bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered responsiveness to extracellular ATP enhances acetaminophen hepatotoxicity
Authors: Amaral Sylvia S , Oliveira André G , Marques Pedro E , Quintão Jayane L D , Pires Daniele A , Resende Rodrigo R , Sousa Bruna R , Melgaço Juliana G , Pinto Marcelo A , Russo Remo C , Gomes Ariane k C , Andrade Lidia M , Zanin Rafael F , Pereira Rafaela V S , Bonorino Cristina , Soriani Frederico M , Lima Cristiano X , Cara Denise C , Teixeira Mauro M , Leite Maria F , Menezes Gustavo B 
Published: February 2013

Abstract

Background
Adenosine triphosphate (ATP) is secreted from hepatocytes under physiological conditions and plays an important role in liver biology through the activation of P2 receptors. Conversely, higher extracellular ATP concentrations, as observed during necrosis, trigger inflammatory responses that contribute to the progression of liver injury. Impaired calcium (Ca2+) homeostasis is a hallmark of acetaminophen (APAP)-induced hepatotoxicity, and since ATP induces mobilization of the intracellular Ca2+ stocks, we evaluated if the release of ATP during APAP-induced necrosis could directly contribute to hepatocyte death.

Results
APAP overdose resulted in liver necrosis, massive neutrophil infiltration and large non-perfused areas, as well as remote lung inflammation. In the liver, these effects were significantly abrogated after ATP metabolism by apyrase or P2X receptors blockage, but none of the treatments prevented remote lung inflammation, suggesting a confined local contribution of purinergic signaling into liver environment. In vitro, APAP administration to primary mouse hepatocytes and also HepG2 cells caused cell death in a dose-dependent manner. Interestingly, exposure of HepG2 cells to APAP elicited significant release of ATP to the supernatant in levels that were high enough to promote direct cytotoxicity to healthy primary hepatocytes or HepG2 cells. In agreement to our in vivo results, apyrase treatment or blockage of P2 receptors reduced APAP cytotoxicity. Likewise, ATP exposure caused significant higher intracellular Ca2+ signal in APAP-treated primary hepatocytes, which was reproduced in HepG2 cells. Quantitative real time PCR showed that APAP-challenged HepG2 cells expressed higher levels of several purinergic receptors, which may explain the hypersensitivity to extracellular ATP. This phenotype was confirmed in humans analyzing liver biopsies from patients diagnosed with acute hepatic failure.

Conclusion
We suggest that under pathological conditions, ATP may act not only an immune system activator, but also as a paracrine direct cytotoxic DAMP through the dysregulation of Ca2+ homeostasis.
Protocol: optimising hydroponic growth systems for nutritional and physiological analysis of Arabidopsis thaliana and other plants
Authors: Conn Simon J , Hocking Bradleigh , Dayod Maclin , Xu Bo , Athman Asmini , Henderson Sam , Aukett Lucy , Conn Vanessa , Shearer Monique K , Fuentes Sigfredo , Tyerman Stephen D , Gilliham Matthew 
Published: February 2013

Abstract

Background
Hydroponic growth systems are a convenient platform for studying whole plant physiology. However, we found through trialling systems as they are described in the literature that our experiments were frequently confounded by factors that affected plant growth, including algal contamination and hypoxia. We also found the way in which the plants were grown made them poorly amenable to a number of common physiological assays.

Results
The drivers for the development of this hydroponic system were: 1) the exclusion of light from the growth solution; 2) to simplify the handling of individual plants, and 3) the growth of the plant to allow easy implementation of multiple assays. These aims were all met by the use of pierced lids of black microcentrifuge tubes. Seed was germinated on a lid filled with an agar-containing germination media immersed in the same solution. Following germination, the liquid growth media was exchanged with the experimental solution, and after 14-21 days seedlings were transferred to larger tanks with aerated solution where they remained until experimentation. We provide details of the protocol including composition of the basal growth solution, and separate solutions with altered calcium, magnesium, potassium or sodium supply whilst maintaining the activity of the majority of other ions. We demonstrate the adaptability of this system for: gas exchange measurement on single leaves and whole plants; qRT-PCR to probe the transcriptional response of roots or shoots to altered nutrient composition in the growth solution (we demonstrate this using high and low calcium supply); producing highly competent mesophyll protoplasts; and, accelerating the screening of Arabidopsis transformants. This system is also ideal for manipulating plants for micropipette techniques such as electrophysiology or SiCSA.

