bluuebunny/crossref_metadata_2025 huggingface dataset:
Myoferlin plays a key role in VEGFA secretion and impacts tumor‐associated angiogenesis in human pancreas cancer
Authors: Fahmy Karim , Gonzalez Arnaud , Arafa Mohammad , Peixoto Paul , Bellahcène Akeila , Turtoi Andrei , Delvenne Philippe , Thiry Marc , Castronovo Vincent , Peulen Olivier
Published: August 2015

Pancreatic ductal adenocarcinoma is one of the most deadly forms of cancers with no satisfactory treatment to date. Recent studies have identified myoferlin, a ferlin family member, in human pancreas adenocarcinoma where its expression was associated to a bad prognosis. However, the function of myoferlin in pancreas adenocarcinoma has not been reported. In other cell types, myoferlin is involved in several key plasma membrane processes such as fusion, repair, endocytosis and tyrosine kinase receptor activity. In this study, we showed that myoferlin silencing in BxPC‐3 human pancreatic cancer cells resulted in the inhibition of cell proliferation in vitro and in a significant reduction of the tumor volume in chick chorioallantoic membrane assay. In addition to be smaller, the tumors formed by the myoferlin‐silenced cells showed a marked absence of functional blood vessels. We further demonstrated that this effect was due, at least in part, to an inhibition of VEGFA secretion by BxPC‐3 myoferlin‐silenced cells. Using immunofluorescence and electron microscopy, we linked the decreased VEGFA secretion to an impairment of VEGFA exocytosis. The clinical relevance of our results was further strengthened by a significant correlation between myoferlin expression in a series of human pancreatic malignant lesions and their angiogenic status evaluated by the determination of the blood vessel density.
Prognostic and diagnostic potential of local and circulating levels of pentraxin 3 in lung cancer patients
Authors: Infante Maurizio , Allavena Paola , Garlanda Cecilia , Nebuloni Manuela , Morenghi Emanuela , Rahal Daoud , Roncalli Massimo , Cavuto Silvio , Pesce Samantha , Monari Marta , Valaperta Serenella , Montanelli Alessandro , Solomon Daniel , Bottoni Edoardo , Errico Valentina , Voulaz Emanuele , Bossi Manuela , Chiesa Giuseppe , Passera Eliseo , Mantovani Alberto , Alloisio Marco
Published: August 2015

There is a well‐established link between inflammation and cancer of various organs, but little data are available on inflammation‐associated markers of diagnostic and prognostic clinical utility in pulmonary malignancy. Blood samples were prospectively collected from 75 resectable lung cancer patients before surgery and in a cohort of 1,358 high‐risk subjects. Serum levels of long pentraxin 3 (PTX3) were determined by high‐sensitivity ELISA. PTX3 immunostaining was evaluated by immunohistochemistry in cancer tissue. Serum PTX3 levels in the high‐risk population were not predictive of developing subsequent lung cancer or any other malignancy; however, serum PTX3 values in patients with lung cancer were significantly higher compared with cancer‐free heavy smokers. With a cutoff of 4.5 ng/ml, specificity was 0.80, sensitivity 0.69, positive predictive value 0.15 and negative predictive value 0.98. The receiver operating curve (ROC) for serum PTX3 had an area under the curve (AUC) of 83.52%. Preoperative serum PTX3 levels in lung cancer patients did not correlate with patient outcome, but high interstitial expression of PTX3 in resected tumor specimens was a significant independent prognostic factor associated with shorter survival (p < 0.001). These results support the potential of serum PTX3 as a lung cancer biomarker in high‐risk subjects. Furthermore, PTX3 immunohistochemistry findings support the role of local inflammatory mechanisms in determining clinical outcome and suggest that local expression of PTX3 may be of prognostic utility in lung cancer patients.
A general exit strategy of monoheme cytochromes c and c2 in electron transfer complexes?
Authors: De March Matteo , Brancatelli Giovanna , Demitri Nicola , De Zorzi Rita , Hickey Neal , Geremia Silvano
Published: August 2015

Using our previously reported maps of the electrostatic surface of horse heart ferri‐ and ferro‐cyt c, comparisons were made between the complementary electrostatic surfaces of three cyt c peroxidase–cyt c complexes and the photosynthetic reaction center–cyt c complex, considering both iron oxidation states. The results obtained were consistent with a sliding mechanism for the electron shuttle on the surface of the protein complexes, promoted by the change in iron oxidation state. This mechanism was found to be in agreement with theoretical and NMR studies reported in the literature. Importantly, the analysis also provided a rationale for recognition of nonproductive associations. As we have previously reported the same conclusion on examination of redox partners of cyt c in the mitochondrial respiratory pathway, our hypothesis is that the proposed mechanism could represent a general exit strategy of monoheme cyts c and c2 in electron transfer complexes. © 2015 IUBMB Life, 67(9):694–700, 2015
Application of a BOSS—Gaussian interface for QM/MM simulations of Henry and methyl transfer reactions
Authors: Vilseck Jonah Z. , Kostal Jakub , Tirado‐Rives Julian , Jorgensen William L.
Published: August 2015

