bluuebunny/crossref_metadata_2025 huggingface dataset:
Anacardic Acid, Salicylic Acid, and Oleic Acid Differentially Alter Cellular Bioenergetic Function in Breast Cancer Cells
Authors: Radde Brandie N. , Alizadeh‐Rad Negin , Price Stephanie M. , Schultz David J. , Klinge Carolyn M.
Published: March 2016

Anacardic acid is a dietary and medicinal phytochemical that inhibits breast cancer cell proliferation and uncouples oxidative phosphorylation (OXPHOS) in isolated rat liver mitochondria. Since mitochondrial‐targeted anticancer therapy (mitocans) may be useful in breast cancer, we examined the effect of anacardic acid on cellular bioenergetics and OXPHOS pathway proteins in breast cancer cells modeling progression to endocrine‐independence: MCF‐7 estrogen receptor α (ERα)+ endocrine‐sensitive; LCC9 and LY2 ERα+, endocrine‐resistant, and MDA‐MB‐231 triple negative breast cancer (TNBC) cells. At concentrations similar to cell proliferation IC50s, anacardic acid reduced ATP‐linked oxygen consumption rate (OCR), mitochondrial reserve capacity, and coupling efficiency while increasing proton leak, reflecting mitochondrial toxicity which was greater in MCF‐7 compared to endocrine‐resistant and TNBC cells. These results suggest tolerance in endocrine‐resistant and TNBC cells to mitochondrial stress induced by anacardic acid. Since anacardic acid is an alkylated 2‐hydroxybenzoic acid, the effects of salicylic acid (SA, 2‐hydroxybenzoic acid moiety) and oleic acid (OA, monounsaturated alkyl moiety) were tested. SA inhibited whereas OA stimulated cell viability. In contrast to stimulation of basal OCR by anacardic acid (uncoupling effect), neither SA nor OA altered basal OCR‐ except OA inhibited basal and ATP‐linked OCR, and increased ECAR, in MDA‐MB‐231 cells. Changes in OXPHOS proteins correlated with changes in OCR. Overall, neither the 2‐hydroxybenzoic acid moiety nor the monounsaturated alky moiety of anacardic acid is solely responsible for the observed mitochondria‐targeted anticancer activity in breast cancer cells and hence both moieties are required in the same molecule for the observed effects. J. Cell. Biochem. 117: 2521–2532, 2016. © 2016 Wiley Periodicals, Inc.
l‐glutamine Improves Skeletal Muscle Cell Differentiation and Prevents Myotube Atrophy After Cytokine (TNF‐α) Stress Via Reduced p38 MAPK Signal Transduction
Authors: Girven Matthew , Dugdale Hannah F. , Owens Daniel J. , Hughes David C. , Stewart Claire E. , Sharples Adam P.
Published: March 2016

Tumour Necrosis Factor‐Alpha (TNF‐α) is chronically elevated in conditions where skeletal muscle loss occurs. As l‐glutamine can dampen the effects of inflamed environments, we investigated the role of l‐glutamine in both differentiating C2C12 myoblasts and existing myotubes in the absence/presence of TNF‐α (20 ng · ml−1) ± l‐glutamine (20 mM). TNF‐α reduced the proportion of cells in G1 phase, as well as biochemical (CK activity) and morphological differentiation (myotube number), with corresponding reductions in transcript expression of: Myogenin, Igf‐I, and Igfbp5. Furthermore, when administered to mature myotubes, TNF‐α induced myotube loss and atrophy underpinned by reductions in Myogenin, Igf‐I, Igfbp2, and glutamine synthetase and parallel increases in Fox03, Cfos, p53, and Bid gene expression. Investigation of signaling activity suggested that Akt and ERK1/2 were unchanged, JNK increased (non‐significantly) whereas P38 MAPK substantially and significantly increased in both myoblasts and myotubes in the presence of TNF‐α. Importantly, 20 mM l‐glutamine reduced p38 MAPK activity in TNF‐α conditions back to control levels, with a corresponding rescue of myoblast differentiation and a reversal of atrophy in myotubes. l‐glutamine resulted in upregulation of genes associated with growth and survival including; Myogenin, Igf‐Ir, Myhc2 & 7, Tnfsfr1b, Adra1d, and restored atrophic gene expression of Fox03 back to baseline in TNF‐α conditions. In conclusion, l‐glutamine supplementation rescued suppressed muscle cell differentiation and prevented myotube atrophy in an inflamed environment via regulation of p38 MAPK. l‐glutamine administration could represent an important therapeutic strategy for reducing muscle loss in catabolic diseases and inflamed ageing. J. Cell. Physiol. 9999: 231: 2720–2732, 2016. © 2016 Wiley Periodicals, Inc.
TNF‐α Induces Caspase‐1 Activation Independently of Simultaneously Induced NLRP3 in 3T3‐L1 Cells
Authors: Furuoka Mana , Ozaki Kei‐Ichi , Sadatomi Daichi , Mamiya Sayaka , Yonezawa Tomo , Tanimura Susumu , Takeda Kohsuke
Published: March 2016

