bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishing a relationship between prolactin and altered fatty acid β-Oxidation via carnitine palmitoyl transferase 1 in breast cancer cells
Authors: Linher-Melville Katja , Zantinge Stephanie , Sanli Toran , Gerstein Hertzel , Tsakiridis Theodoros , Singh Gurmit 
Published: February 2011

Abstract

Background
Mammary carcinomas have been associated with a high-fat diet, and the rate of breast cancer in overweight post-menopausal women is up to 50% higher than in their normal-weight counterparts. Epidemiological studies suggest that prolactin (PRL) plays a role in the progression of breast cancer. The current study examined breast cancer as a metabolic disease in the context of altered fatty acid catabolism by examining the effect of PRL on carnitine palmitoyl transferase 1 (CPT1), an enzyme that shuttles long-chain fatty acids into the mitochondrial matrix for β-oxidation. The effect of PRL on the adenosine 5'-monophosphate-activated protein kinase (AMPK) energy sensing pathway was also investigated.

Methods
MCF-7 and MDA-MB-231 breast cancer cells and 184B5 normal breast epithelial cells treated with 100 ng/ml of PRL for 24 hr were used as in vitro models. Real-time PCR was employed to quantify changes in mRNA levels and Western blotting was carried out to evaluate changes at the protein level. A non-radioactive CPT1 enzyme activity assay was established and siRNA transfections were performed to transiently knock down specific targets in the AMPK pathway.

Results
PRL stimulation increased the expression of CPT1A (liver isoform) at the mRNA and protein levels in both breast cancer cell lines, but not in 184B5 cells. In response to PRL, a 20% increase in CPT1 enzyme activity was observed in MDA-MB-231 cells. PRL treatment resulted in increased phosphorylation of the α catalytic subunit of AMPK at Thr172, as well as phosphorylation of acetyl-CoA carboxylase (ACC) at Ser79. A siRNA against liver kinase B1 (LKB1) reversed these effects in breast cancer cells. PRL partially restored CPT1 activity in breast cancer cells in which CPT1A, LKB1, or AMPKα-1 were knocked down.

Conclusions
PRL enhances fatty acid β-oxidation by stimulating CPT1 expression and/or activity in MCF-7 and MDA-MB-231 breast cancer cells. These PRL-mediated effects are partially dependent on the LKB1-AMPK pathway, although the regulation of CPT1 is also likely to be influenced by other mechanisms. Ultimately, increased CPT1 enzyme activity may contribute to fueling the high energy demands of cancer cells. Targeting metabolic pathways that are governed by PRL, which has already been implicated in the progression of breast cancer, may be of therapeutic benefit.
Early blood glucose profile and neurodevelopmental outcome at two years in neonatal hypoxic-ischaemic encephalopathy
Authors: Nadeem Montasser , Murray Deirdre M , Boylan Geraldine B , Dempsey Eugene M , Ryan Cornelius A 
Published: February 2011

Abstract

Background
To examine the blood glucose profile and the relationship between blood glucose levels and neurodevelopmental outcome in term infants with hypoxic-ischaemic encephalopathy.

Methods
Blood glucose values within 72 hours of birth were collected from 52 term infants with hypoxic-ischaemic encephalopathy. Hypoglycaemia [< 46.8 mg/dL (2.6 mmol/L)] and hyperglycaemia [> 150 mg/dL (8.3 mmol/L)] were correlated to neurodevelopmental outcome at 24 months of age.

Results
Four fifths of the 468 blood samples were in the normoglycaemic range (392/468:83.8%). Of the remaining 76 samples, 51.3% were in the hypoglycaemic range and (48.7%) were hyperglycaemic. A quarter of the hypoglycaemic samples (28.2%:11/39) and a third of the hyperglycaemic samples (32.4%:12/37) were recorded within the first 30 minutes of life. Mean (SD) blood glucose values did not differ between infants with normal and abnormal outcomes [4.89(2.28) mmol/L and 5.02(2.35) mmol/L, p value = 0.15] respectively. In term infants with hypoxic-ischaemic encephalopathy, early hypoglycaemia (between 0-6 hours of life) was associated with adverse outcome at 24 months of age [OR = 5.8, CI = 1.04-32)]. On multivariate analysis to adjust for grade of HIE this association was not statistically significant. Late hypoglycaemia (6-72 hours of life) was not associated with abnormal outcome [OR = 0.22, CI (0.04-1.14)]. The occurrence of hyperglycaemia was not associated with adverse outcome.