Hybrid quantum mechanics and molecular mechanics (QM/MM) computer simulations have become an indispensable tool for studying chemical and biological phenomena for systems too large to treat with QM alone. For several decades, semiempirical QM methods have been used in QM/MM simulations. However, with increased computational resources, the introduction of ab initio and density function methods into on‐the‐fly QM/MM simulations is being increasingly preferred. This adaptation can be accomplished with a program interface that tethers independent QM and MM software packages. This report introduces such an interface for the BOSS and Gaussian programs, featuring modification of BOSS to request QM energies and partial atomic charges from Gaussian. A customizable C‐shell linker script facilitates the interprogram communication. The BOSS–Gaussian interface also provides convenient access to Charge Model 5 (CM5) partial atomic charges for multiple purposes including QM/MM studies of reactions. In this report, the BOSS–Gaussian interface is applied to a nitroaldol (Henry) reaction and two methyl transfer reactions in aqueous solution. Improved agreement with experiment is found by determining free‐energy surfaces with MP2/CM5 QM/MM simulations than previously reported investigations using semiempirical methods. © 2015 Wiley Periodicals, Inc.
Simultaneous Spectrophotometric Determination of Sunset Yellow and Quinoline Yellow in a Single Step
Authors: Asadpour‐Zeynali Karim , Manafi‐Khoshmanesh Sara
Published: August 2015

In this work a new modified standard addition method for simultaneous spectrophotometric determination of Sunset yellow (SY) and Quinoline yellow (QY) is used. The generalized Net Analyte Signal Standard Addition Method (GNASSAM) was introduced for simultaneous standard addition of analytes. By applying this method the concentrations of analytes are determined in a single step. The applicability of new method was used for the simultaneous determination of strongly overlapped spectra of SY and QY in a real sample without using any separation step. GNASSAM was also used to calculate figures of merit. Moreover, good limits of detection (SY=0.13 and QY=0.16 mg L −1) and suitable selectivity and sensitivity were determined. HPLC method was applied for finding subspace in binary mixtures of real samples. The results of investigated method for real sample were compared with HPLC results. The obtained results were in a good agreement with those of HPLC method.
Organic Dyes Containing a 1,3‐indandione Moiety as Light Harvesting Materials
Authors: Chou Po‐Ting , Lin Yan‐Duo , Chang Yuan Jay , Liu Ching‐Yang , Chow Tahsin J.
Published: August 2015

Organic dipolar compounds containing a 1,3‐indandione‐5,6‐dicarboxylic acid moiety as an electron acceptor group were examined for the feasibility of using as the light harvesting material in dye‐sensitized solar cells. Two compounds with triphenylamine donor moieties were synthesized by attaching it to 1,3‐indandione‐5,6‐dicarboxylic acid. The device made with these simple dyes achieved a quantum yield up to 2.5 %, which is comparable to the widely used dye made with cyanoacrylic acid. The spectroscopic properties of these compounds were analysed with the aid of theoretical models according to the time‐dependent density functional theory.
Extended‐release but not immediate‐release and subcutaneous methylnaltrexone antagonizes the loperamide‐induced delay of whole‐gut transit time in healthy subjects
Authors: Kolbow Julia , Modess Christiane , Wegner Danilo , Oswald Stefan , Maritz Martina Alice , Rey Hélène , Weitschies Werner , Siegmund Werner
Published: August 2015

Methylnaltrexone (MNTX) is approved for subcutaneous treatment (MNTX‐SC) of opioid induced constipation. MNTX in oral immediate‐release (MNTX‐IR) and extended‐release (MNTX‐ER) dosage forms may antagonize the opioid induced delay in oro‐cecal transit time (OCT) as measured by using radiolabeled lactulose. Because lactulose acts laxative by its own and efficacy of MNTX on colon transit time (CTT) was unknown, the opioid antagonistic effects MNTX‐IR and MNTX‐ER (both 500 mg) relative to MNTX‐SC (12 mg) were evaluated in 15 healthy subjects with loperamide (LOP, 3 × 4 mg, 12 hourly) induced experimental constipation using the sulfasalazine/sulfapyridine method and radio‐opaque markers to measure OCT and whole gut transit time (WGT). MNTX‐ER significantly antagonized the LOP effects in 12 of our 15 subjects who responded to LOP with prolongation of WGT by 20.6–74.1 h (OCT by 0.50–10.5 h, CTT by 18.3–73.6 h). MNTX‐SC and MNTX‐IR were without significant influence. Compared to MNTX‐SC, bioavailability of MNTX‐IR and MNTX‐ER was 1.53–5.49 % and 0.11–1.24 %, respectively. MNTX‐SC and MNTX‐IR achieved active serum levels only for ∼3–5 h. MNTX‐ER antagonized the opioid‐induced delay of CTT most likely by local effects on µ‐opioid receptors in the colon.
Effects of UGT1A1 genotype on the pharmacokinetics, pharmacodynamics, and toxicities of belinostat administered by 48‐hour continuous infusion in patients with cancer
Authors: Goey Andrew K. L. , Sissung Tristan M. , Peer Cody J. , Trepel Jane B. , Lee Min‐Jung , Tomita Yusuke , Ehrlich Sheryl , Bryla Christine , Balasubramaniam Sanjeeve , Piekarz Richard , Steinberg Seth M. , Bates Susan E. , Figg William D.
Published: August 2015