The intracellular cysteine protease caspase‐1 is critically involved in obesity‐induced inflammation in adipose tissue. A substantial body of evidence from immune cells, such as macrophages, has shown that caspase‐1 activation depends largely on a protein complex, called the NLRP3 inflammasome, which consists of the NOD‐like receptor (NLR) family protein NLRP3, the adaptor protein ASC, and caspase‐1 itself. However, it is not fully understood how caspase‐1 activation is regulated within adipocytes upon inflammatory stimuli. In this study, we show that TNF‐α‐induced activation of caspase‐1 is accompanied by robust induction of NLRP3 in 3T3‐L1 adipocytes but that caspase‐1 activation may not depend on the NLRP3 inflammasome. Treatment of 3T3‐L1 cells with TNF‐α induced mRNA expression and activation of caspase‐1. Although the basal expression of NLRP3 and ASC was undetectable in unstimulated cells, TNF‐α strongly induced NLRP3 expression but did not induce ASC expression. Interestingly, inhibitors of the ERK MAP kinase pathway strongly suppressed NLRP3 expression but did not suppress the expression and activation of caspase‐1 induced by TNF‐α, suggesting that NLRP3 is dispensable for TNF‐α‐induced caspase‐1 activation. Moreover, we did not detect the basal and TNF‐α‐induced expression of other NLR proteins (NLRP1a, NLRP1b, and NLRC4), which do not necessarily require ASC for caspase‐1 activation. These results suggest that TNF‐α induces caspase‐1 activation in an inflammasome‐independent manner in 3T3‐L1 cells and that the ERK‐dependent expression of NLRP3 may play a role independently of its canonical role as a component of inflammasomes. J. Cell. Physiol. 231: 2761–2767, 2016. © 2016 Wiley Periodicals, Inc.
Potential Underprediction of Warfarin Drug Interaction From Conventional Interaction Studies and Risk Mitigation: A Case Study With Epacadostat, an IDO1 Inhibitor
Authors: Shi Jack G. , Chen Xuejun , Punwani Naresh G. , Williams William V. , Yeleswaram Swamy
Published: March 2016

Drug–drug interaction (DDI) studies involving warfarin are typically conducted with subtherapeutic doses of warfarin to ensure the safety of volunteers. However, this approach may potentially have a systemic bias of underestimating pharmacodynamic (PD) DDI effect on warfarin at therapeutic levels of anticoagulation. We demonstrate here the utility of model‐based DDI prediction for a clinically relevant warfarin regimen, using the example of epacadostat (INCB024360), the first‐in‐class indoleamine 2,3‐dioxygenase 1 inhibitor in clinical development as a novel orally active immuno‐oncological therapy. Observed data from a dedicated clinical DDI study using subtherapeutic warfarin suggested warfarin pharmacokinetics (PK), but not PD (anticoagulation), was significantly affected by concomitant epacadostat. However, subsequent PK/PD modeling and simulations indicated a clinically important DDI effect on warfarin PD at a higher baseline of the international normalization ratio (INR) and enabled recommendation of warfarin dose adjustment that is dependent on epacadostat dosing regimen and target INR.
Triphenylphosphine (PPh3) Catalyzed Erlenmeyer Reaction for Azlactones under Solvent‐free Conditions
Authors: Punna Rao Alapati Mohan Lakshmi , Sridhar Rao Abburi , Saratchandra Babu Mukkamala , Krishnaji Rao M.
Published: March 2016

This study presents triphenylphosphine catalyzed process for the synthesis of azlactones and their derivatives using hippuric and substituted aromatic aldehydes. The methodology also found to be effective for the synthesis of azlactones from 5‐(2,6‐dichlorophenyl)‐3‐methyl‐1,2‐oxazol‐4‐yl carbonyl amino acetic acid and offers several advantages such as solvent‐free conditions, excellent yields, simple procedure, mild conditions, and reduced environmental consequences.
Characterization of dengue virus infections in a sample of patients suggests unique clinical, immunological, and virological profiles that impact on the diagnosis of dengue and dengue hemorrhagic fever
Authors: Senaratne Thamarasi , Wimalaratne Harith , Alahakoon D. G. S. , Gunawardane Nirmali , Carr Jillian , Noordeen Faseeha
Published: March 2016

Dengue virus (DENV) infections are increasing with respect to incidence and severity in the Central Province of Sri Lanka. The objective of this study was to define the clinical, immunological, and virological profiles of patients admitted to the General Hospital, Kandy with clinically apparent dengue. Demographic, clinical, hematological parameters, liver enzymes (ALT and AST), and blood samples were collected from 292 patients with fever <5 days post onset and fulfilling the WHO criteria for the diagnosis of dengue fever/dengue hemorrhagic fever (DF/DHF). Samples were analyzed for, anti‐DENV IgM, IgG, and DENV nucleic acid. Myalgia was the commonest complaint by 65% of the patients. Packed cell volume was >45% in 27% of the patients while 42.12% had reduced platelets and 62.67% had reduced white blood cell counts. In contrast to other studies, positive tourniquet test (PTT) and petechiae were not major indicators of DENV infection or severity of the disease. Clinical profiles were significantly different between DF and DHF/DSS and showed many similarities to that reported elsewhere. Altogether, 43 patients (14.73%) were viremic as detected by RT‐PCR; 181 patients (62%) were positive for anti‐DENV IgM, and 245 (84%) patients were positive for anti‐DENV IgG. In combination, anti‐DENV IgM and RT‐PCR assays detected 224 (77.5%) of DENV infected cases, thus improving the DENV diagnosis rate. Hence, the diagnostic utility of PTT, anti‐DENV IgM/IgG serology, or RT‐PCR used alone in the early phase of illness is low in Sri Lanka but the diagnostic value can be improved by a combination of serology and RT‐PCR. J. Med. Virol. 88:1703–1710, 2016. © 2016 Wiley Periodicals, Inc.
Clinical impact of the hepatitis C virus mutations in the era of directly acting antivirals
Authors: Coppola Nicola , Minichini Carmine , Starace Mario , Sagnelli Caterina , Sagnelli Evangelista
Published: March 2016