Conclusion
During the first 72 hours of life, blood glucose profile in infants with hypoxic-ischaemic encephalopathy varies widely despite a management protocol. Early hypoglycaemia (0-6 hours of life) was associated with severe HIE, and thereby; adverse outcome.
The pandemic (H1N1) 2009 influenza virus is resistant to mannose-binding lectin
Authors: Tokunaga Hirotoshi , Ushirogawa Hiroshi , Ohuchi Masanobu 
Published: February 2011

Abstract

Background
Mannose-binding lectin (MBL) is an important component of innate immunity because it promotes bacterial clearance and neutralization of human influenza A viruses. Since a majority of humans have no neutralizing antibody against the pandemic (H1N1) 2009 influenza (pandemic 2009) virus, innate immunity may be crucial and MBL susceptibility may therefore influence viral pathogenesis.

Results
We examined MBL susceptibility of influenza A viruses and observed that the pandemic 2009 virus was resistant to MBL, whereas all seasonal influenza A viruses tested were susceptible. The mortality of mice infected with a seasonal H1N1 influenza virus was evidently enhanced on transient blockage of MBL activity by simultaneous inoculation of mannan, whereas mannan inoculation had no effect on mice infected with a pandemic 2009 virus. This indicates that MBL protects mice against infection with the seasonal virus but not against that with the pandemic 2009 virus.

Conclusions
These results indicate that the pandemic 2009 virus is not susceptible to MBL, an important component of innate immunity.
Administration of α-galactosylceramide impairs the survival of dendritic cell subpopulations in vivo
Authors: Simkins Helen M A , Hyde Evelyn , Farrand Kathryn J , Ong Monique L , Degli-Esposti Mariapia A , Hermans Ian F , Ronchese Franca 
Published: February 2011

ABSTRACTIn this study, we examine whether recognition of α-GalCer presented on CD1d-expressing DCs and B cells in vivo elicits the cytotoxic activity of iNKT cells and elimination of α-GalCer-presenting cells. We report that i.v. injection of α-GalCer induced a decrease in the percentage and number of splenic CD8+Langerin+ DCs, while CD8– DCs were not affected. The decline in CD8+ DC numbers was clearly detectable by 15 h after α-GalCer injection, was maximal at 24–48 h, returned to normal by day 7, and was accompanied by a reduced cross-presentation of OVA protein given i.v. to specific CD8+ T cells in vitro. The decrease in the numbers of CD8+ DCs required iNKT cells but was independent of perforin, Fas, or IFN-γ, as it was observed in mice deficient in each of these molecules. In contrast, treatment with a TNF-α-neutralizing antibody was effective at reducing the decline in CD8+ DC numbers and DC activation. Treatment with immunostimulatory CpG ODN also resulted in DC activation and a decreased number of CD8+ DCs; however, the decline in DC number was a result of down-regulation of CD11c and CD8 and did not require iNKT cells or TNF-α. Although CD8+Langerin+ DCs appeared to be selectively affected by α-GalCer treatment, they were not required for early iNKT cell responses, as their prior depletion did not prevent the increase in serum TNF-α and IL-4 observed after α-GalCer treatment. Thus, iNKT cells regulate the survival of CD8+ DCs through a mechanism that does not appear to involve direct cell killing.
Oxidation of Guanosine to the Imidazolone Derivative via Proton-coupled Electron Transfer to Hydroperoxy Radical Derived from Superoxide
Authors: Murakami Hiroya , Esaka Yukihiro , Nakayama Tatsushi , Uno Bunji 
Published: February 2011

Abstract
Oxidation of guanosine (G) with electrochemically generated superoxide (O2•−) leads to the imidazolone (Iz) derivative as a single-electron oxidation product of G. A crucial step in the mechanism of the oxidation is the proton-coupled electron transfer (PCET) from G to the hydroperoxy radical (HO2•) that is derived from O2•−.
Intercalation of Methylene Blue in a High-Charge Calcium Montmorillonite — An Indication of Surface Charge Determination
Authors: Li Zhaohui , Wang Chih-Jen , Jiang Wei-Teh 
Published: February 2011