The histone deacetylase inhibitor belinostat is eliminated through glucuronidation by UGT1A1. Polymorphisms that reduce UGT1A1 function could result in increased belinostat exposure and toxicities. We wanted to determine which single‐nucleotide polymorphisms alter belinostat exposure and toxicity. In a phase 1 trial (belinostat over 48 hours in combination with cisplatin and etoposide), belinostat (400, 500, 600, or 800 mg/m2/24 h, 48‐hour continuous infusion) was administered to patients with cancer in combination with cisplatin and etoposide (n = 25). Patients were genotyped for UGT1A1 variants associated with reduced function: UGT1A1*6, UGT1A1*28, and UGT1A1*60. End points were associations between UGT1A1 genotype and belinostat pharmacokinetics (PK), toxicities, and global protein lysine acetylation (AcK). Belinostat AUC was increased (P = .003), and t1/2 increased (P = .0009) in UGT1A1*28 and UGT1A1*60 carriers who received more than 400 mg/m2/24 h. The incidence of grades 3–4 thrombocytopenia (P = .0081) was associated with UGT1A1 polymorphisms. The US Food and Drug Administration–approved package insert recommends dose adjustment of belinostat for UGT1A1*28. However, our data suggest dose adjustment is also necessary for UGT1A1*60. UGT1A1 polymorphisms were associated with increased systemic belinostat exposure, increased AcK, and increased incidence of toxicities, particularly at doses > 400 mg/m2/24 h.
A Convenient Alternative Route for the Synthesis of Bis(2,5‐dimethylpyrrolo[3,4‐d])tetrathiafulvalene
Authors: Solano M. V. , Nielsen M. B. , Jeppesen J. O.
Published: August 2015

An alternative and efficient protocol for the synthesis of methylated pyrrolo‐tetrathiafulvalenes have been developed. The key intermediate in this new synthetic protocol is 4,6‐dimethyl‐N‐tosyl‐(1,3)‐dithiolo[4,5‐c]pyrrole‐2‐one, which can be obtained in high yield in a three‐step synthetic procedure from 5‐dimethyl‐3,4‐dithiocyanopyrrole.
Overexpression of miR‐18a negatively regulates myocyte enhancer factor 2D to increase the permeability of the blood–tumor barrier via Krüppel‐like factor 4‐mediated downregulation of zonula occluden‐1, claudin‐5, and occludin
Authors: Zhao Ying‐Yu , Zhao Li‐Ni , Wang Ping , Miao Yin‐Sha , Liu Yun‐Hui , Wang Zhen‐Hua , Ma Jun , Li Zhen , Li Zhi‐Qing , Xue Yi‐Xue
Published: August 2015

miR‐18a represses angiogenesis and tumor evasion by weakening vascular endothelial growth factor and transforming growth factor‐β signaling to prolong the survival of glioma patients, although it is thought to be an oncogene. This study investigates the potential effects of miR‐18a on the permeability of the blood–tumor barrier (BTB) and its possible molecular mechanisms. An in vitro BTB model was successfully established. The endogenous expression of miR‐18a in glioma vascular endothelial cells (GECs) was significantly lower than that in normal vascular ECs, and the overexpression of miR‐18a significantly increased the permeability of the BTB as well as downregulating the mRNA and protein expressions of tight junction‐related proteins zonula occluden‐1 (ZO‐1), claudin‐5, and occludin in GECs. Dual luciferase reporter assays revealed that miR‐18a bound to the 3′‐untranslated region (3′UTR) of myocyte enhancer factor 2D (MEF2D). The overexpression of both miR‐18a and MEF2D with the 3′UTR significantly weakened the effect caused by miR‐18a of decreasing the mRNA and protein expressions of ZO‐1, claudin‐5 and occludin and of increasing the permeability of the BTB. Chromatin immunoprecipitation showed that MEF2D could directly bind to KLF4 promoter. This study shows that miR‐18a targets and negatively regulates MEF2D, which further regulates tight junction‐related proteins ZO‐1, claudin‐5, and occludin through transactivation of KLF4 and, finally, changes the permeability of the BTB. MiR‐18a should garner growing attention because it might serve as a potential target in opening the BTB and providing a new strategy for the treatment of gliomas. © 2015 Wiley Periodicals, Inc.
Characterization of 6‐propylthiouracil and its interaction with human serum albumin on Au surface by surface‐enhanced Raman scattering
Authors: Li Panfang , Gu Huaimin
Published: August 2015

In this study, surface‐enhanced Raman scattering (SERS) spectra of 6‐propylthiouracil (6‐PTU) on Au surface and the interaction between 6‐PTU and human serum albumin (HSA) were studied. The Raman bands were assigned by the density functional theory calculations at the B3LYP/6‐311++g(d,p) level. Furthermore, the effects of concentration on the SERS spectra of 6‐PTU were analyzed. It shows that with the changes of the concentrations of 6‐PTU, the SERS spectra of 6‐PTU present significant changes, and it can be concluded that with the changing of concentrations, the orientation of 6‐PTU on Au surface also changes. In addition, the SERS spectra of the interaction between 6‐PTU and HSA show that the binding sites of 6‐PTU to HSA are the functional groups N3H and CO. The information will not only be references to the study of the mechanism of the interaction between drugs and blood plasma or serum albumin but also a guidance to understand the metabolism of drugs in human body. Copyright © 2015 John Wiley & Sons, Ltd.
Robot‐assisted radical cystectomy
Authors: Kurpad Raj , Woods Michael
Published: August 2015

Robot‐assisted radical cystectomy (RARC) has rapidly penetrated the field of urology since its inception in 2003. Several observational studies, retrospective reports, and three randomized controlled trials (RCT) have preliminarily demonstrated the safety and efficacy of (RARC). Additionally, results from the RAZOR RCT will be available in 2016–2017 to better substantiate the use of (RARC).J. Surg. Oncol. 2015;112:728–735. © 2015 Wiley Periodicals, Inc.
The impact of sarcopenia on survival and complications in surgical oncology: A review of the current literature
Authors: Joglekar Savita , Nau Peter N. , Mezhir James J.
Published: August 2015

Sarcopenia is the subclinical loss of skeletal muscle and strength and has been extensively studied in both the cancer and surgical literature. Specifically, sarcopenia has gained significant recognition as an important prognostic factor for both complications and survival in cancer patients. Herein, we review the current literature to date highlighting the specific impact of sarcopenia in patients undergoing oncologic procedures. J. Surg. Oncol. 2015; 112:503–509. © 2015 Wiley Periodicals, Inc.
Evaluation of a multi‐fiber exchange solid‐phase microextraction system and its application to on‐site sampling
Authors: Gómez‐Ríos German A. , Reyes‐Garcés Nathaly , Pawliszyn Janusz
Published: August 2015