Introduced in 2013–2014, the second‐ and third‐wave directly acting antivirals (DAAs) have strongly enhanced the efficacy and tolerability of anti‐HCV treatment, with a sustained virological response (SVR) in 90–95% of cases treated. The majority of patients who did not achieve an SVR were found to be infected with HCV strains with a reduced susceptibility to these drugs. Indeed, the high error rate of the viral polymerase and a fast virion production (100‐fold higher than the human immunodeficiency virus) result in a mixture of viral genetic populations (quasi‐species) pre‐existing treatment initiation. These mutants occur frequently in the NS5A region, with a moderate frequency in the NS3/4A region and rarely in the NS5B region. Treatment‐induced resistant mutants to NS5A DAAs persist for years after treatment discontinuation, whereas those resistant to the NS3 DAAs have a shorter duration. This review focuses on the type and prevalence of viral strains with a reduced sensitivity to DAAs, their clinical impact and influence on the response to treatment and, consequently, on treatment choice for DAA‐experienced patients. J. Med. Virol. 88:1659–1671, 2016. © 2016 Wiley Periodicals, Inc.
Changing pattern of dengue virus serotypes circulating during 2008–2012 and reappearance of dengue serotype 3 may cause outbreak in Kolkata, India
Authors: Saha Kallol , Ghosh Monika , Firdaus Rushna , Biswas Aritra , Seth Bikash , Bhattacharya Debojyoti , Mukherjee Kheya , Sadhukhan Provash Chandra
Published: March 2016

Dengue virus infection is a major cause of morbidity within the endemic tropical and subtropical regions of the world. Dengue virus has four distinct serotypes with specific clinical manifestations. In this study, we observed the changing pattern of dengue serotypes, age‐wise dengue infection and useful sero‐detection methods needed in a dengue endemic region. We identified dengue serotypes during a period of 5 years among patients with dengue symptoms visiting one of the largest tertiary care infectious disease hospitals of eastern India in Kolkata. A total of 433 dengue RNA positive samples were isolated from 712 acute dengue suspected cases. Age wise distribution highlighted the susceptible age group being >21 years (24.02%) followed by 11–15 years (21.71%) and 5–10 years (21.02%) of the total infected population. Higher numbers of infected cases were found within females as they are involved in more indoor works. The period of study experienced two dengue outbreaks one in 2008 and another in 2012. For early dengue detection, NS1 was found to be more confirmatory than IgM ELISA regarding sensitivity and specificity. DENV‐1, 2, and 4 serotypes were the common circulating strains from 2008 until 2010, after which DENV‐3 serotype infections rise and led to a massive dengue outbreak in Kolkata with increased numbers of DHF and DSS cases in 2012. The finding within our study emphasizes the public health importance of such prospective surveillance programs with respect to the changing dengue viral etiology and serotypes. J. Med. Virol. 88:1697–1702, 2016. © 2016 Wiley Periodicals, Inc.
Effects of motion segment level, Pfirrmann intervertebral disc degeneration grade and gender on lumbar spine kinematics
Authors: Muriuki Muturi G. , Havey Robert M. , Voronov Leonard I. , Carandang Gerard , Zindrick Michael R. , Lorenz Mark A. , Lomasney Laurie , Patwardhan Avinash G.
Published: March 2016

MRI allows non‐invasive assessment of intervertebral disc degeneration with the added clinical benefit of using non‐ionizing radiation. What has remained unclear is the relationship between assessed disc degeneration and lumbar spine kinematics. Kinematic outcomes of 54 multi‐segment (L1‐Sacrum) lumbar spine specimens were calculated to discover if such an underlying relationship exists with degeneration assessed using the Pfirrmann grading system. Further analyses were also conducted to determine if kinematic outcomes were affected by motion segment level, gender or applied compressive preload. Range of motion, hysteresis, high flexibility zone size and rotational stiffness in flexion‐extension, lateral bending and axial rotation were the kinematic outcomes. Caudal intervertebral discs in our study sample were more degenerative than cranial discs. L5‐S1 discs had the largest flexion‐extension range of motion (p < 0.005) and L1‐L2 discs the lowest flexion high flexibility zone size (p < 0.013). No other strict cranial‐caudal differences in kinematic outcomes were found. Low flexibility zone rotational stiffness increased with disc degeneration grade in extension, lateral bending and axial rotation (p < 0.001). Trends towards higher hysteresis and lower range of motion with increased degeneration were observed in flexion‐extension and lateral bending. Applied compressive preload increased flexion‐extension hysteresis and augmented the effect of degeneration on hysteresis (p < 0.0005). Female specimens had about one degree larger range of motion in all rotational modes, and higher flexion extension hysteresis (p = 0.016). These results suggest that gender differences exist in lumbar spine kinematics. Additionally high disc loads, applied compressive preload or applied moment, are needed to kinematically distinguish discs with different levels of degeneration. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1389–1398, 2016.
BMPR1A antagonist differentially affects cartilage and bone formation during fracture healing
Authors: Morgan Elise F. , Pittman Jason , DeGiacomo Anthony , Cusher Daniel , de Bakker Chantal M. J. , Mroszczyk Keri A. , Grinstaff Mark W. , Gerstenfeld Louis C.
Published: March 2016

A soluble form of BMP receptor type 1A (mBMPR1A‐mFC) acts as an antagonist to endogenous BMPR1A and has been shown to increase bone mass in mice. The goal of this study was to examine the effects of mBMPR1A‐mFC on secondary fracture healing. Treatment consisted of 10 mg/kg intraperitoneal injections of mBMPR1A‐mFC twice weekly in male C57BL/6 mice. Treatment beginning at 1, 14, and 21 days post‐fracture assessed receptor function during endochondral bone formation, at the onset of secondary bone formation, and during coupled remodeling, respectively. Control animals received saline injections. mBMPR1A‐mFC treatment initiated on day 1 delayed cartilage maturation in the callus and resulted in large regions of fibrous tissue. Treatment initiated on day 1 also increased the amount of mineralized tissue and up‐regulated many bone‐associated genes (p = 0.002) but retarded periosteal bony bridging and impaired strength and toughness at day 35 (p < 0.035). Delaying the onset of treatment to day 14 or 21 partially mitigated these effects and produced evidence of accelerated coupled remodeling. These results indicate that inhibition of the BMPR1A‐mediated signaling has negative effects on secondary fracture healing that are differentially manifested at different stages of healing and within different cell populations. These effects are most pronounced during the endochondral period and appear to be mediated by selective inhibition of BMPRIA signaling within the periosteum. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2096–2105, 2016.
The Middle Pleistocene glacial evolution of northern East Anglia, UK: a dynamic tectonostratigraphic–parasequence approach
Authors: Lee Jonathan R. , Phillips Emrys , Rose James , Vaughan‐Hirsch David
Published: March 2016