Conclusions
We present an optimised plant hydroponic culture system that can be quickly and cheaply constructed, and produces plants with similar growth kinetics to soil-grown plants, but with the advantage of being a versatile platform for a myriad of physiological and molecular biological measurements on all plant tissues at all developmental stages. We present ‘tips and tricks’ for the easy adoption of this hydroponic culture system.
Comparison of the dipeptidyl peptidase-4 gene methylation levels between severely obese subjects with and without the metabolic syndrome
Authors: Turcot Valérie , Tchernof André , Deshaies Yves , Pérusse Louis , Bélisle Alexandre , Marceau Picard , Hould Frédéric-Simon , Lebel Stéfane , Vohl Marie-Claude 
Published: February 2013

Abstract

Background
The dipeptidyl peptidase-4 (DPP4) enzyme is a novel adipokine potentially involved in the development of the metabolic syndrome (MetS). Previous observations demonstrated higher visceral adipose tissue (VAT) DPP4 gene expression in non-diabetic severely obese men with (MetS+) vs. without (MetS−) MetS. DPP4 mRNA abundance in VAT correlated also with CpG site methylation levels (%Meth) localized within and near its exon 2 (CpG94 to CpG102) in non-diabetic severely obese women, regardless of their MetS status. The actual study tested whether DPP4 %Meth levels in VAT are different between MetS− and MetS+ non-diabetic severely obese subjects, whether variable metabolic and plasma lipid profiles are observed between DPP4 %Meth quartiles, and whether correlation exists in DPP4 %Meth levels between VAT and white blood cells (WBCs).

Methods
DNA was extracted from the VAT of 26 men (MetS−: n=12, MetS+: n=14) and 79 women (MetS−: n=60; MetS+: n=19), as well as from WBCs in a sub-sample of 17 women (MetS−: n=9; MetS+: n=8). The %Meth levels of CpG94 to CpG102 were assessed by pyrosequencing of sodium bisulfite-treated DNA. ANOVA analyses were used to compare the %Meth of CpGs between MetS− and MetS+ groups, and to compare the metabolic phenotype and plasma lipid levels between methylation quartiles. Pearson correlation coefficient analyses were computed to test the relationship between VAT and WBCs CpG94-102 %Meth levels.

Results
No difference was observed in CpG94-102 %Meth levels between MetS− and MetS+ subjects in VAT (P=0.67), but individuals categorized into CpG94-102 %Meth quartiles had variable plasma total-cholesterol concentrations (P=0.04). The %Meth levels of four CpGs in VAT were significantly correlated with those observed in WBCs (r=0.55−0.59, P≤0.03).

Conclusions
This study demonstrated that %Meth of CpGs localized within and near the exon 2 of the DPP4 gene in VAT are not associated with MetS status. The actual study also revealed an association between the %Meth of this locus with plasma total-cholesterol in severe obesity, which suggests a link between the DPP4 gene and plasma lipid levels.
Expiratory time constant for determinations of plateau pressure, respiratory system compliance, and total resistance
Authors: Al-Rawas Nawar , Banner Michael J , Euliano Neil R , Tams Carl G , Brown Jeff , Martin A Daniel , Gabrielli Andrea 
Published: February 2013

Abstract
Introduction
We hypothesized the expiratory time constant (ƬE) may be used to provide real time determinations of inspiratory plateau pressure (Pplt), respiratory system compliance (Crs), and total resistance (respiratory system resistance plus series resistance of endotracheal tube) (Rtot) of patients with respiratory failure using various modes of ventilatory support.

Methods
Adults (n = 92) with acute respiratory failure were categorized into four groups depending on the mode of ventilatory support ordered by attending physicians, i.e., volume controlled-continuous mandatory ventilation (VC-CMV), volume controlled-synchronized intermittent mandatory ventilation (VC-SIMV), volume control plus (VC+), and pressure support ventilation (PSV). Positive end expiratory pressure as ordered was combined with all aforementioned modes. Pplt, determined by the traditional end inspiratory pause (EIP) method, was combined in equations to determine Crs and Rtot. Following that, the ƬE method was employed, ƬE was estimated from point-by-point measurements of exhaled tidal volume and flow rate, it was then combined in equations to determine Pplt, Crs, and Rtot. Both methods were compared using regression analysis.