The suitability and applicability of using Methylene Blue (MB), a cationic dye, for cation-exchange capacity (CEC) and specific surface area (SSA) determinations has been studied extensively. Although many workers have reported satisfactory results between the CEC determined by the MB method and other methods, large discrepancies among CEC values determined by different methods are also found in the literature. The work reported herein was focused at elucidating the interlayer configuration of adsorbed/intercalated MB in SAz-1, a high-charge montmorillonite, using MB adsorption, exchangeable cation desorption, counterion (Cl−) adsorption, X-ray diffraction (XRD) and Fourier-transform infrared (FT-IR) analyses. A complete balance between the amount of MB cation adsorbed and that of exchangeable cations desorbed at a 1:1 charge ratio for MB uptake by SAz-1 indicated that cation-exchange was the most important mechanism in this case together with supplementary hydrogen bonding. The adsorbed MB molecules associated into dimers and were orientated in the interlayer in a nearly vertical configuration, with the sulphur atom keyed onto the surface. In a vertical orientation, the MB dimer occupies a projected area of 120–130 Å2, similar to the surface area of 130 Å2 previously assumed from SSA determinations for the horizontally aligned MB molecule. Hence, it is the charge density rather than the horizontal configuration of the MB molecules that controls the MB adsorption capacity. As such, the CEC determination of swelling clays using the MB adsorption method is justified. However, SSA determination by the MB method is correct only if the charge density is less than the projected area of 120–130 Å2 for an MB dimer. This suggests that the previous assumption of the adsorption of a horizontally orientated MB molecule onto the surface of clay minerals is questionable.
Operation Theory of Wind Pumps (2)
Authors: Siddig Mohammed Hashim 
Published: February 2011

Following on a preceding paper of the same title [1], and the establishment of the dependence of the wind-pump performance on the wind-pump's Froude number, υ/√ gh, an analytical analysis of the wind-pump's design parameters is further developed in this work. The result was the formulation of the system criteria that continuously match the load with the varying wind speed and water head. This led to a design procedure that entails variation of the pump stroke, the rotational speed-ratio or the turbine's pitch angle to sustain a continuous peak performance. The stroke and speed-ratio variations are such that any of them is continuously proportional to the square of the wind-pump's Froude number. The pitch-angle variation technique requires an inverse relation between the design torque-coefficient and the square of Froude number. The suggested power maximization techniques lead to the continuous operation of the turbine at its maximum power-coefficient point, as long as the operational Froude number is above its stop limit. The arrangements have the implicit advantage of minimizing the start and stop wind speeds of the wind pump.
Estimates of Insulin Secretory Function in Apparently Healthy Volunteers Vary as a Function of How the Relevant Variables Are Quantified
Authors: Johns Barry R , Abbasi Fahim , Reaven Gerald M 
Published: February 2011

BACKGROUND
Several surrogate estimates have been used to define relationships between insulin action and pancreatic β-cell function in healthy individuals. Because it is unclear how conclusions about insulin secretory function depend on specific estimates used, we evaluated the effect of different approaches to measurement of insulin action and secretion on observations of pancreatic β-cell function in individuals whose fasting plasma glucose (FPG) was &lt;7.0 mmol/L (126 mg/dL).

METHODS
We determined 2 indices of insulin secretion [homeostasis model assessment of β-cell function (HOMA-β) and daylong insulin response to mixed meals], insulin action [homeostasis model assessment of insulin resistance (HOMA-IR) and steady-state plasma glucose (SSPG) concentration during the insulin suppression test], and degree of glycemia [fasting plasma glucose (FPG) and daylong glucose response to mixed meals] in 285 individuals with FPG &lt;7.0 mmol/L. We compared the relationship between the 2 measures of insulin secretion as a function of the measures of insulin action and degree of glycemia.

RESULTS
Assessment of insulin secretion varied dramatically as a function of which of the 2 methods was used and which measure of insulin resistance or glycemia served as the independent variable. For example, the correlation between insulin secretion (HOMA-β) and insulin resistance varied from an r value of 0.74 (when HOMA-IR was used) to 0.22 (when SSPG concentration was used).

CONCLUSIONS
Conclusions about β-cell function in nondiabetic individuals depend on the measurements used to assess insulin action and insulin secretion. Viewing estimates of insulin secretion in relationship to measures of insulin resistance and/or degree of glycemia does not mean that an unequivocal measure of pancreatic β-cell function has been obtained.
Measurement of Hemoglobin A1c from Filter Papers for Population-Based Studies
Authors: Egier David A , Keys Judy L , Hall S Kim , McQueen Matthew J 
Published: February 2011