The Middle Pleistocene glacial history of northern East Anglia is a controversial topic with differing opinions surrounding chronology, provenance and the relative stratigraphic framework. Reconciling the stratigraphic framework of the region is an essential first step to developing onshore–offshore geological models and a robust event‐driven chronological framework. Within this study a dynamic tectonostratigraphic–parasequence methodology is applied to deposits traditionally attributed to the Anglian Glaciation (Marine Isotope Stage 12). This approach offers an insight into ice‐bed coupling during glaciation and how evolving boundary conditions influenced glacier dynamics. Six major tectonostratigraphic–parasequence assemblages (A1–A6) are recognized in northern East Anglia and correlate with successive advances into the region of North Sea or Pennine lobes of the British Ice Sheet. Individual tectonostratigraphic–parasequence assemblages are bound at their base by a sedimentary contact or, more commonly, a glacitectonic zone. The geometry and structural characteristics of these glacitectonic zones reflect temporal and spatial variations in ice‐bed coupling (traction), a function of substrate rheology and, in turn, variations in lithology, porewater availability and thermo‐mechanical properties. The role of permafrost may also be significant, promoting proglacial/ice‐marginal thrust stacking in front of advancing ice and enhanced ice‐bed decoupling during subsequent overriding and subglacial till accretion. © 2016 British Geological Survey, NERC Journal of Quaternary Science © 2016 John Wiley & Sons Ltd
The δ18O stratigraphy of the Hoxnian lacustrine sequence at Marks Tey, Essex, UK: implications for the climatic structure of MIS 11 in Britain
Authors: Tye G. J. , Sherriff J. , Candy I. , Coxon P. , Palmer A. , McClymont E. L. , Schreve D. C.
Published: March 2016

Marine Isotope Stage 11 (MIS 11) is considered one of the best analogues for the Holocene. In the UK the long lacustrine sequence at Marks Tey, Essex, spans the entirety of the Hoxnian interglacial, the British correlative of MIS 11c. We present multiproxy evidence from a new 18.5‐m core from this sequence. Lithostratigraphy, pollen stratigraphy and biomarker evidence indicate that these sediments span the pre‐, early and late temperate intervals of this interglacial as well as cold climate sediments that post‐date the Hoxnian. The δ18O signal of endogenic carbonate from this sequence produces several clear patterns that are interpreted as reflecting the climatic structure of the interglacial. As well as providing evidence for long‐term climate stability during the interglacial and a major post‐Hoxnian stadial/interstadial oscillation the δ18O signal provides strong evidence for abrupt cooling events during the interglacial itself. One of these isotopic events occurs in association with a short‐lived increase in non‐arboreal pollen (the NAP phase). The results presented here are discussed in the context of other MIS 11 records from Europe and the North Atlantic, particularly with respect to our understanding of the occurrence of abrupt climatic events in pre‐Holocene interglacials. Copyright © 2016 The Authors. Journal of Quaternary Science Published by John Wiley & Sons Ltd.
Iodide and iodate effects on the growth and fruit quality of strawberry
Authors: Li Rui , Liu Hui‐Ping , Hong Chun‐Lai , Dai Zi‐Xi , Liu Jia‐Wei , Zhou Jun , Hu Chun‐Qing , Weng Huan‐Xin
Published: March 2016

BACKGROUND

Iodine deficiency is an environmental health problem affecting one‐third of the global population. An iodine biofortification hydroponic experiment was conducted to explore the iodide and iodate uptake characteristics of strawberry plants, to measure the dosage effects of iodine on plant growth and to evaluate the influence of I− or IO3− application on fruit quality.

RESULTS

After biofortification, the iodine contents of the fresh strawberry fruits were 600–4000 µg kg−1, covering the WHO dietary iodine allowance of 150 µg · day−1 for adults. The iodine uptake of the strawberry plants increased with increasing I− or IO3− concentration of the culture solution. At the same iodine concentration, the iodate uptakes of various plant organs under I− treatments were apparently more than those under IO3− treatments. Low‐level exogenous iodine (I− ≤ 0.25 mg L−1 or IO3− ≤ 0.50 mg L−1) not only promoted plant growth and increased biomass per plant, but also improved fruit quality by enhancing the vitamin C and soluble sugar contents of the strawberry fruits. Nevertheless, excessive exogenous iodine inhibited plant growth and reduced biomass per plant. IO3− uptake apparently increased the total acidity and nitrate content of the fruits, reducing the quality of the strawberry fruits. Conversely, I− uptake obviously decreased the total acidity and nitrate content of the strawberry fruits, improving the fruit quality.

