bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fractalkine (CX3CL1) enhances hippocampal N-methyl-d-aspartate receptor (NMDAR) function via d-serine and adenosine receptor type A2 (A2AR) activity
Authors: Scianni Maria , Antonilli Letizia , Chece Giuseppina , Cristalli Gloria , Di Castro Maria Amalia , Limatola Cristina , Maggi Laura 
Published: August 2013

Abstract

Background

N-Methyl-d-aspartate receptors (NMDARs) play fundamental roles in basic brain functions such as excitatory neurotransmission and learning and memory processes. Their function is largely regulated by factors released by glial cells, including the coagonist d-serine. We investigated whether the activation of microglial CX3CR1 induces the release of factors that modulate NMDAR functions.

Methods
We recorded the NMDAR component of the field excitatory postsynaptic potentials (NMDA-fEPSPs) elicited in the CA1 stratum radiatum of mouse hippocampal slices by Shaffer collateral stimulation and evaluated d-serine content in the extracellular medium of glial primary cultures by mass spectrometry analysis.

Results
We demonstrated that CX3CL1 increases NMDA-fEPSPs by a mechanism involving the activity of the adenosine receptor type A2 (A2AR) and the release of the NMDAR coagonist d-serine. Specifically (1) the selective A2AR blocker 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH58261) and the genetic ablation of A2AR prevent CX3CL1 action while the A2AR agonist 5-(6-amino-2-(phenethylthio)-9H-purin-9-yl)-N-ethyl-3,4-dihydroxytetrahydrofuran-2-carboxamide (VT7) mimics CX3CL1 effect, and (2) the selective blocking of the NMDAR glycine (and d-serine) site by 5,7-dicholorokynurenic acid (DCKA), the enzymatic degradation of d-serine by d-amino acid oxidase (DAAO) and the saturation of the coagonist site by d-serine, all block the CX3CL1 effect. In addition, mass spectrometry analysis demonstrates that stimulation of microglia and astrocytes with CX3CL1 or VT7 increases d-serine release in the extracellular medium.

Conclusions
CX3CL1 transiently potentiates NMDAR function though mechanisms involving A2AR activity and the release of d-serine.
The PROBIT approach in estimating the prevalence of wasting: revisiting bias and precision
Authors: Blanton Curtis J , Bilukha Oleg O 
Published: August 2013

Abstract
Background
The PROBIT methodology was presented in the 1995 World Health Organization Technical Report on Anthropometry as an alternative to the standard prevalence based method of measuring malnutrition in children. Theoretically the PROBIT method will always give a smaller standard error than the standard prevalence method in measuring malnutrition. A recent article by Dale et al. assessed the PROBIT method for measuring global acute malnutrition measure and found that the method was biased and the precision was superior only for sample sizes less than 150 when compared to the standard method. In a manner similar to Dale, our study further investigated the bias and precision of the PROBIT method for different sample sizes using simulated populations.

Results
The PROBIT method showed bias for each of the ten simulated populations, but the direction and magnitude of the average bias was changed depending on the simulated population. For a given simulated population, the average bias was relatively constant for all sample sizes drawn. The 95% half-width confidence interval was lower for the PROBIT method than the standard prevalence method regardless of the sample size or simulated population. The absolute difference in the confidence limits showed the most gains for the PROBIT method for the smaller samples sizes, but the ratio of confidence intervals was relatively constant across all sample sizes.

Conclusions
The PROBIT method will provide gains in precision regardless of the sample size, but the method may be biased. The direction and magnitude of the bias depends on the population it is drawn from.
ProAlgaZyme subfraction improves the lipoprotein profile of hypercholesterolemic hamsters, while inhibiting production of betaine, carnitine, and choline metabolites
Authors: Geamanu Andreea , Goja Arvind , Saadat Nadia , Khosla Pramod , Gupta Smiti V 
Published: August 2013

Abstract

Background
Previously, we reported that ProAlgaZyme (PAZ) and its biologically active fraction improved plasma lipids in hypercholesterolemic hamsters, by significantly increasing the high density lipoprotein cholesterol (HDL-C) while reducing non-HDL cholesterol and the ratio of total cholesterol/HDL-C. Moreover, hepatic mRNA expression of genes involved in HDL/reverse cholesterol transport were significantly increased, while cholesteryl ester transfer protein (CETP) expression was partially inhibited. In the current study, we investigated the therapeutic efficacy of the biologically active fraction of PAZ (BaP) on the plasma lipid and plasma metabolomic profiles in diet induced hypercholesterolemic hamsters.