Results
ƬE, ranging from mean values of 0.54 sec to 0.66 sec, was not significantly different among ventilatory modes. The ƬE method was an excellent predictor of Pplt, Crs, and Rtot for various ventilatory modes; r2 values for the relationships of ƬE and EIP methods ranged from 0.94 to 0.99 for Pplt, 0.90 to 0.99 for Crs, and 0.88 to 0.94 for Rtot (P <0.001). Bias and precision values were negligible.

Conclusions
We found the ƬE method was just as good as the EIP method for determining Pplt, Crs, and Rtot for various modes of ventilatory support for patients with acute respiratory failure. It is unclear if the ƬE method can be generalized to patients with chronic obstructive lung disease. ƬE is determined during passive deflation of the lungs without the need for changing the ventilatory mode and disrupting a patient's breathing. The ƬE method obviates the need to apply an EIP, allows for continuous and automatic surveillance of inspiratory Pplt so it can be maintained ≤ 30 cm H2O for lung protection and patient safety, and permits real time assessments of pulmonary mechanics.
Evaluation of early mini-bronchoalveolar lavage in the diagnosis of health care-associated pneumonia: a prospective study
Authors: Lacroix Guillaume , Prunet Bertrand , Bordes Julien , Cabon-Asencio Nathalie , Asencio Yves , Gaillard Tiphaine , Pons Sandrine , D'aranda Erwan , Kerebel Delphine , Meaudre Eric , Goutorbe Philippe 
Published: February 2013

Abstract
Introduction
Health care-associated pneumonia (HCAP) has been proposed as a new category of respiratory infection to identify patients at risk of multidrug-resistant (MDR) pathogens. The American Thoracic Society's recommendation for HCAP treatment is to use broad-spectrum and multiple antibiotics. However, this strategy may be economically expensive and promote antimicrobial resistance when a multisensitive pathogen is not identified.

Methods
We prospectively included all patients presenting with HCAP in the emergency department. Blood cultures and fiberoptic bronchoscope-guided distal protected small volume bronchoalveolar lavage (FODP mini-BAL) were performed in each patient. Empirical antibiotic therapy was adapted when microbiological findings were available. The primary objective was to assess whether FODP mini-BAL is more efficient than blood cultures in identifying pathogens with the ratio of identification between both techniques as principal criteria.

Results
We included 54 patients with HCAP. Pathogens were identified in 46.3% of cases using mini-BAL and in 11.1% of cases using blood cultures (P <0.01). When the patient did not receive antibiotic therapy before the procedure, pathogens were identified in 72.6% of cases using mini-BAL and in 9.5% of cases using blood cultures (P <0.01). We noted multidrug-resistant pathogens in 16% of cases. All bronchoscopic procedures could be performed in patients without complications.

Conclusions
FODP mini-BAL was more efficient than blood cultures for identifying pathogens in patients presenting with HCAP. When bacteriological identification was obtained, antibiotic therapy was adapted in 100% of cases.
See related letter by Sircar et al.,http://ccforum.com/content/17/2/428
Female Reproductive Health After Childhood, Adolescent, and Young Adult Cancers: Guidelines for the Assessment and Management of Female Reproductive Complications
Authors: Metzger Monika L. , Meacham Lillian R. , Patterson Briana , Casillas Jacqueline S. , Constine Louis S. , Hijiya Nobuko , Kenney Lisa B. , Leonard Marcia , Lockart Barbara A. , Likes Wendy , Green Daniel M. 
Published: February 2013

PurposeAs more young female patients with cancer survive their primary disease, concerns about reproductive health related to primary therapy gain relevance. Cancer therapy can often affect reproductive organs, leading to impaired pubertal development, hormonal regulation, fertility, and sexual function, affecting quality of life.MethodsThe Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer (COG-LTFU Guidelines) are evidence-based recommendations for screening and management of late effects of therapeutic exposures. The guidelines are updated every 2 years by a multidisciplinary panel based on current literature review and expert consensus.ResultsThis review summarizes the current task force recommendations for the assessment and management of female reproductive complications after treatment for childhood, adolescent, and young adult cancers. Experimental pretreatment as well as post-treatment fertility preservation strategies, including barriers and ethical considerations, which are not included in the COG-LTFU Guidelines, are also discussed.ConclusionOngoing research will continue to inform COG-LTFU Guideline recommendations for follow-up care of female survivors of childhood cancer to improve their health and quality of life.
Nerve growth factor reduces myocardial ischemia/reperfusion injury in rat hearts
Authors: Strande Jennifer L. , Routhu Kasi V. , Lecht Shimon , Lazarovici Philip 
Published: February 2013