CONCLUSION

The strawberry can be used as a target crop for iodine biofortification. Furthermore, applying an appropriate dose of KI can improve the fruit quality of the strawberry plants. © 2016 Society of Chemical Industry
Quantification and semiquantification of multiple representative components for the holistic quality control of Allii Macrostemonis Bulbus by ultra high performance liquid chromatography with quadrupole time‐of‐flight tandem mass spectrometry
Authors: Qin Zifei , Lin Pei , Dai Yi , Yao Zhihong , Wang Li , Yao Xinsheng , Liu Liyin , Chen Haifeng
Published: March 2016

Allii Macrostemonis Bulbus (named Xiebai in China) is a folk medicine with medicinal values for the treatment of thoracic obstruction and cardialgia, and a food additive as well. However, there is even no quantitative standard for Allii Macrostemonis Bulbus recorded in the current edition of the Chinese Pharmacopeia. Hence, simultaneous assay of multiple components is urgent. In this study, chemometric methods were firstly applied to discover the components with significant fluctuation among multiple Allii Macrostemonis Bulbus samples based on optimized fingerprints. Meanwhile, the major components and main absorbed components in rats were all selected as its representative components. Subsequently, a sensitive method was established for the simultaneous determination of 54 components (15 components for quantification and 39 components for semiquantification) by ultra high performance liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry. Moreover, the validated method was successfully applied to evaluate the quality of multiple samples on the market. It became known that multiple Allii Macrostemonis Bulbus samples varied significantly and showed poor consistency. This work illustrated that the proposed approach could improve the quality of Allii Macrostemonis Bulbus, and it also provided a feasible method for quality evaluation of other traditional Chinese medicines.
Determination of fluoroquinolones in environmental water and milk samples treated with stir cake sorptive extraction based on a boron‐rich monolith
Authors: Mei Meng , Huang Xiaojia
Published: March 2016

In this study, a new stir cake sorptive extraction using a boron‐rich monolith as the adsorbent was prepared by the in situ copolymerization of vinylboronic anhydride pyridine complex and divinylbenzene. The effect of preparation parameters, including the ratio of vinylboronic anhydride pyridine complex and divinylbenzene, monomer mixture, and porogen solvent, on extraction performance was investigated thoroughly. The physicochemical properties of the adsorbent were characterized by infrared spectroscopy, scanning electron microscopy, and mercury intrusion porosimetry. Several conditions affecting the extraction efficiency were investigated in detail. Under the optimized conditions, a convenient and sensitive method for the determination of trace fluoroquinolones residues in water and milk samples was established by coupling stir cake sorptive extraction with high‐performance liquid chromatography and diode array detection. The limits of detection for the target compounds were 0.10–0.26 and 0.11–0.22 μg/L for water and milk samples, respectively. In addition, the developed method showed good linearity, repeatability, and precision. Finally, the proposed method was successfully applied for the detection of trace fluoroquinolones residues in environmental water and milk samples. Satisfactory recoveries were obtained for the determination of fluoroquinolones in spiking samples that ranged from 68.8 to 120%, with relative standard deviations below 10% in all cases.
Effects of lek count protocols on greater sage‐grouse population trend estimates
Authors: Monroe Adrian P. , Edmunds David R. , Aldridge Cameron L.
Published: March 2016

Annual counts of males displaying at lek sites are an important tool for monitoring greater sage‐grouse populations (Centrocercus urophasianus), but seasonal and diurnal variation in lek attendance may increase variance and bias of trend analyses. Recommendations for protocols to reduce observation error have called for restricting lek counts to within 30 minutes of sunrise, but this may limit the number of lek counts available for analysis, particularly from years before monitoring was widely standardized. Reducing the temporal window for conducting lek counts also may constrain the ability of agencies to monitor leks efficiently. We used lek count data collected across Wyoming during 1995−2014 to investigate the effect of lek counts conducted between 30 minutes before and 30, 60, or 90 minutes after sunrise on population trend estimates. We also evaluated trends across scales relevant to management, including statewide, within Working Group Areas and Core Areas, and for individual leks. To further evaluate accuracy and precision of trend estimates from lek count protocols, we used simulations based on a lek attendance model and compared simulated and estimated values of annual rate of change in population size (λ) from scenarios of varying numbers of leks, lek count timing, and count frequency (counts/lek/year). We found that restricting analyses to counts conducted within 30 minutes of sunrise generally did not improve precision of population trend estimates, although differences among timings increased as the number of leks and count frequency decreased. Lek attendance declined >30 minutes after sunrise, but simulations indicated that including lek counts conducted up to 90 minutes after sunrise can increase the number of leks monitored compared to trend estimates based on counts conducted within 30 minutes of sunrise. This increase in leks monitored resulted in greater precision of estimates without reducing accuracy. Increasing count frequency also improved precision. These results suggest that the current distribution of count timings available in lek count databases such as that of Wyoming (conducted up to 90 minutes after sunrise) can be used to estimate sage‐grouse population trends without reducing precision or accuracy relative to trends from counts conducted within 30 minutes of sunrise. However, only 10% of all Wyoming counts in our sample (1995−2014) were conducted 61−90 minutes after sunrise, and further increasing this percentage may still bias trend estimates because of declining lek attendance. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
Effect of multiple‐sweeping on ablation performance during ex vivo laser nephrectomy
Authors: Oh Junghwan , Nam Seung Yun , Lee Yong Wook , Kang Hyun Wook
Published: March 2016

Background and Objective

Fiber‐assisted laser surgery has been employed as a minimally invasive method in various medical fields. In spite of multiple sweeping on tissue during laser treatments, the rate of tissue removal gradually decreases and eventually leads to longer irradiation times as well as deeper thermal injury. The objective of the current study was to quantitatively investigate the effect of multiple fiber sweeps on ablation performance during ex vivo 532‐nm laser nephrectomy.

Materials and Methods

Porcine kidney tissue was used to evaluate variations in tissue ablation and coagulative necrosis after pre‐ and multiple‐sweeping with a 532 nm wavelength at various fiber speeds (2, 4, and 6 mm/second). The distance between a fiber tip and tissue surface was initially set at 1.5 mm, and no further distance change was performed. Double‐integrating spheres in conjunction with an adding‐doubling method were employed to measure variations in optical properties of the tested tissue. The extent of ablation and coagulation was quantified to identify the role of multiple‐sweeping at various fiber conditions.

Results

Optical property measurements showed a 30% decrease in light absorption but a more than threefold increase in light scattering after irreversible thermal denaturation. Pre‐sweeping yielded insignificant effects on tissue coagulation due to almost consistent coagulation depths with numbers of pre‐sweeps. Ablation depths increased with more numbers of fiber sweeps and slower fiber speeds whereas coagulation depths thickened primarily with the slower speeds. Multiple‐sweeping induced saturation in ablation volume with the increasing numbers of multiple‐sweeps irrespective of the fiber speed.