BACKGROUNDStability and transport challenges make hemoglobin (Hb) A1c measurement from EDTA whole blood (WB) inconvenient and costly for large-scale population studies. This study investigated Hb A1c measurement from WB blotted on filter paper (FP) in a Level I National Glycohemoglobin Standardization Program (NGSP)-accredited laboratory.METHODSThree Bio-Rad Variant™ II HPLC instruments and WB and FP specimens were used. Precision, accuracy, linearity, and readable total area of the 6.5-min (β-thalassemia method) Variant II HbA2/HbA1c Dual Program were assessed. Hb A1c stability was measured using in-house FP QC samples. The INTERHEART (a study of the effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries) and CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) studies provided chromatographs for morphometric analyses and interoperator variability experiments. Statistical analyses were performed to assess long-term sample stability, WB vs FP agreement, and significance of Hb A1c peak integration.RESULTSIntra- and interassay CVs were ≤2.00%. Total area counts between 0.8 and 5.5 × 106 μV/s produced accurate Hb A1c results. The regression equation for agreement between WB(x) and FP(y) was as follows: y = 0.933x + 0.4 (n = 85). FP QC samples stored at −70 °C and tested over approximately 3 years yielded CVs of 1.72%–2.73% and regression equations with slopes of −1.08 × 10−4 to 7.81 × 10−4. The CURE study, with better preanalytical preparation, achieved a 97% reportable rate, and the reportable rate of the INTERHEART study was 85%.CONCLUSIONSThe FP collection method described provided accurate, robust, and reproducible measurement of Hb A1c using the Bio-Rad Variant II HPLC autoanalyzer when FP specimens were prepared according to standardized protocols, and analyses were performed in an NGSP-certified laboratory, supporting the use of FP collection cards in large multinational studies.
Detection of Circulating Endothelial Cells via a Microfluidic Disk
Authors: Chen Ken-Chao , Lee Tai-Ping , Pan Yu-Cheng , Chiang Chi-Ling , Chen Chen-Lin , Yang Yao-Hsu , Chiang Bor-Luen , Lee Hsinyu , Wo Andrew M 
Published: February 2011

BACKGROUNDCirculating endothelial cells (CECs) in the blood are rare but have been shown to be associated with various diseases. With the ratio of CECs to peripheral blood mononuclear cells (PBMCs) less than 1 part per thousand, their separation from PBMCs and detection are challenging. We present a means of detecting CECs from PBMCs via an economical microfluidic disk with a model cell system [human umbilical vein endothelial cells (HUVECs) in PBMCs], along with demonstration of its efficacy clinically.METHODSTo enrich these rare cells, we used immunomagnetic beads and a tailor-made magnet on the disk. CEC-simulating HUVECs, as target cells, were stained with primary anti–CD146-phycoerythrin antibody and bound with secondary antibody on antiphycoerythrin magnetic beads. PBMCs served as nontarget cells and were labeled with anti–CD45-FITC antibody.RESULTSWhen hundreds of HUVECs were mixed in 106 PBMCs, 95% of spiked HUVECs were detected. This yield also held for 60 HUVEC in &lt;104 PBMCs. We compared data from flow cytometry with that from the disk: CEC counts in 50 μL blood from patients with systemic lupus erythematosus were 61.1 (21.5), significantly higher (P &lt; 0.01) than those of healthy donors, 31.2 (13.3).CONCLUSIONSThe count of CECs is a suitable marker for symptoms of systemic lupus erythematosus. The microfluidic disk system should be a viable platform for detection of CECs.
Clustered regularly interspaced short palindromic repeats (CRISPRs): the hallmark of an ingenious antiviral defense mechanism in prokaryotes
Authors: Al-Attar Sinan , Westra Edze R. , van der Oost John , Brouns Stan J.J. 
Published: February 2011

AbstractMany prokaryotes contain the recently discovered defense system against mobile genetic elements. This defense system contains a unique type of repetitive DNA stretches, termed Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs). CRISPRs consist of identical repeated DNA sequences (repeats), interspaced by highly variable sequences referred to as spacers. The spacers originate from either phages or plasmids and comprise the prokaryotes' ‘immunological memory’. CRISPR-associated (cas) genes encode conserved proteins that together with CRISPRs make-up the CRISPR/Cas system, responsible for defending the prokaryotic cell against invaders. CRISPR-mediated resistance has been proposed to involve three stages: (i) CRISPR-Adaptation, the invader DNA is encountered by the CRISPR/Cas machinery and an invader-derived short DNA fragment is incorporated in the CRISPR array. (ii) CRISPR-Expression, the CRISPR array is transcribed and the transcript is processed by Cas proteins. (iii) CRISPR-Interference, the invaders' nucleic acid is recognized by complementarity to the crRNA and neutralized. An application of the CRISPR/Cas system is the immunization of industry-relevant prokaryotes (or eukaryotes) against mobile-genetic invasion. In addition, the high variability of the CRISPR spacer content can be exploited for phylogenetic and evolutionary studies. Despite impressive progress during the last couple of years, the elucidation of several fundamental details will be a major challenge in future research.
Regulatory RNAs in cyanobacteria: developmental decisions, stress responses and a plethora of chromosomally encoded cis-antisense RNAs
Authors: Georg Jens , Hess Wolfgang R. 
Published: February 2011