Until recently, multiple solid‐phase microextraction fibers could not be automatically desorbed in a single gas chromatographic sequence without manual intervention from an operator. This drawback had been a critical issue, particularly during the analysis of numerous on‐site samples taken with various fiber assemblies. Recently, a Multi‐Fiber Exchange system, designed to overcome this flaw found in other commercially available autosamplers, was released. In the current research, a critical evaluation of the Multi‐Fiber Exchange system performance in terms of storage stability and long‐term operation is presented. It was established in the course of our research that the Multi‐Fiber Exchange system can operate continuously and precisely for multiple extraction/injection cycles. However, when the effect of residence time of commercial fibers on the Multi‐Fiber Exchange tray was evaluated, results showed that among the evaluated fiber coatings, Carboxen/polydimethylsiloxane was the only coating capable of efficient storage on the tray for up to 24 h after field sampling without suffering significant loss of analytes (≤10% for benzene, toluene, ethylbenzene, o‐xylene, decane, and limonene). Additionally, the system capability for high‐throughput analysis was demonstrated by the unattended desorption of multiple fibers after on‐site sampling of toluene, indoor air levels, in a polymer synthesis lab.
Preparative separation of bioactive constitutes from Zanthoxylum planispinum using linear gradient counter‐current chromatography
Authors: Zhang Yanping , Cheng Zhuo , Lu Yanbin
Published: August 2015

Counter‐current chromatography is a chromatographic technique with a support‐free liquid stationary phase. In the present study, a successful application of linear gradient counter‐current chromatographic method for preparative isolation of bioactive components from the crude ethanol extract of Zanthoxylum planispinum was presented. The application of n‐hexane/ethyl acetate/methanol/water quaternary solvents, in terms of “HEMWat” or “Arizona” solvent families, in gradient elution mode was evaluated. Results indicated that slightly proportional changes of biphasic liquid systems provided the possibility of gradient elution in counter‐current chromatography, maintaining stationary phase retention in the column. With the selected quaternary solvent systems composed of n‐hexane/ethyl acetate/methanol/water (2:1:2:1 and 3:2:3:2, v/v), and optimized gradient programs, in total seven fractions were separated in 4.5 h. Most of the purified compounds could be obtained at the milligram level with over 80% purity. The present study indicated that the linear gradient counter‐current chromatographic approach possessed unique advantages in terms of separation efficiency, exhibiting great potential for the comprehensive separation of complex natural extracts.
Octyl‐modified magnetic graphene as a sorbent for the extraction and simultaneous determination of fragrance allergens, musks, and phthalates in aqueous samples by gas chromatography with mass spectrometry
Authors: Maidatsi Katerina V. , Chatzimitakos Theodoros G. , Sakkas Vassilios A. , Stalikas Constantine D.
Published: August 2015

An effective, simple, and low‐cost sample preparation method based on dispersive SPE followed by GC with MS is developed for the multianalyte determination of fragrance allergens, musks, and phthalates, at sub‐ppb levels. The extraction procedure is based on a novel magnetic graphene sorbent, which is functionalized with octylamine, taking advantage of the functionalization's hydrophobic properties and π–π interactions with the analytes. Two alkyl amines, the octylamine and octadecylamine are studied to introduce alkyl chains in the basal plane of graphene. Magnetic graphene‐ octadecylamine is proved to be highly hydrophobic to such a degree that is hard to disperse in the bulk aqueous matrixes. Because of this behavior, its extraction efficiency for the target analytes is low. The synthesis and applicability of the magnetic graphene‐octylamine as more favored sorbent are optimized in terms of the most determining experimental conditions. The detection and quantification limits, which are calculated based on S/N ratio of 3 and 10, respectively, ranged from 0.29 to 3.2 ng L−1 and from 0.89 to 9.6, respectively. The dispersive SPE is successfully applied to routine analysis for the determination of the target analytes in samples from municipal treatment plant of Ioannina (Greece), from Pamvotis Lake and baby bathwater. The reproducibility of the spiked biological treatment plant water sample is evaluated and the relative standard deviation values range between 2.1 and 9.4%.
Comparison of extraction solvents and sorbents in the quick, easy, cheap, effective, rugged, and safe method for the determination of pesticide multiresidue in fruits by ultra high performance liquid chromatography with tandem mass spectrometry
Authors: Liu Shaoying , He Huali , Huang Xihui , Jin Quan , Zhu Guonian
Published: August 2015

An improved analytical method was developed for the simultaneous quantification of several plant growth regulators and fungicides (carbendazim, pyrimethanil, metalaxyl, triadimefon, paclobutrazol, thiophanate, prochloraz, dimethomorph, difenoconazole, (4‐chlorophenoxy)‐acetic acid, (2,4‐dichlorophenoxy)‐acetic acid, thiadiazuron, forchlorfenuron and gibberellins) in fruits followed by ultra high performance liquid chromatography with tandem mass spectrometry. Samples were extracted and purified using a modified QuEChERS method. Different extraction solvents and sorbents in the QuEChERS method were compared. Optimum results were followed by the addition of 1% acetic acid in acetonitrile; C18 sorbent was added due to the acidic nature of several pesticides. The recoveries of the pesticides were in the range 73.7–118.4%, with relative standard deviations lower than 16.63%. Limits of detection ranged from 0.1–1.0 μg/kg. The method presented here is simple, rapid, sensitive and can be applied to large‐scale monitoring programs to screen the presences of pesticides in fruits.
Molecularly imprinted polymers for the solid‐phase extraction of four fluoroquilones from milk and lake water samples
Authors: Wu Xi , Wu Lintao
Published: August 2015