Abstract

Background: Nerve growth factor (NGF) is a neurotrophin that supports the survival and differentiation of sympathetic neurons, and its increased expression after myocardial infarct was correlated with cardiac sympathetic hyperinnervation and arrhythmias. However, it is unclear whether NGF protects the heart during infarct. In this study, we sought to address this issue in rat heart exposed to ischemia/reperfusion injury (IRI).

Methods: NGF was administered intravenously (IV), 15 min before ischemia, at different concentrations in the absence or presence of inhibitors of phosphatidylinositol-3 kinase (PI3K) or nitric oxide synthase (NOS) in different groups of rats (n=6) with left coronary occlusion for 30 min followed by 120-min reperfusion. The area at risk and infarct to risk ratios were determined from sections stained with 1% 2,3,5-triphenylterazolium chloride.

Results: NGF treatment at doses of 0.015–15 μg/kg, with an optimal dose of 0.15 μg/kg given IV before ischemia, reduced the infarct size from about 60% at the area of risk to about 25%, indicating cardioprotection by about 60%. The infarct-sparing effects of NGF were partially abolished by the inhibition of PI3K and NOS using wortmannin and N(G)-monomethyl-l-arginine, respectively.

Conclusions: We have demonstrated for the first time that NGF attenuates myocardial infarct damage in an in vivo rat model of myocardial regional IRI. This cardioprotective effect is proposed to be related to the activities of PI3K and NOS. This suggests that NGF has a potential therapeutic role in the treatment of IRI.
Rate- and Temperature-Dependent Fracture Characteristics of Asphaltic Paving Mixtures
Authors: Im Soohyok , Kim Yong-Rak , Ban Hoki 
Published: February 2013

Abstract
Cracking in asphaltic pavement layers causes primary failure of the roadway structure, and the fracture resistance and characteristics of asphalt mixtures significantly influence the service life of asphaltic roadways. A better understanding of the fracture process is considered a necessary step to the proper development of design-analysis procedures for asphaltic mixtures and pavement structures. However, such effort involves many challenges because of the complex nature of asphaltic materials. In this study, experiments were conducted using uniaxial compressive specimens to characterize the linear viscoelastic properties and semi-circular bending (SCB) specimens to characterize fracture behavior of a typical dense-graded asphalt paving mixture subjected to various loading rates and at different temperatures. The SCB fracture test was also incorporated with a digital image correlation (DIC) system and finite-element model simulations including material viscoelasticity and cohesive-zone fracture to effectively capture local fracture processes and resulting fracture properties. The test results and model simulations clearly demonstrate that: (1) the rate- and temperature-dependent fracture characteristics need to be identified at the local fracture process zone, and (2) the rate- and temperature-dependent fracture properties are necessary in the structural design of asphaltic pavements with which a wide range of strain rates and service temperatures is usually associated.
Practical electrical contact resistance measurement method for bulk thermoelectric devices
Authors: Gupta Rahul P. , McCarty Robin , Bierschenk Jim , Sharp Jeff 
Published: February 2013

ABSTRACTAs thermoelectric (TE) element length decreases, the impact of contact resistance on TE device performance grows more significant. In fact, for a TE device containing 100-μm tall Bi2Te3TE elements, the figure of merit ratio (ZTDevice/ZTMaterial) drops from 0.9 to 0.5 as the contact resistivity increases from 5 x 10-07 to 5 x 10-06 Ω-cm2. To understand the effects of contact resistance on bulk TE device performance, a reliable experimental measurement method is needed. There are many popular methods to extract contact resistance such as Transmission Line Measurements (TLM) and Kelvin Cross Bridge Resistor method (KCBR), but they are only well-suited for measuring metal contacts on thin films and do not necessarily translate to measuring contact resistance on bulk thermoelectric materials. The authors present a new measurement technique that precisely measures contact resistance (on the order of 5 x 10-07 Ω-cm2) on bulk thermoelectric materials by processing stacks of bulk, metal-coated TE wafers using TE industry standard processes. One advantage of this technique is that it exploits realistic TE device manufacturing techniques and results in an almost device-like structure, therefore representing a realistic value for electrical contact resistance in a bulk TE device. Contact resistance measurements for metal contacts to n- and p-type Bi2Te3 alloys are presented and an estimate of the accuracy of the measurements is discussed.
Enhancement in Thermoelectric Figure-of-merit of n-type Si-Ge Alloy Synthesized Employing High Energy Ball Milling and Spark Plasma Sintering
Authors: Bathula Sivaiah , Jayasimhadri M. , Dhar Ajay , Saravanan M. , Misra D. K. , Singh Nidhi , Srivastava A. K. , Budhani R. C. 
Published: February 2013