Conclusion

A combination of coagulation barriers, spatial distribution of power, and temporal interplay of optical energy could attribute to continuously lessen the amount of the ablated tissue with the multiple sweeps. Optical power modulation with varying fiber conditions (speed and distance) will be examined to optimize surgical parameters and to sustain the equivalent ablation performance of the first sweep with the multiple sweeping for laser nephrectomy. Lasers Surg. Med. 48:616–623, 2016. © 2016 Wiley Periodicals, Inc.
One‐Pot Synthesis of Double Poly(Ionic Liquid) Block Copolymers by Cobalt‐Mediated Radical Polymerization‐Induced Self‐Assembly (CMR‐PISA) in Water
Authors: Cordella Daniela , Debuigne Antoine , Jérôme Christine , Kochovski Zdravko , Taton Daniel , Detrembleur Christophe
Published: March 2016

Amphiphilic double poly(ionic liquid) (PIL) block copolymers are directly prepared by cobalt‐mediated radical polymerization induced self‐assembly (CMR‐PISA) in water of N‐vinyl imidazolium monomers carrying distinct alkyl chains. The cobalt‐mediated radical polymerization of N‐vinyl‐3‐ethyl imidazolium bromide (VEtImBr) is first carried out until high conversion in water at 30 °C, using an alkyl bis(acetylacetonate)cobalt(III) adduct as initiator and controlling agent. The as‐obtained hydrophilic poly(N‐vinyl‐3‐ethyl imidazolium bromide) (PVEtImBr) is then used as a macroinitiator for the CMR‐PISA of N‐vinyl‐3‐octyl imidazolium bromide (VOcImBr). Self‐assembly of the amphiphilic PVEtImBr‐b‐PVOcImBr block copolymer, i.e., of PIL‐b‐PIL‐type, rapidly takes place in water, forming polymer nanoparticles consisting of a hydrophilic PVEtImBr corona and a hydrophobic PVOcImBr core. Preliminary investigation into the effect of the size of the hydrophobic block on the dimension of the nanoparticles is also described.

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Loss of Nigral Hyperintensity on 3 Tesla MRI of Parkinsonism: Comparison With 123I‐FP‐CIT SPECT
Authors: Bae Yun Jung , Kim Jong‐Min , Kim Eunhee , Lee Kyung Mi , Kang Seo Young , Park Hyun Soo , Kim Kyeong Joon , Kim Young Eun , Oh Eung Seok , Yun Ji Young , Kim Ji Seon , Jeong Hye‐Jin , Jeon Beomseok , Kim Sang Eun
Published: March 2016

Background

The aim of this study was to investigate whether 3 Tesla susceptibility‐weighted imaging can detect the alteration of substantia nigra hyperintensity in Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) and to assess the concordance between the loss of nigral hyperintensity on 3 Tesla susceptibility‐weighted imaging and the nigrostriatal dopaminergic degeneration indicated by 123I‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)‐N‐(3‐fluoropropyl)‐nortropane single photon emission computerized tomography.

Methods

Consecutive subjects with suspected parkinsonism were included, and clinical diagnosis was solidified during clinical follow‐up. Two blinded neuroradiologists interpreted the nigral hyperintensity on susceptibility‐weighted imaging. The performance of susceptibility‐weighted imaging for detection of nigral hyperintensity loss was estimated on the basis of the clinical diagnosis and compared with single photon emission computerized tomography results.

Results

The study included 210 subjects (126 PD, 11 MSA, 11 PSP patients, 26 healthy controls, 36 disease controls). The presence or absence of nigral hyperintensity was accurately visualized in 112 PD, 7 MSA, and 11 PSP patients and 53 controls. We identified 16 false‐negative cases and 11 false‐positive cases. The sensitivity and specificity of susceptibility‐weighted imaging were 88.8% and 83.6%, respectively. The concordance rate between susceptibility‐weighted imaging and single photon emission computerized tomography was 86.2%.

Conclusions

The loss of nigral hyperintensity on susceptibility‐weighted imaging suggested nigrostriatal dopaminergic degeneration in a large portion of patients with parkinsonism, which was indicated by 123I‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)‐N‐(3‐fluoropropyl)‐nortropane single photon emission computerized tomography. In consideration of false‐negative and ‐positive cases, well‐designed imaging protocols should be introduced to improve the performance of nigral hyperintensity imaging. © 2016 International Parkinson and Movement Disorder Society
Error characteristics of temperature forecast in Finland for the period 1979–2011 in relation to various weather patterns
Authors: Hyrkkänen Juhana , Kilpinen Juha , Nurmi Pertti , Kaurola Jussi , Brockmann Matias
Published: March 2016

The investigation of weather forecast errors has focussed mainly on assessing the physical causes in numerical weather forecasting, such as errors in the initial state and model deficiencies. The framework and context of this paper are different. A 30 year time series (1979–2011) of 1 and 2 day human forecasts of temperature in Finland were used to investigate the statistical and climatological characteristics of maximum and minimum temperature forecast errors. Error dependence on different flow types and weather regimes was also analysed. The error statistics indicate that the forecast root‐mean‐square error has halved, and the forecast hit rate within a 2.5 °C error threshold has increased from 70% to 85–90% during the 30 year period. Large forecast errors of >5 °C are presently very rare, and they are mostly seen as positive biases in extreme cold temperatures and inversions. Otherwise, the forecasts nowadays are mostly unbiased with only small negative biases associated with Foehn events.