Methods
Fifty male Golden Syrian hamsters were fed a high fat diet for 4 weeks prior to randomization into 6 groups, based on the number of days they received subsequent treatment. Thus animals in T0, T3, T7, T10, T14, and T21 groups received BaP for 0, 3, 7, 10, 14, and 21 days, respectively, as their drinking fluid. Plasma lipids were assayed enzymatically, while real-time reverse transcriptase polymerase chain reaction (RT-PCR) provided the transcription levels of the Apolipoprotein (Apo) A1 gene. The plasma metabolomic profile was determined using 1H nuclear magnetic resonance (NMR) spectroscopy in conjunction with multivariate analysis.

Results
Plasma HDL-C was significantly increased in T3 (P < 0.05) and T21 (P < 0.001), while non-HDL cholesterol was significantly reduced in T3, T7, T10 (P < 0.001) and T14, T21 (P < 0.01). Moreover, the ratio of total cholesterol/HDL-C was significantly lower in all BaP treated groups (P < 0.001) as compared with T0. Quantitative RT-PCR showed an increase in Apo A1 expression in T10 (3-fold) and T21 (6-fold) groups. NMR data followed by multivariate analysis showed a clear separation between T0 and T21 groups, indicating a difference in their metabolomic profiles. Plasma concentrations of metabolites associated with a risk for atherosclerosis and cardiovascular disease, including choline, phosphocholine, glycerol-phosphocholine, betaine and carnitine metabolites were significantly lower in the T21 group.

Conclusion
Treatment with BaP significantly improved the plasma lipid profile by increasing HDL-C and lowering non-HDL cholesterol. In addition, BaP potentially improved the plasma metabolomic profile by reducing the concentration of key metabolites associated with risk for atherosclerosis and cardiovascular disease.
Characterization of a case of follicular lymphoma transformed into B-lymphoblastic leukemia
Authors: Ning Yi , Foss Aubry , Kimball Amy S , Neill Nicholas , Matz Tricia , Schultz Roger 
Published: August 2013

Abstract
Follicular lymphoma (FL) is a common form of non-Hodgkin lymphoma with an ability to transform into a more aggressive disease, albeit infrequently to B-lymphoblastic leukemia/lymphoma. While t(14;18)(q32;q21) has been associated with approximately 90% cases of FL, that alteration alone is insufficient to cause FL and associated mutations are still being elucidated. The transformation of FL to B-lymphoblastic leukemia generally includes the dysregulation of MYC gene expression, typically through IGH rearrangement. Such cases of “double-hit” leukemia/lymphoma with both BCL2 and MYC translocations warrant further study as they are often not identified early, are associated with a poor prognosis, and are incompletely understood in molecular terms. Here we describe a patient with a diagnosis of FL that transformed to B-lymphoblastic leukemia. Detailed cytogenetic characterization of the transformed specimen using karyotype, fluorescence in situ hybridization, microarray and gene rearrangement analyses revealed a complex karyotype comprised principally of whole chromosome or whole arm copy number gains or losses. Smaller, single-gene copy number alterations identified by microarray were limited in number, but included amplification of a truncated EP300 gene and alterations in NEIL1 and GPHN. Analyses defined the presence of an IGH/BCL2 fusion due to a translocation as well as a MYC/IGH fusion due to an insertion, with both rearrangements involving the same IGH allele. The data illustrate the value in characterizing double-hit lymphoma cases with both traditional and novel technologies in the detailed cytogenetic workup.
Identification of key structural elements for neuronal calcium sensor-1 function in the regulation of the temperature-dependency of locomotion in C. elegans
Authors: Martin Victoria M , Johnson James R , Haynes Lee P , Barclay Jeff W , Burgoyne Robert D 
Published: August 2013

Abstract

Background
Intracellular Ca2+ regulates many aspects of neuronal function through Ca2+ binding to EF hand-containing Ca2+ sensors that in turn bind target proteins to regulate their function. Amongst the sensors are the neuronal calcium sensor (NCS) family of proteins that are involved in multiple neuronal signalling pathways. Each NCS protein has specific and overlapping targets and physiological functions and specificity is likely to be determined by structural features within the proteins. Common to the NCS proteins is the exposure of a hydrophobic groove, allowing target binding in the Ca2+-loaded form. Structural analysis of NCS protein complexes with target peptides has indicated common and distinct aspects of target protein interaction. Two key differences between NCS proteins are the size of the hydrophobic groove that is exposed for interaction and the role of their non-conserved C-terminal tails.