A method based on molecular crowding and ionic liquids as reaction solvents has been used for the synthesis of molecularly imprinted polymers. Levofloxacin was selected as the template, polymethyl methacrylate was the molecular crowding agent, and 1‐butyl‐3‐methylimidazolium tetrafluoroborate (ionic liquid) was selected as the reaction solvent and porogen. The optimized proportion for the mixed porogen was dimethyl sulfoxide/ionic liquid/polymethyl methacrylate 1:1.6:5 in chloroform (150 mg mL−1). The morphology and chemical composition of levofloxacin imprinted polymers were assessed by scanning electron microscopy and Fourier transform infrared spectroscopy. The absorption experiments demonstrated that the levofloxacin imprinted polymers possess high selective recognition property to levofloxacin and analogs, including enrofloxacin, ciprofloxacin and gatifloxacin, which all belong to fluoroquinolones. An extraction method using levofloxacin imprinted polymers as sorbent followed by high‐performance liquid chromatography analysis was optimized for the determination of four fluoroquinolones in milk and lake water samples. Under the optimized conditions, good linearity was observed in a range of 5–1000 ng g−1 with the limit of detection between 0.3 and 0.5 ng g−1 for the four fluoroquinolones. The recoveries at three spiked levels ranged 82.4–98.3% with the relative standard deviation ≤4.9.
Stepped gradients on polymeric monolithic columns by photoinitiated grafting
Authors: Currivan Sinéad , Connolly Damian , Paull Brett
Published: August 2015

The surface of polymethacrylate monoliths was functionalized by a post‐polymerization modification, by means of a novel photo‐initiated graft procedure where the charged monomer, sulfopropyl methacrylate, was controllably grafted stepwise, i.e. with incremental graft energies. The grafting approach was optimized using scanning capacitively coupled contactless conductivity detection. The effect of the localized ion exchange capacity and resultant gradient stationary phase upon ion‐exchange chromatographic retention, selectivity, and performance was investigated, and compared to a homogeneously grafted (isotropic) column. The gradient column provided reduced peak widths at half height for both cationic analytes, with a reduction of 34 and 33%, respectively, when compared to the isotropic column.
Predicting mule deer recruitment from climate oscillations for harvest management on the northern Great Plains
Authors: Ciuti Simone , Jensen William F. , Nielsen Scott E. , Boyce Mark S.
Published: August 2015

We analyzed a unique 51‐year time series for a population of mule deer in the North Dakota badlands, USA to examine the effects of seasonal weather on autumn recruitment. Winter weather recorded prior to birth of fawns and weather conditions recorded during spring the previous year (lagged effect), but not during spring or summer after birth, were related to observed patterns in autumn recruitment. When deer density was low (approx. 1 deer/km2) during the 1960s, fawn/female ratios were high ranging from 1.1 to 1.4 when minimum temperatures during the prior winter averaged −16° C and −8° C, respectively. Likewise, during the 2000s, when deer density was high (approx. 3 deer/km2), fawn/female ratios ranged from 0.6 to 0.9 when minimum daily temperatures during the previous winter were −16° C and −8° C, respectively. Large‐scale Pacific‐based climatic indices (>2,000 km to the Pacific coast) were correlated with local weather and helped explain variability in autumn recruitment. Higher values of the multivariate el niño southern oscillation and Pacific decadal oscillation were correlated with warmer and drier winters in the North Dakota badlands, whereas the North Pacific Index was correlated with colder and snowy winters. The ability to predict recruitment from local weather or from broad‐scale climate indices (oscillations) provides greater opportunities for conservation and management, such as adjusting harvest quotas prior to autumn harvest. © 2015 The Wildlife Society.
Aspalathin improves glucose and lipid metabolism in 3T3‐L1 adipocytes exposed to palmitate
Authors: Mazibuko Sithandiwe E. , Joubert Elizabeth , Johnson Rabia , Louw Johan , Opoku Andrew R. , Muller Christo J. F.
Published: August 2015

Scope

Saturated‐free fatty acids, such as palmitate, are associated with insulin resistance. This study aimed to establish if an aspalathin‐enriched green rooibos extract (GRE) and, its major flavanoid, aspalathin (ASP) could contribute significantly to the amelioration of experimentally induced insulin resistance in 3T3‐L1 adipocytes.

Methods and results

3T3‐L1 adipocytes were cultured in DMEM containing 0.75 mM palmitate for 16 h to induce insulin resistance before treatment for 3 h with GRE (10 μg/mL) or ASP (10 μM). GRE and ASP reversed the palmitate‐induced insulin resistance. At a protein level GRE and ASP suppressed nuclear factor kappa beta (NF‐κB), insulin receptor substrate one (serine 307) (IRS1 (Ser 307)) and AMP‐activated protein kinase phosphorylation and increased serine/threonine kinase AKT (AKT) activation, while only GRE increased glucose transporter four (Glut4) protein expression. Peroxisome proliferator‐activated receptor alpha and gamma (PPARα and γ), and carnitine palmitoyltransferase one (CPT1) expression were increased by ASP alone.