Forecast error extremes were found during winter, with a secondary peak in spring and under high pressure periods in non‐westerly and especially northeasterly airflows, dry air mass and relatively weak winds. The summertime maximum temperature errors are typically associated with opposite weather situations that occur most typically with cyclonic circulations, moist air masses and strong winds.
Correction of a 1 km daily rainfall dataset for modelling forest ecosystem processes in Italy
Authors: Fibbi Luca , Chiesi Marta , Moriondo Marco , Bindi Marco , Chirici Gherardo , Papale Dario , Gozzini Bernardo , Maselli Fabio
Published: March 2016

The availability of daily meteorological data over extended wide areas is a common requirement to model ecosystem processes on a regional scale. The meteorological dataset E‐OBS (European Observations) has been downscaled in 2012 to a 1 km spatial resolution in Italy. The assessment of this dataset against ground measurements revealed a marked under‐estimation of rainfall, which is a major driving factor for vegetation growth in water‐limited Mediterranean environments. The objective of the present study is to correct the downscaled rainfall dataset through the use of additional ground meteorological data collected over a 30 year period (1981–2010). The corrected dataset was evaluated using the ecosystem process model BIOME‐BGC (BioGeochemical Cycles). After identifying the most under‐estimated areas, seven sites that were representative of different forest ecosystems were selected; for each of these sites, gross primary production (GPP) was simulated using the E‐OBS original and corrected rainfall datasets. The test was completed for one site in central Italy (IT‐Ro2), assessing the outputs of the BIOME‐BGC data versus the daily GPP data obtained by the eddy correlation technique. In all cases, the use of the corrected dataset produced more realistic GPP simulations; for IT‐Ro2, the mean bias error was 0.18 instead of 2.33 g C m−2 day−1. The beneficial effect of the correction depended on the aridity of the examined site, that is, it was the maximum in the driest Mediterranean ecosystems and almost null in the most humid environments. It can therefore be concluded that the corrected dataset is suitable to drive the long‐term simulation of forest ecosystem processes in all Italian eco‐climatic conditions.
Identification of pinostilbene as a major colonic metabolite of pterostilbene and its inhibitory effects on colon cancer cells
Authors: Sun Yue , Wu Xian , Cai Xiaokun , Song Mingyue , Zheng Jinkai , Pan Che , Qiu Peiju , Zhang Lijuan , Zhou Shuangde , Tang Zhonghai , Xiao Hang
Published: March 2016

Scope

Pterostilbene (PTE) is a resveratrol derivative mainly found in blueberries, and it has been shown to inhibit colon carcinogenesis in multiple animal models. To shed light on the mechanism of PTE in inhibiting colon carcinogenesis, we investigated the PTE metabolites in the mouse colon and in the human colon cancer cells.

Methods and results

CD‐1 mice were fed PTE‐containing diet for 3 weeks, and colonic content and colonic mucosa were collected and subjected to LC‐MS analysis. Pinostilbene (PIN) was identified as a major metabolite of PTE in the mouse colon. Importantly, the level of PIN was found to be approximately equivalent to that of PTE in the colonic mucosa. PIN significantly inhibited the growth of human colon cancer cells, i.e., HCT116 and HT29. These inhibitory effects were similar to those produced by PTE. Moreover, under physiologically relevant conditions, 20 and 40 μM of PIN caused cell cycle arrest at S phase and induced apoptosis in colon cancer cells. These effects were associated with profound modulation of signaling proteins related with cell proliferation and programmed cell death.

Conclusion

Our results demonstrated that PIN is a major metabolite of PTE in the colon of mice fed with PTE, and PIN may play important roles in the anti‐colon cancer effects elicited by orally administered PTE.
Maternal high‐salt diet altered PKC/MLC20 pathway and increased ANG II receptor‐mediated vasoconstriction in adult male rat offspring
Authors: Li Weisheng , Lv Juanxiu , Wu Jue , Zhou Xiuwen , Jiang Lin , Zhu Xiaolin , Tu Qing , Tang Jiaqi , Liu Yanping , He Axin , Zhong Yuan , Xu Zhice
Published: March 2016

Scope

High‐salt diet (HSD) is associated with cardiovascular diseases. This study aims at ascertaining the influence of maternal HSD on offspring's angiotensin II (ANG II)‐mediated vasoconstriction and the underlying mechanisms.

Methods and results

In comparison to a normal‐salt diet, HSD used in pregnancy in rats changed the ultrastructures of the coronary artery (CA) in 5‐month‐old male offspring, and increased ANG II‐mediated CA contractility. Measurement of [Ca2+]i in CA using fluorescent fura‐2, a Ca2+ indicator, showed that ANG II‐mediated increases in [Ca2+]i were the same between HSD and normal‐salt diet groups, but the ratio of diameter change/[Ca2+]i induced by ANG II were significantly higher in HSD groups. Angiotensin II receptor type 1, not angiotensin II receptor type 2, caused ANG II‐mediated vasoconstriction. Protein kinase C (PKC) inhibitor GF109203X attenuated the ANG II‐mediated vasoconstriction, PKC agonist phorbol12,13‐dibutyrate produced a greater contraction. There was an increase in PKCβ mRNA and the corresponding protein abundance in the offspring, whereas other PKC subunits PKCα, PKCδ, and PKCε did not change. Moreover, 20 kDa myosin light chain phosphorylation levels were increased in HSD group.

Conclusion

Maternal HSD affected the developmental programing for the offspring CA, with increased ANG II‐mediated vasoconstrictions. The angiotensin II receptor type 1‐PKC‐20 kDa myosin light chain phosphorylation pathway was the possible mediated cellular mechanism.
Polyphenol rich olive oils improve lipoprotein particle atherogenic ratios and subclasses profile: A randomized, crossover, controlled trial
Authors: Fernández‐Castillejo Sara , Valls Rosa‐Maria , Castañer Olga , Rubió Laura , Catalán Úrsula , Pedret Anna , Macià Alba , Sampson Maureen L. , Covas María‐Isabel , Fitó Montserrat , Motilva Maria‐José , Remaley Alan T. , Solà Rosa
Published: March 2016

Scope

Lipoprotein particle measures performed by nuclear magnetic resonance (NMR), and associated ratios, may be better markers for atherosclerosis risk than conventional lipid measures. The effect of two functional olive oils, one enriched with its polyphenols (FVOO, 500 ppm), and the other (FVOOT) with them (250 ppm) and those of thyme (250 ppm), versus a standard virgin olive oil (VOO), on lipoprotein particle atherogenic ratios and subclasses profiles was assessed.

