib Abdelhafidh 
Published: May 2011

AbstractHydroxytyrosol‐rich extract (HRE) and hydroxytyrosol‐rich olive mill wastewater (HROMW) were used as exogenous growth enhancers to stimulate tomato seedling vigor. The tomato seeds soaking in 10% w/v HROMW or HRE solutions were optimum in maximally enhancing seedling performance according to biochemical seed vigor parameters. Biochemical parameters as the average glucose‐6‐phosphate dehydrogenase (G6PDH) activity in HRE‐treated seeds (915.11 nmoles min−1 mg−1 protein) was higher than control (629.58 nmoles min−1 mg−1 protein) and correlated with the increased phenolic content (3530 μg g−1 fw) and 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH)‐based antioxidant activity (70.60%), respectively. Some key enzymes, guaiacol peroxidase (GPX) (6100.65 nmoles min−1 mg−1 protein) and catalase (2.04 μmoles min−1 mg−1 protein), were also higher in response to treatments and correlated with enhanced phenolic content and antioxidant activity. This study supports the hypothesis that the exogenous phenolic application stimulates the pentose phosphate pathway through an over‐expression of endogenous phenolic synthesis and an increase in free‐radical scavenging antioxidant activity. Therefore, the current study indicates the enhancement of seed vigor by HRE especially and HROMW as reflected by the stimulation of biochemical responses.
Functional brain network efficiency predicts intelligence
Authors: Langer Nicolas , Pedroni Andreas , Gianotti Lorena R.R. , Hänggi Jürgen , Knoch Daria , Jäncke Lutz 
Published: May 2011

AbstractThe neuronal causes of individual differences in mental abilities such as intelligence are complex and profoundly important. Understanding these abilities has the potential to facilitate their enhancement. The purpose of this study was to identify the functional brain network characteristics and their relation to psychometric intelligence. In particular, we examined whether the functional network exhibits efficient small‐world network attributes (high clustering and short path length) and whether these small‐world network parameters are associated with intellectual performance. High‐density resting state electroencephalography (EEG) was recorded in 74 healthy subjects to analyze graph‐theoretical functional network characteristics at an intracortical level. Ravens advanced progressive matrices were used to assess intelligence. We found that the clustering coefficient and path length of the functional network are strongly related to intelligence. Thus, the more intelligent the subjects are the more the functional brain network resembles a small‐world network. We further identified the parietal cortex as a main hub of this resting state network as indicated by increased degree centrality that is associated with higher intelligence. Taken together, this is the first study that substantiates the neural efficiency hypothesis as well as the Parieto‐Frontal Integration Theory (P‐FIT) of intelligence in the context of functional brain network characteristics. These theories are currently the most established intelligence theories in neuroscience. Our findings revealed robust evidence of an efficiently organized resting state functional brain network for highly productive cognitions. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.
Dichloroacetate inhibits neuroblastoma growth by specifically acting against malignant undifferentiated cells
Authors: Vella Serena , Conti Matteo , Tasso Roberta , Cancedda Ranieri , Pagano Aldo 
Published: May 2011

AbstractThe small, water soluble molecule Dichloroacetate (DCA) is recently arousing lively interests in the field of cancer therapy for it has been shown to be able to inhibit the growth of human tumors acting specifically on the mitochondria of cancer cells without perturbing the physiology of nonmalignant cells. Neuroblastoma was one of the tumor types on which DCA was considered ineffective as it is composed of cells with few recognized mitochondrial anomalies. Neuroblastoma, however, is composed of different cell types in terms of metabolism, phenotype and malignant potential. Despite the above prediction, in this work, we show that (i) DCA exhibits an unexpected anticancer effect on NB tumor cells and (ii) this effect is selectively directed to very malignant NB cells, whereas the more differentiated/less malignant NB cells are refractory to DCA treatment. This result supports the need of a detailed investigation of DCA anticancer properties against this tumor type with the final aim of its possible use as therapeutic agent.
YC‐1 rescues cancer cachexia by affecting lipolysis and adipogenesis
Authors: Chung Tsai‐Hua , Yen‐Ping Kuo Mark , Chen Jen‐Kun , Huang Dong‐Ming 
Published: May 2011