Conclusion

Together these effects offer a plausible explanation for the ameliorative effect of GRE and ASP on insulin‐resistance, an underlying cause for obesity and type 2 diabetes.
Systematic analysis of the polyphenol metabolome using the Phenol‐Explorer database
Authors: Rothwell Joseph A. , Urpi‐Sarda Mireia , Boto‐Ordoñez Maria , Llorach Rafael , Farran‐Codina Andreu , Barupal Dinesh Kumar , Neveu Vanessa , Manach Claudine , Andres‐Lacueva Cristina , Scalbert Augustin
Published: August 2015

Scope

The Phenol‐Explorer web database details 383 polyphenol metabolites identified in human and animal biofluids from 221 publications. Here, we exploit these data to characterize and visualize the polyphenol metabolome, the set of all metabolites derived from phenolic food components.

Methods and results

Qualitative and quantitative data on 383 polyphenol metabolites as described in 424 human and animal intervention studies were systematically analyzed. Of these metabolites, 301 were identified without prior enzymatic hydrolysis of biofluids, and included glucuronide and sulfate esters, glycosides, aglycones, and O‐methyl ethers. Around one‐third of these compounds are also known as food constituents and corresponded to polyphenols absorbed without further metabolism. Many ring‐cleavage metabolites formed by gut microbiota were noted, mostly derived from hydroxycinnamates, flavanols, and flavonols. Median maximum plasma concentrations (Cmax) of all human metabolites were 0.09 and 0.32 μM when consumed from foods or dietary supplements, respectively. Median time to reach maximum plasma concentration in humans (Tmax) was 2.18 h.

Conclusion

These data show the complexity of the polyphenol metabolome and the need to take into account biotransformations to understand in vivo bioactivities and the role of dietary polyphenols in health and disease.
Sulforaphane inhibits damage‐induced poly (ADP‐ribosyl)ation via direct interaction of its cellular metabolites with PARP‐1
Authors: Piberger Ann Liza , Keil Claudia , Platz Stefanie , Rohn Sascha , Hartwig Andrea
Published: August 2015

Scope

The isothiocyanate sulforaphane, a major breakdown product of the broccoli glucosinolate glucoraphanin, has frequently been proposed to exert anticarcinogenic properties. Potential underlying mechanisms include a zinc release from Kelch‐like ECH‐associated protein 1 followed by the induction of detoxifying enzymes. This suggests that sulforaphane may also interfere with other zinc‐binding proteins, e.g. those essential for DNA repair. Therefore, we explored the impact of sulforaphane on poly (ADP‐ribose)polymerase‐1 (PARP‐1), poly (ADP‐ribosyl)ation (PARylation), and DNA single‐strand break repair (SSBR) in cell culture.

Methods and results

Immunofluorescence analyses showed that sulforaphane diminished H2O2‐induced PARylation in HeLa S3 cells starting from 15 μM despite increased lesion induction under these conditions. Subcellular experiments quantifying the damage‐induced incorporation of 32P‐ADP‐ribose by PARP‐1 displayed no direct impact of sulforaphane itself, but cellular metabolites, namely the glutathione conjugates of sulforaphane and its interconversion product erucin, reduced PARP‐1 activity concentration dependently. Interestingly, this sulforaphane metabolite‐induced PARP‐1 inhibition was prevented by thiol compounds. PARP‐1 is a stimulating factor for DNA SSBR‐rate and we further demonstrated that 25 μM sulforaphane also delayed the rejoining of H2O2‐induced DNA strand breaks, although this might be partly due to increased lesion frequencies.

Conclusion

Sulforaphane interferes with damage‐induced PARylation and SSBR, which implies a sulforaphane‐dependent impairment of genomic stability.
A generalized finite‐strain damage model for quasi‐incompressible hyperelasticity using hybrid formulation
Authors: Comellas Ester , Bellomo Facundo J. , Oller Sergio
Published: August 2015

A new generalized damage model for quasi‐incompressible hyperelasticity in a total Lagrangian finite‐strain framework is presented. A Kachanov‐like reduction factor (1 − D) is applied on the deviatoric part of the hyperelastic constitutive model. Linear and exponential softening are defined as damage evolution laws, both describable in terms of only two material parameters. The model is formulated following continuum damage mechanics theory such that it can be particularized for any hyperelastic model based on the volumetric–isochoric split of the Helmholtz free energy. However, in the present work, it has been implemented in an in‐house finite element code for neo‐Hooke and Ogden hyperelasticity. The details of the hybrid formulation used are also described. A couple of three‐dimensional examples are presented to illustrate the main characteristics of the damage model. The results obtained reproduce a wide range of softening behaviors, highlighting the versatility of the formulation proposed. The damage formulation has been developed to be used in conjunction with mixing theory in order to model the behavior of fibered biological tissues. As an example, the markedly different behaviors of the fundamental components of the rectus sheath were reproduced using the damage model, obtaining excellent correlation with the experimental results from literature. Copyright © 2015 John Wiley & Sons, Ltd.
Thermo‐mechanical and tribological properties of multi‐walled carbon nanotubes filled friction composite materials
Authors: Singh Tej , Patnaik Amar
Published: August 2015

Multi‐walled carbon nanotubes (MWCNTs) filled graphite lubricated phenolic‐based friction composites reinforced with combination of lapinus/Kevlar fibers have been fabricated and subsequently evaluated for their dynamic‐mechanical and tribological properties. The experimental results indicated that the higher MWCNT content enhances the thermal stability, whereas, lower MWCNT content enhances the thermo‐mechanical properties of the friction composites. The tribo‐performance evaluation has revealed that with the increase in MWCNT content, the friction‐fade and friction‐recovery performances are enhanced. The friction‐stability and friction‐variability coefficients are influenced by the combination of MWCNT, graphite, lapinus, and Kevlar constituents. The wear performance decreases with the increase in lapinus and MWCNT, whereas, it increases when the amount of Kevlar or graphite is increased in the composites. Wear surface morphological studies have led to the qualitative characterization of the topographical attributes and the nature of the frictional contact patches which is crucial in understanding the role of MWCNT on friction and wear mechanisms of the investigated automotive brake friction materials. POLYM. COMPOS., 38:1183–1193, 2017. © 2015 Society of Plastics Engineers
Mixed matrix membranes of Pebax1657 loaded with iron benzene‐1,3,5‐tricarboxylate for gas separation
Authors: Mosleh Samira , Mozdianfard Mohammadreza , Hemmati Mahmood , Khanbabaei Ghader
Published: August 2015