ABSTRACTIn the present study, we report the enhancement in figure-of-merit (ZT) of nanostructured n-type Silicon-Germanium (Si80Ge20) thermoelectric alloy synthesized using high energy ball milling followed by spark plasma sintering (SPS). After 90 h of ball milling of elemental powders of Si, Ge and P (2 at.%), a complete dissolution of Ge in Si matrix has been observed forming the nanostructured n-type Si80Ge20 alloy powder. X-ray diffraction analysis (XRD) confirmed the crystallite size of the host matrix (Si) to be ∼7 nm and also indicated the formation of an additional phase of SiP nano-precipitates after SPS. HR-TEM analysis revealed that the nano-grained network was retained post-sintering with a crystallite size of size of 9 nm and also confirmed the SiP precipitates formation with a size of 4 to 6 nm. As a result, a very low thermal conductivity of ∼2.3W/mK at 900°C has been observed for Si80Ge20 alloy primarily due to scattering of phonons by nanostructured grains and nano-scaled SiP precipitates which further contribute to this scattering mechanism. Electrical conductivity values of SiGe sintered alloy are slightly lower to that of reported values in literature. This was attributed to the formation of SiP which creates a compositional difference between the grain boundary region and the grain region, leading to a chemical potential difference at interface and the grain region. Figure-of-merit (ZT) of n-type Si80Ge20 nanostructured alloy was found to be ≈1.5 at 900°C, which is the highest reported so far at this temperature.
Coupling In-Situ Techniques to Analyze Zinc Deposition and Dissolution for Energy Storage Applications
Authors: Keist Jayme , Orme Christine , Ross Frances , Steingart Dan , Wright Paul , Evans James 
Published: February 2013

ABSTRACTThis investigation describes preliminary results of in-situ analysis of zinc deposition within an ionic liquid electrolyte utilizing electrochemical atomic force microscopy (EC AFM). From the AFM analysis, the morphology of the zinc deposition was analyzed by quantifying the surface roughness using height-height correlation functions. These results will be used to analyze the scattering data obtained from zinc deposition analysis utilizing an electrochemical ultra-small angle x-ray scattering (EC USAXS). The goal of this research is to link the early nucleation and growth behavior to the formation of detrimental morphologies.
Inkjetted Organic Transistors using a Novel Pentacene Precursor
Authors: Volkman Steven K. , Molesa Steven , Mattis Brian , Chang Paul C. , Subramanian Vivek 
Published: February 2013

AbstractPentacene is one of the most promising organic materials for organic transistor fabrication, since it offers higher mobility, better on-off ratio, improved environmental stability, and better reliability than most other organic semiconductors. However, its severe insolubility renders it useless for the solution-based fabrication of electronic devices. Solution-based processing is the key to enabling ultra-low-cost circuit fabrication, since it eliminates the need for lithography, subtractive processing, and vacuum-based film deposition. Using a recently developed soluble pentacene precursor, we demonstrate the first inkjet-printed pentacene transistor fabricated to date. This is achieved using a substrate-gated transistor structure in conjunction with an inkjetprinted pentacene precursor active layer. After deposition, the precursor is converted to pentacene via heating, through the decomposition of the Diels-Alder product. As the anneal temperature increases above 120°C, performance increases dramatically. The process is therefore compatible with numerous low-temperature plastics. As the anneal time is increased to several minutes, performance likewise increases through increased precursor decomposition. However, exposure to excess temperatures or times tends to degrade performance. This is caused by morphological and chemical changes in the pentacene film. Optimization of the anneal process alone has resulted in the demonstration of transistors with an on-off ratio of >105 and field-effect mobility of >0.01cm2/V-s, attesting to the great promise of this material.