Methods and results

In a randomized, double‐blind, crossover, controlled trial, 33 hypercholesterolemic individuals received 25 mL/day of VOO, FVOO, and FVOOT. Intervention periods were of 3 weeks separated by 2‐week washout periods. Lipoprotein particle counts and subclasses were measured by NMR. Polyphenols from olive oil and thyme modified the lipoprotein subclasses profile and decreased the total LDL particle/total HDL particle (HDL‐P), small HDL/large HDL, and HDL‐cholesterol/HDL‐P ratios, and decreased the lipoprotein insulin resistance index (LP‐IR) (p < 0.05).

Conclusion

Olive oil polyphenols, and those from thyme provided benefits on lipoprotein particle atherogenic ratios and subclasses profile distribution. Polyphenol‐enriched olive oil is a way of increasing the olive oil healthy properties while consuming the same amount of fat, as well as a useful and complementary tool for the management of cardiovascular risk individuals.
Prediction of195Pt NMR chemical shifts of dissolution products of H2[Pt(OH)6] in nitric acid solutions by DFT methods: how important are the counter‐ion effects?
Authors: Tsipis Athanassios C. , Karapetsas Ioannis N.
Published: March 2016

195Pt NMR chemical shifts of octahedral Pt(IV) complexes with general formula [Pt(NO3)n(OH)6 − n]2−, [Pt(NO3)n(OH2)6 − n]4 − n(n = 1–6), and [Pt(NO3)6 − n − m(OH)m(OH2)n]−2 + n − mformed by dissolution of platinic acid, H2[Pt(OH)6], in aqueous nitric acid solutions are calculated employing density functional theory methods. Particularly, the gauge‐including atomic orbitals (GIAO)‐PBE0/segmented all‐electron relativistically contracted–zeroth‐order regular approximation (SARC–ZORA)(Pt) ∪ 6–31G(d,p)(E)/Polarizable Continuum Model computational protocol performs the best. Excellent second‐order polynomial plots ofδcalcd(195Pt)versus δexptl(195Pt) chemical shifts andδcalcd(195Pt)versusthe natural atomic chargeQPtare obtained. Despite of neglecting relativistic and spin orbit effects the good agreement of the calculatedδ195Pt chemical shifts with experimental values is probably because of the fact that the contribution of relativistic and spin orbit effects to computedσiso195Pt magnetic shielding of Pt(IV) coordination compounds is effectively cancelled in the computedδ195Pt chemical shifts, because the relativistic corrections are expected to be similar in the complexes and the proper reference standard used. To probe the counter‐ion effects on the195Pt NMR chemical shifts of the anionic [Pt(NO3)n(OH)6 − n]2−and cationic [Pt(NO3)n(OH2)6 − n]4 − n(n = 0–3) complexes we calculated the195Pt NMR chemical shifts of the neutral (PyH)2[Pt(NO3)n(OH)6 − n] (n = 1–6; PyH = pyridinium cation, C5H5NH+) and [Pt(NO3)n(H2O)6 − n](NO3)4 − n(n = 0–3) complexes. Counter‐anion effects are very important for the accurate prediction of the195Pt NMR chemical shifts of the cationic [Pt(NO3)n(OH2)6 − n]4 − ncomplexes, while counter‐cation effects are less important for the anionic [Pt(NO3)n(OH)6 − n]2−complexes. The simple computational protocol is easily implemented even by synthetic chemists in platinum coordination chemistry that dispose limited software availability, or locally existing routines and knowhow. Copyright © 2016 John Wiley & Sons, Ltd.
In vivo detection of 2‐hydroxyglutarate in brain tumors by optimized point‐resolved spectroscopy (PRESS) at 7T
Authors: Ganji Sandeep K. , An Zhongxu , Tiwari Vivek , McNeil Sarah , Pinho Marco C. , Pan Edward , Mickey Bruce E. , Maher Elizabeth A. , Choi Changho
Published: March 2016

Purpose

To test the efficacy of 7T MRS for in vivo detection of 2‐hydroxyglutarate (2HG) in brain tumors.

Methods

The subecho times of point‐resolved spectroscopy (PRESS) were optimized at 7T with density‐matrix simulations and phantom validation to improve the 2HG signal selectivity with respect to the neighboring resonances of γ‐aminobutyric acid (GABA), glutamate (Glu), and glutamine (Gln). MRS data were acquired from 12 subjects with gliomas in vivo and analyzed with LCModel using calculated basis spectra. Metabolite levels were quantified using unsuppressed short echo time (TE) water as a reference.

Results

The PRESS TE was optimized as TE = 78 ms (TE1 = 58 ms and TE2 = 20 ms), at which the 2HG 2.25 ppm resonance appeared as a temporally maximum inverted narrow peak and the GABA, Glu, and Gln resonances between 2.2 and 2.5 ppm were all positive peaks. The PRESS TE = 78 ms method offered improved discrimination of 2HG from Glu, Gln, and GABA when compared with short‐TE MRS. 2HG was detected in all patients enrolled in the study, the estimated 2HG concentrations ranging from 1.0 to 6.2 mM, with percentage standard deviation of 2%–7%.

Conclusion

Data indicate that the optimized MRS provides good selectivity of 2HG from other metabolite signals and may confer reliable in vivo detection of 2HG at relatively low concentrations. Magn Reson Med 77:936–944, 2017. © 2016 International Society for Magnetic Resonance in Medicine