Mixed matrix membranes offer major advantages in gas separation processes due to desirable properties found in both organic and inorganic membranes. In this study, a novel mixed matrix membrane was prepared for such application by incorporating iron benzene‐1,3,5‐tricarboxylate (Fe‐BTC) into the poly(amide‐6‐b‐ethylene oxide) (Pebax1657) polymer. Membranes with various loadings of 5, 10, and 20 wt% Fe‐BTC in the polymer matrix were fabricated to investigate the effect of filler loading on the membrane performance. Membranes, prepared by solution‐casting were characterized by scanning electron microscopy, thermogravimetric analysis, Fourier transform infrared, X‐ray diffraction, and tensile test. Pure gas separation of CO2, CH4, and N2 and ideal gas selectivity of CO2/CH4 and CO2/N2 were performed and permeation tests were carried out under 4, 8, and 12 bar pressures. Results show that adding Fe‐BTC into the Pebax1657 matrix improved both permeability and selectivity of the filled membranes. For instance, 10 wt% loading of Fe‐BTC into the Pebax1657 matrix led to CO2 permeability increase of 49% as well as CO2/CH4 and CO2/N2 selectivities enhancements of about 36% and 16%, respectively. POLYM. COMPOS., 38:1363–1370, 2017. © 2015 Society of Plastics Engineers
Theoretical Study of a Diesel‐Filled Airtight Structure Unit Subjected to Shaped Charge Jet Impact
Authors: Gao Zhen‐Yu , Huang Zheng‐Xiang , Guo Min , Zu Xu‐Dong , Xiao Qiang‐Qiang , Jia Xin
Published: August 2015

Diesel composite armor has high penetration resistance and can be used in tank vehicles to improve their protective capability and increase fuel oil storage. This study provides a theoretical calculation method to investigate the interaction between a shaped charge jet and a diesel‐filled airtight structure unit. Disturbance theory can predict the part of the jet that is disturbed by diesel fuel. The lumen radius for the container was varied to study its influence on the disturbance capability. A great lumen radius is found to cause lower maximum and minimum speeds of the disturbance velocity range of the jet, as well as a narrower disturbance velocity range. The reliability of the theoretical results was validated by experiments, and the experimental data show good agreement with the theoretical results.
A Qualitative Study into Egyptian Patients' Satisfaction with Physiotherapy Management of Low Back Pain
Authors: Ali Nancy , May Stephen
Published: August 2015

Background and purpose

There is strong evidence suggesting that patient satisfaction may improve therapy outcomes independent of the treatment given. Thus the aim of this study is to explore Egyptian patients' expectations and satisfaction with physical therapy management of low back pain.

Methods

A qualitative study design involving two focus groups and 10 semi‐structured interviews; all discussions were audio recorded, transcribed verbatim and analysed using a Framework analysis approach.

Results

The five final themes were about outcome of the treatment episode, the therapist characteristics, their ability to provide patient education, the service provision and involvement in the decision‐making process.

Conclusion

The therapeutic encounter between patients and therapists in an episode of back care is complex and reflects the multidimensional nature of patient satisfaction. Participants had several criteria according to which they evaluated the quality of care and were able to determine when these criteria were met or not during physiotherapy. Copyright © 2015 John Wiley & Sons, Ltd.
Sequential unfolding of the hemolysin two‐partner secretion domain from Proteus mirabilis
Authors: Wimmer Megan R. , Woods Christopher N. , Adamczak Kyle J. , Glasgow Evan M. , Novak Walter R.P. , Grilley Daniel P. , Weaver Todd M.
Published: August 2015

Protein secretion is a major contributor to Gram‐negative bacterial virulence. Type Vb or two‐partner secretion (TPS) pathways utilize a membrane bound β‐barrel B component (TpsB) to translocate large and predominantly virulent exoproteins (TpsA) through a nucleotide independent mechanism. We focused our studies on a truncated TpsA member termed hemolysin A (HpmA265), a structurally and functionally characterized TPS domain from Proteus mirabilis. Contrary to the expectation that the TPS domain of HpmA265 would denature in a single cooperative transition, we found that the unfolding follows a sequential model with three distinct transitions linking four states. The solvent inaccessible core of HpmA265 can be divided into two different regions. The C‐proximal region contains nonpolar residues and forms a prototypical hydrophobic core as found in globular proteins. The N‐proximal region of the solvent inaccessible core, however, contains polar residues. To understand the contributions of the hydrophobic and polar interiors to overall TPS domain stability, we conducted unfolding studies on HpmA265 and site‐specific mutants of HpmA265. By correlating the effect of individual site‐specific mutations with the sequential unfolding results we were able to divide the HpmA265 TPS domain into polar core, nonpolar core, and C‐terminal subdomains. Moreover, the unfolding studies provide quantitative evidence that the folding free energy for the polar core subdomain is more favorable than for the nonpolar core and C‐terminal subdomains. This study implicates the hydrogen bonds shared among these conserved internal residues as a primary means for stabilizing the N‐proximal polar core subdomain.
Development of electron spin echo envelope modulation spectroscopy to probe the secondary structure of recombinant membrane proteins in a lipid bilayer
Authors: Zhang Rongfu , Sahu Indra D. , Gibson Kaylee R. , Muhammad Nefertiti B. , Bali Avnika P. , Comer Raven G. , Liu Lishan , Craig Andrew F. , Mccarrick Robert M. , Dabney‐Smith Carole , Sanders Charles R. , Lorigan Gary A.
Published: August 2015