Results
We characterised the role of NCS-1 in a temperature-dependent locomotion assay in C. elegans and identified a distinct phenotype in the ncs-1 null in which the worms do not show reduced locomotion at actually elevated temperature. Using rescue of this phenotype we showed that NCS-1 functions in AIY neurons. Structure/function analysis introducing single or double mutations within the hydrophobic groove based on information from characterised target complexes established that both N- and C-terminal pockets of the groove are functionally important and that deletion of the C-terminal tail of NCS-1 did not impair its ability to rescue.

Conclusions
The current work has allowed physiological assessment of suggestions from structural studies on the key structural features that underlie the interaction of NCS-1 with its target proteins. The results are consistent with the notion that full length of the hydrophobic groove is required for the regulatory interactions underlying NCS-1 function whereas the C-terminal tail of NCS-1 is not essential. This has allowed discrimination between two potential modes of interaction of NCS-1 with its targets.
Synthesis of some novel 4-arylidene pyrazoles as potential antimicrobial agents
Authors: Khloya Poonam , Kumar Pawan , Mittal Arpana , Aggarwal Neeraj K , Sharma Pawan K 
Published: August 2013

Abstract

Background
Pyrazole and pyrazolone motifs are well known for their wide range of biological activities such as antimicrobial, anti-inflammatory, and antitumor activities. The incorporation of more than one pharmacophore in a single scaffold is a well known approach for the development of more potent drugs. In the present investigation, a series of differently substituted 4-arylidene pyrazole derivatives bearing pyrazole and pyrazolone pharmacophores in a single scaffold was synthesized.

Results
The synthesis of novel 4-arylidene pyrazole compounds is achieved through Knovenagel condensation between 1,3-diaryl-4-formylpyrazoles and 3-methyl-1-phenyl-1H-pyrazol-5-(4H)-ones in good yields. All compounds were evaluated for their in vitro antimicrobial activity.

Conclusions
A series of 4-arylidene pyrazole derivatives was evaluated for their in vitro antimicrobial activity against two Gram-positive (Bacillus subtilis and Staphylococcus aureus) and two Gram-negative bacteria (Pseudomonas fluorescens and Escherichia coli), as well as two pathogenic fungal strains (Candida albicans and Saccharomyces cerevisiae). The majority of the compounds displayed excellent antimicrobial profile against the Gram-positive (B. subtilis and S. aureus), and some of them are even more potent than the reference drug ciprofloxacin.
New pulse wave measurement method using different hold-down wrist pressures according to individual patient characteristics
Authors: Yoo Seong Ki , Shin Ki Young , Lee Tae Bum , Jin Seung Oh 
Published: August 2013

Abstract
In traditional Chinese and Korean medicine, doctors first observe a patient’s pulse by gently and strongly pressing their fingers onto the wrist, and then make a diagnosis based on the observed pulse waves. The most common method to implement this diagnostic technique is to mechanically extract the pulse waves by applying a fixed range of pressures for all patients. However, this method does not consider the patients individual characteristics such as age, sex, and skin thickness. In the present study, we propose a new method of pulse wave extraction that incorporates the personal characteristics of the patients. This method measures the pulse wave signal at varying hold-down pressures, rather than applying a fixed hold-down pressure for all patients. To compare this new technique with existing methods, we extracted pulse waves from 20 subjects, and then determined the actual applied pressure at each step, the coefficient of floating and sinking pulse (CFS), and the distinction of floating/sinking pulse for each group. Consequently, each subject had a different pressure range in our proposed method, whereas all subjects had a similar pressure range in the existing method. Four of 20 subjects exhibited different floating/sinking pulse patterns due to the value of the first pressure step and the range of hold-down pressures. These four subjects were categorized as overweight based on BMI. In addition, the moving distance of the proposed method was longer than the existing method (p = 0.003, paired t-test), and the correlation coefficient between CFS values of two different methods was 0.321, indicating that there was no correlation.
p53 activation and mitochondria-mediated pathway are involved during hanging death-induced neuronal cell apoptosis in dentate gyrus region of the rat brain
Authors: Khatun Sabana , Chaube Shail K , Bhattacharyya Chandra N 
Published: August 2013