Abstract
Cyanobacteria are the only prokaryotes which directly convert solar energy into biomass using oxygenic photosynthesis. Therefore, these bacteria are of interest for the production of biofuels, biotechnology and are of tremendous relevance for primary carbon fixation in many ecosystems. Mechanisms controlling gene expression cannot be understood entirely without information on the numbers and functions of regulatory RNAs. In cyanobacteria, non-coding RNAs have been characterized from simple unicellular species such as Prochlorococcus up to complex species such as Anabaena. Several of these RNAs function in the control of stress responses, photosynthesis, outer cell membrane protein biosynthesis and the differentiation of cells.
Thermal behaviour of Norway spruce and European beech in and between the principal anatomical directions
Authors: Sonderegger Walter , Hering Stefan , Niemz Peter 
Published: February 2011

Abstract
Thermal conductivity (ThCond), thermal diffusivity and heat capacity of Norway spruce (Picea abies [L.] Karst.) and European beech (Fagus sylvatica L.) have been determined for all principal directions – radial (R), tangential (T) and longitudinal (L) – depending on the moisture content (MC) and ThCond was additionally measured in 15° steps between these directions. The ThCond was determined in a guarded hot plate apparatus. For determining thermal diffusivity and heat capacity, the same apparatus was supplemented with thermocouples and the temperature evolution was evaluated numerically by a partial differential equation. The results show expectedly that ThCond increases with increasing MC, whereby the highest increment was observed in T and the lowest in L direction. ThCond is higher for beech than for spruce in all anatomical directions and the conductivity for both species is more than twice as high in L direction than perpendicular to grain. The highest ThCond is found for beech at a grain angle of approximately 15°. The lowest ThCond shows spruce at an angle of approximately 60° between T and R direction. Thermal diffusivity is similar for both species and decreases with increasing MC. Its differences with regard to the anatomical directions correlate with those of the ThCond values. Heat capacity is lower for beech than for spruce and shows a clear increase with increasing MC.
Highly stable acyclic bifunctional chelator for 64Cu PET imaging
Authors: Abada S. , Lecointre A. , Déchamps-Olivier I. , Platas-Iglesias C. , Christine C. , Elhabiri M. , Charbonniere L. 
Published: February 2011

Abstract
Ligand L1, based on a pyridine scaffold, functionalized by two bis(methane phosphonate)aminomethyl groups, was shown to display a very high affinity towards Cu(II) (log K
CuL=22.7) and selectivity over Ni(II), Co(II), Zn(II) and Ga(III) (Δ log K
ML>4) as shown by the values of the stability constants obtained from potentiometric measurements. Insights into the coordination mode of the ligand around Cu(II) cation were obtained by UV-Vis absorption and EPR spectroscopies as well as density functional theory (DFT) calculations (B3LYP model) performed in aqueous solution. The results point to a pentacoordination pattern of the metal ion in the fully deprotonated [CuL1]6− species. Considering the beneficial thermodynamic parameters of this ligand, kinetic experiments were run to follow the formation of the copper(II) complexes, indicating a very rapid formation of the complex, appropriat e for 64Cu complexation. As L1 represents a particularly interesting target within the frame of 64Cu PET imaging, a synthetic protocol was developed to introduce a labeling function on the pyridyl moiety of L1, thereby affording L2, a potential bifunctional chelator (BFC) for PET imaging.
Bioavailability of 99mTc-paclitaxel-glucuronide (99mTc-PAC-G)
Authors: Biber Muftuler Fazilet Zumrut , Demir Ilknur , Ünak P. , Ichedef Cigdem , Yurt Kilcar Ayfer 
Published: February 2011

Abstract
An antitumor agent paclitaxel (PAC) has been proved to be efficient in the treatment of breast and ovarian cancer. Glucuronic acid-derived paclitaxel compound [paclitaxel-glucuronide (PAC-G)] was enzymatically synthesized using microsome preparate separated from rat livers. The biodistribution mechanism of PAC-G in healthy female Albino Wistar rats has been investigated. The expected structure is confirmed according to LC/MS results, and the possible attachment is to C2-hydroxyl group. PAC-G was labeled with 99mTc and the radiochemical yield of radiolabeled compound (99mTc-PAC-G) was 98.0±02.74 (n=9). The range of the breast/blood and breast/muscle ratios is approximately between 3 and 35 in 240ߙmin. All these experimental studies indicate that 99mTc-PAC-G may potentially be used in breast tissue as an imaging agent.