Membrane proteins conduct many important biological functions essential to the survival of organisms. However, due to their inherent hydrophobic nature, it is very difficult to obtain structural information on membrane‐bound proteins using traditional biophysical techniques. We are developing a new approach to probe the secondary structure of membrane proteins using the pulsed EPR technique of Electron Spin Echo Envelope Modulation (ESEEM) Spectroscopy. This method has been successfully applied to model peptides made synthetically. However, in order for this ESEEM technique to be widely applicable to larger membrane protein systems with no size limitations, protein samples with deuterated residues need to be prepared via protein expression methods. For the first time, this study shows that the ESEEM approach can be used to probe the local secondary structure of a 2H‐labeled d8‐Val overexpressed membrane protein in a membrane mimetic environment. The membrane‐bound human KCNE1 protein was used with a known solution NMR structure to demonstrate the applicability of this methodology. Three different α‐helical regions of KCNE1 were probed: the extracellular domain (Val21), transmembrane domain (Val50), and cytoplasmic domain (Val95). These results indicated α‐helical structures in all three segments, consistent with the micelle structure of KCNE1. Furthermore, KCNE1 was incorporated into a lipid bilayer and the secondary structure of the transmembrane domain (Val50) was shown to be α‐helical in a more native‐like environment. This study extends the application of this ESEEM approach to much larger membrane protein systems that are difficult to study with X‐ray crystallography and/or NMR spectroscopy.
SANIST: a rapid mass spectrometric SACI/ESI data acquisition and elaboration platform for verifying potential candidate biomarkers
Authors: Albini Adriana , Briga Daniela , Conti Matteo , Bruno Antonino , Farioli Daniela , Canali Sara , Sogno Ilaria , D'Ambrosio Gioacchino , Consonni Paolo , Noonan Douglas M.
Published: August 2015

Rationale

Surface‐Activated Chemical Ionization/Electrospray Ionization mass spectrometry (SACI/ESI‐MS) is a technique with high sensitivity and low noise that allows accurate biomarker discovery studies. We developed a dedicated SACI/ESI software, named SANIST, for both biomarker fingerprint data acquisition and as a diagnostic tool, using prostate cancer (PCa) as the disease of interest.

Methods

Liquid chromatography (LC)/SACI/ESI‐MS technology was employed to detect a potential biomarker panel for PCa disease prediction. Serum from patients with histologically confirmed or negative prostate biopsies for PCa was employed. The biomarker data (m/z or Thompson value, retention time and extraction mass chromatogram peak area) were stored in an ascii database. SANIST software allowed identification of potential biomarkers. A Bayesian scoring algorithm developed in house allowed sample separation based on comparison with samples in the database.

Results

Biomarker candidates from the carnitine family were detected at significantly lower levels in patients showing histologically confirmed PCa. Using these biomarkers, the SANIST scoring algorithm allowed separation of patients with PCa from biopsy negative subjects with high accuracy and sensitivity.

Conclusions

SANIST was able to rapidly identify and perform a preliminary evaluation of the potential diagnostic efficiency of potential biomarkers for PCa. © 2015 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.
Improved radiocarbon analyses of modern human hair to determine the year‐of‐death by cross‐flow nanofiltered amino acids: common contaminants, implications for isotopic analysis, and recommendations
Authors: Santos Guaciara M. , De La Torre Hector A. Martinez , Boudin Mathieu , Bonafini Marco , Saverwyns Steven
Published: August 2015

Rationale

In forensic investigation, radiocarbon (14C) measurements of human tissues (i.e., nails and hair) can help determine the year‐of‐death. However, the frequent use of cosmetics can bias hair 14C results as well as stable isotope values. Evidence shows that hair exogenous impurities percolate beyond the cuticle layer, and therefore conventional pretreatments are ineffective in removing them.

Methods

We conducted isotopic analysis (14C, δ13C, δ15N and C/N) of conventionally treated and cross‐flow nanofiltered amino acid (CFNAA)‐treated samples (scalp‐ and body‐hair) from a single female subject using fingernails as a reference. The subject studied frequently applies a permanent dark‐brown dye kit to her scalp‐hair and uses other care products for daily cleansing. We also performed pyrolysis‐gas chromatography/mass spectrometry (Py‐GC/MS) analyses of CFNAA‐treated scalp‐hair to identify contaminant remnants that could possibly interfere with isotopic analyses.

Results

The conventionally treated scalp‐ and body‐hair showed 14C offsets of ~21‰ and ~9‰, respectively. These offsets confirm the contamination by petrochemicals in modern human hair. A single CFNAA extraction reduced those offsets by ~34%. No significant improvement was observed when sequential extractions were performed, as it appears that the procedure introduced some foreign contaminants. A chromatogram of the CFNAA scalp‐hair pyrolysis products showed the presence of petroleum and plant/animal compound residues, which can bias isotopic analyses.

Conclusions

We have demonstrated that CFNAA extractions can partially remove cosmetic contaminants embedded in human hair. We conclude that fingernails are still the best source of keratin protein for year‐of‐death determinations and isotopic analysis, with body‐hair and/or scalp‐hair coupled with CFNAA extraction a close second. Copyright © 2015 John Wiley & Sons, Ltd.