AbstractThe goal of this study was to understand the molecular event in the brain caused by hanging death (HD). Animals were subjected to either cervical dislocation (CD) or HD. Brain was collected at various times (0, 1, 3, 6 and 12 h) after death. Brain expression of p53 and Bax, cytochrome c concentration, caspases activity and DNA fragmentation were analyzed. Compared to that of CD, HD increased p53 and Bax proteins expressions, cytochrome c concentration, caspases activity and DNA fragmentation during the early period (0–6 h) of HD, whereas CD induced necrosis 3 h post- CD and thereafter. These data support that HD induces neuronal cell apoptosis, in part, through mitochondria-mediated pathways. These data also suggest that neuronal apoptosis could be a potential marker and an aid to forensic science of HD.
The genome and transcriptome of Haemonchus contortus, a key model parasite for drug and vaccine discovery
Authors: Laing Roz , Kikuchi Taisei , Martinelli Axel , Tsai Isheng J , Beech Robin N , Redman Elizabeth , Holroyd Nancy , Bartley David J , Beasley Helen , Britton Collette , Curran David , Devaney Eileen , Gilabert Aude , Hunt Martin , Jackson Frank , Johnston Stephanie L , Kryukov Ivan , Li Keyu , Morrison Alison A , Reid Adam J , Sargison Neil , Saunders Gary I , Wasmuth James D , Wolstenholme Adrian , Berriman Matthew , Gilleard John S , Cotton James A 
Published: August 2013

Abstract
Background
The small ruminant parasite Haemonchus contortus is the most widely used parasitic nematode in drug discovery, vaccine development and anthelmintic resistance research. Its remarkable propensity to develop resistance threatens the viability of the sheep industry in many regions of the world and provides a cautionary example of the effect of mass drug administration to control parasitic nematodes. Its phylogenetic position makes it particularly well placed for comparison with the free-living nematode Caenorhabditis elegans and the most economically important parasites of livestock and humans.

Results
Here we report the detailed analysis of a draft genome assembly and extensive transcriptomic dataset for H. contortus. This represents the first genome to be published for a strongylid nematode and the most extensive transcriptomic dataset for any parasitic nematode reported to date. We show a general pattern of conservation of genome structure and gene content between H. contortus and C. elegans, but also a dramatic expansion of important parasite gene families. We identify genes involved in parasite-specific pathways such as blood feeding, neurological function, and drug metabolism. In particular, we describe complete gene repertoires for known drug target families, providing the most comprehensive understanding yet of the action of several important anthelmintics. Also, we identify a set of genes enriched in the parasitic stages of the lifecycle and the parasite gut that provide a rich source of vaccine and drug target candidates.

Conclusions
The H. contortus genome and transcriptome provide an essential platform for postgenomic research in this and other important strongylid parasites.
Prognostic Significance of MTOR Pathway Component Expression in Neuroendocrine Tumors
Authors: Qian Zhi Rong , Ter-Minassian Monica , Chan Jennifer A. , Imamura Yu , Hooshmand Susanne M. , Kuchiba Aya , Morikawa Teppei , Brais Lauren K. , Daskalova Anastassia , Heafield Rachel , Lin Xihong , Christiani David C. , Fuchs Charles S. , Ogino Shuji , Kulke Matthew H. 
Published: August 2013

Purpose Clinical studies have implicated the mechanistic target of rapamycin (serine/threonine kinase; MTOR) pathway in the regulation of neuroendocrine tumor (NET) growth. We explored whether expression of MTOR pathway components has prognostic significance in NET patients. Patients and Methods We evaluated immunohistochemical expression of MTOR and phospho (p) –MTOR; its downstream targets RPS6KB1, RPS6, and EIF4EBP1; and its upstream regulators, in a cohort of 195 archival neuroendocrine tumors. We correlated expression levels with clinical outcomes, after adjusting for other prognostic variables. Results We observed anticipated correlations between expression of upstream components of the MTOR pathway and their downstream targets. Expression of PIK3CA, MTOR, or p-EIF4EBP1 was associated with high MKI67 (Ki-67) labeling index. We failed to identify clinical correlations associated with expression of the upstream regulators TSC1, TSC2, AKT, p-AKT, PDPK1, PTEN, PIK3R1, or PIK3CA. In contrast, high expression of MTOR or its activated downstream targets p-RPS6KB1, p-RPS6, or p-EIF4EBP1 was associated with adverse clinical outcomes. Conclusion Our observations suggest that expression of MTOR or its downstream targets may be adverse prognostic factors in neuroendocrine tumors.
German Adjuvant Intergroup Node-Positive Study: A Phase III Trial to Compare Oral Ibandronate Versus Observation in Patients With High-Risk Early Breast Cancer
Authors: von Minckwitz Gunter , Möbus Volker , Schneeweiss Andreas , Huober Jens , Thomssen Christoph , Untch Michael , Jackisch Christian , Diel Ingo J. , Elling Dirk , Conrad Bettina , Kreienberg Rolf , Müller Volkmar , Lück Hans-Joachim , Bauerfeind Ingo , Clemens Michael , Schmidt Marcus , Noeding Stefanie , Forstbauer Helmut , Barinoff Jana , Belau Antje , Nekljudova Valentina , Harbeck Nadia , Loibl Sibylle 
Published: August 2013