AbstractLoss of adipose tissue, primarily due to increased lipolysis but also to an impairment of adipogenesis, is a key feature of weight loss in cancer cachexia. Because of the myriad pathogenic signaling pathways essential for atrophy of adipose tissue, effective therapeutic agents for cachectic adipose loss are lacking and urgently needed. The authors evaluated the effects of YC‐1 on adipogenesis of 3T3‐L1 preadipocytes, TNF‐α‐ and tumor‐cell‐induced lipolysis in 3T3‐L1 adipocytes, and cachectic weight loss in colon‐26 adenocarcinoma‐bearing mice because YC‐1 has been shown to possess versatile pharmacological actions, including anticancer activity. It was found that YC‐1 promotes the differentiation of 3T3‐L1 preadipocytes into adipocytes through activation of Akt and extracellular signal‐regulated kinase (ERK) signaling pathways as well as activation of several adipogenic mediators, such as peroxisome proliferator‐activated receptor γ (PPARγ), insulin receptor α (IRα), insulin receptor substrate‐3 (IRS‐3) and glucose transporter‐4 (GLUT‐4). In the in vitro lipolysis models, YC‐1 attenuates TNF‐α‐induced lipolysis of adipocytes by antagonizing TNF‐α‐mediated activation of ERK and downregulation of perilipin (PLIN). It was also found that YC‐1 inhibits colon‐26 adenocarcinoma cell‐induced lipolysis of 3T3‐L1 adipocytes. Moreover, YC‐1 effectively rescues cachectic weight loss in colon‐26 adenocarcinoma‐bearing mice by blocking lipolysis, involving insulin. Taken together the results show that YC‐1 with its anticancer and anticachexia talents is highly worth developing as a novel agent for cancer therapy.
p53 mutation is common in microsatellite stable, BRAF mutant colorectal cancers
Authors: Bond Catherine E. , Umapathy Aarti , Ramsnes Ingunn , Greco Sonia A. , Zhen Zhao Zhen , Mallitt Kylie‐Ann , Buttenshaw Ron L. , Montgomery Grant W. , Leggett Barbara A. , Whitehall Vicki L.J. 
Published: May 2011

AbstractThe majority of “serrated pathway” colorectal cancers have mutation of the BRAF oncogene and display the CpG island methylator phenotype (CIMP). Half these cancers have microsatellite instability (MSI) and an excellent prognosis. In the absence of MSI (microsatellite stable, MSS), BRAF mutation has been associated with a particularly poor prognosis. “Traditional pathway” cancers are BRAF wild type. Mutation of p53 is common and this correlates with advanced stage. We therefore hypothesized that p53 mutation would be common in MSS/BRAF mutant colorectal cancer. One thousand and eighty‐one colorectal cancers were screened for BRAF mutation to identify two BRAF mutant study groups (MSI: n = 77; MSS: n = 69) and a BRAF wild type control group (n = 101). These were screened for p53 mutation by high resolution melt analysis and classified for CIMP and MGMT methylation by quantitative methylation specific PCR. Molecular data were compared to patient age, gender, tumor location and stage. p53 was mutated significantly more frequently in MSS/BRAF mutant (28/69, 40.6%) compared to MSI/BRAF mutant cancers (13/77, 16.9%), but this mutation rate did not differ from MSS/BRAF wild type cancers (47/101, 46.5%)(p < 0.0001). CIMP was less common in MSS/BRAF mutant (26/47, 55.3%) compared to MSI/BRAF mutant cancers (41/54, 75.9%), but was more common than in MSS/BRAF wild type cancers (3/85, 3.5%) (p < 0.0001). MSS/BRAF mutant cancers were more commonly proximal (38/54, 70.3%), but were similar to MSS/BRAF wild type cancers in terms of patient age, gender distribution and stage at presentation. MSS/BRAF mutant cancers share molecular and clinical features of both the serrated and traditional pathways of colorectal tumorigenesis.
Human dendritic cells efficiently phagocytose adenoviral oncolysate but require additional stimulation to mature
Authors: Schierer Stephan , Hesse Andrea , Knippertz Ilka , Kaempgen Eckhart , Baur Andreas S. , Schuler Gerold , Steinkasserer Alexander , Nettelbeck Dirk M. 
Published: May 2011

AbstractOncolytic adenoviruses are emerging agents for treatment of cancer by tumor‐restricted virus infection and cell lysis. Clinical trials have shown that oncolytic adenoviruses are well tolerated in patients but also that their antitumor activity needs improvement. A promising strategy toward this end is to trigger systemic and prolonged antitumor immunity by adenoviral oncolysis. Antitumor immune activation depends in large part on antigen presentation and T cell activation by dendritic cells (DCs). Thus, it is likely that the interaction of lysed tumor cells with DCs is a key determinant of such “oncolytic vaccination.” Our study reveals that human DCs effectively phagocytose melanoma cells at late stages of oncolytic adenovirus infection, when the cells die showing preferentially features of necrotic cell death. Maturation, migration toward CCL19 and T cell stimulatory capacity of DCs, crucial steps for immune induction, were, however, not induced by phagocytosis of oncolysate, but could be triggered by a cytokine maturation cocktail. Therefore, oncolytic adenoviruses and adenoviral oncolysate did not block DC maturation, which is in contrast to reports for other oncolytic viruses. These results represent a rationale for inserting immunostimulatory genes into oncolytic adenovirus genomes to assure critical DC maturation. Indeed, we report here that adenoviral transduction of melanoma cells with CD40L during oncolysis triggers the maturation of human DCs with T cell stimulatory capacity similar to DCs matured by cytokines. We conclude that triggering and shaping DC‐induced antitumor immunity by oncolytic adenoviruses “armed” with immunostimulatory genes holds promise for improving the therapeutic outcome of viral oncolysis in patients.
PAR1 plays a role in epithelial malignancies: Transcriptional regulation and novel signaling pathway
Authors: Bar‐Shavit Rachel , Turm Hagit , Salah Zaidoun , Maoz Myriam , Cohen Irit , Weiss Einat , Uziely Beatrice , Grisaru‐Granovsky Sorina 
Published: May 2011

AbstractProtease‐activated receptor1 (PAR1) is the first and prototype member of an established PAR family comprising four members. The role of PAR1 in tumor biology has been established, and is characterized by a consistent direct correlation between overexpression of its levels and epithelial tumor aggressiveness. We have found that high expression of the human Par1 (hPar1) gene in epithelial tumors is controlled largely at the transcriptional level. This led us to assign Egr‐1, a transcription activator, as an inducer of hPar1, and p53, a tumor suppressor gene, as an inhibitor, both acting to achieve fine tuning of hPar1 in prostate carcinoma. High PAR1 levels maintain prosurvival signals in tumor cells while silencing or ablation of the gene induce apoptosis. Studies of our hPar1 transgenic mice, which overexpress hPar1 in the mammary glands, revealed a novel PAR1‐induced β‐catenin stabilization function. The components connecting PAR1 to β‐catenin stabilization have been determined, assigning at first Gα13 as a selective immediate component. The PAR1‐Gα13 axis recruits disheveled (DVL), an upstream signaling partner of the canonical Wnt signaling pathway. Silencing of DVL by siRNA‐DVL potently abrogates PAR1‐induced β‐catenin stabilization, demonstrating its critical role in the process. We, thus, propose that transcriptional regulation of hPar1 gene over expression in epithelia malignancies initiates a novel signaling pathway, directly connecting to β‐catenin stabilization, a core event in both tumorigenesis and developmental processes. © 2011 IUBMB IUBMB Life, 63(6): 397–402, 2011
Serine and metalloprotease signaling through PAR1 in arterial thrombosis and vascular injury
Authors: Koukos Georgios , Sevigny Leila , Zhang Ping , Covic Lidija , Kuliopulos Athan 
Published: May 2011

AbstractThrombin‐dependent platelet activation has been shown to be important in the setting of angioplasty and stenting, which may cause ischemic complications including acute myocardial infarction and death. Inhibitors of the high‐affinity thrombin receptor, protease‐activated receptor 1 (PAR1), are now being evaluated in clinical trials for safety and efficacy in patients with atherothrombotic disease. However, it is unknown whether chronic inhibition of PAR1 in these large patient populations will have beneficial or possibly adverse effects on other biologic processes involved in blood vessel homeostasis and the response to vascular injury. Most recently, PAR1 was found to be cleaved at a distinct site by matrix metalloprotease‐1 (MMP‐1) to create a longer tethered ligand, which activates a distinct spectrum of G protein pathways in platelets. The differential activation by serine proteases such as thrombin and the metalloprotease MMP‐1, places the protease receptor PAR1 at the junction of two major protease classes critically involved in thrombosis, matrix remodeling, and the response to vascular injury. © 2011 IUBMB IUBMB Life, 63(6): 412–418, 2011