Purpose Bisphosphonates prevent skeletal-related events in patients with metastatic breast cancer. Their effect in early breast cancer is controversial. Ibandronate is an orally and intravenously available amino-bisphosphonate with a favorable toxicity profile. It therefore qualifies as potential agent for adjuvant use. Patients and Methods The GAIN (German Adjuvant Intergroup Node-Positive) study was an open-label, randomized, controlled phase III trial with a 2 × 2 factorial design. Patients with node-positive early breast cancer were randomly assigned 1:1 to two different dose-dense chemotherapy regimens and 2:1 to ibandronate 50 mg per day orally for 2 years or observation. In all, 2,640 patients and 728 events were estimated to be required to demonstrate an increase in disease-free survival (DFS) by ibandronate from 75% to 79.5% by using a two-sided α = .05 and 1-β of 80%. We report here the efficacy analysis for ibandronate, which was released by the independent data monitoring committee because the futility boundary was not crossed after 50% of the required DFS events were observed. Results Between June 2004 and August 2008, 2,015 patients were randomly assigned to ibandronate and 1,008 to observation. Patients randomly assigned to ibandronate showed no superior DFS or overall survival (OS) compared with patients randomly assigned to observation (DFS: hazard ratio, 0.945; 95% CI, 0.768 to 1.161; P = .589; OS: HR, 1.040; 95% CI, 0.763 to 1.419; P = .803). DFS was numerically longer if ibandronate was used in patients younger than 40 years or older than 60 years compared with patients age 40 to 59 years (test for interaction P = .093). Conclusion Adjuvant treatment with oral ibandronate did not improve outcome of patients with high-risk early breast cancer who received dose-dense chemotherapy.
Brivanib in Patients With Advanced Hepatocellular Carcinoma Who Were Intolerant to Sorafenib or for Whom Sorafenib Failed: Results From the Randomized Phase III BRISK-PS Study
Authors: Llovet Josep M. , Decaens Thomas , Raoul Jean-Luc , Boucher Eveline , Kudo Masatoshi , Chang Charissa , Kang Yoon-Koo , Assenat Eric , Lim Ho-Yeong , Boige Valerie , Mathurin Philippe , Fartoux Laetitia , Lin Deng-Yn , Bruix Jordi , Poon Ronnie T. , Sherman Morris , Blanc Jean-Frédéric , Finn Richard S. , Tak Won-Young , Chao Yee , Ezzeddine Rana , Liu David , Walters Ian , Park Joong-Won 
Published: August 2013

Purpose Brivanib is a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor receptors implicated in tumorigenesis and angiogenesis in hepatocellular carcinoma (HCC). An unmet medical need persists for patients with HCC whose tumors do not respond to sorafenib or who cannot tolerate it. This multicenter, double-blind, randomized, placebo-controlled trial assessed brivanib in patients with HCC who had been treated with sorafenib. Patients and Methods In all, 395 patients with advanced HCC who progressed on/after or were intolerant to sorafenib were randomly assigned (2:1) to receive brivanib 800 mg orally once per day plus best supportive care (BSC) or placebo plus BSC. The primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response rate (ORR), and disease control rate based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) and safety. Results Median OS was 9.4 months for brivanib and 8.2 months for placebo (hazard ratio [HR], 0.89; 95.8% CI, 0.69 to 1.15; P = .3307). Adjusting treatment effect for baseline prognostic factors yielded an OS HR of 0.81 (95% CI, 0.63 to 1.04; P = .1044). Exploratory analyses showed a median time to progression of 4.2 months for brivanib and 2.7 months for placebo (HR, 0.56; 95% CI, 0.42 to 0.76; P < .001), and an mRECIST ORR of 10% for brivanib and 2% for placebo (odds ratio, 5.72). Study discontinuation due to treatment-related adverse events (AEs) occurred in 61 brivanib patients (23%) and nine placebo patients (7%). The most frequent treatment-related grade 3 to 4 AEs for brivanib included hypertension (17%), fatigue (13%), hyponatremia (11%), and decreased appetite (10%). Conclusion In patients with HCC who had been treated with sorafenib, brivanib did not significantly improve OS. The observed benefit in the secondary outcomes of TTP and ORR warrants further investigation.