bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial‐dependent anticancer activity of δ‐tocotrienol and its synthetic derivatives in HER‐2/neu overexpressing breast adenocarcinoma cells
Authors: Viola Valentina , Ciffolilli Silvia , Legnaioli Silvia , Piroddi Marta , Betti Michele , Mazzini Francesco , Pierpaoli Elisa , Provinciali Mauro , Galli Francesco
Published: January 2013

Anticancer activity and mitochondrial mechanism of the vitamin E form δ‐tocotrienol (δ‐T3) was investigated in HER‐2/neu‐overexpressing human SKBR3 and murine TUBO breast cancer cells. δ‐T3 was confirmed to possess high cytotoxic and apoptotic activity in SKBR3 cells as compared with all natural forms of vitamin E and several synthetic forms that included novel derivatives with the same backbone of δ‐T3 such as δ‐tocotrienyl‐succinyl amide (δ‐T3AS) and the redox‐active analogue δ‐tocotrienyl amine (δ‐T3NH2). As observed in the case of alpha‐TOS, a prototypical anticancer drug derived from α‐tocopherol, succinylation of δ‐T3 enhanced citotoxicity and apoptotic activity of the vitamer. δ‐T3 induced apoptosis of SKBR3 cells was associated with mitochondrial destabilization, energy failure, and unbalanced activity of stress/survival MAPKs, namely p38 and ERK1/2 pathways. An increased generation of ROS followed to such a series of early events. Enhanced activity of δ‐T3 in this human carcinoma cell line was characterized by the sustained uptake and oxidative transformation to the quinone derivative δ‐T3Q, thereby suggesting redox effects in SKBR3 mitochondria by this vitamer. Viability and uptake data show a different pattern of responses in TUBO cells with higher response to synthetic derivatives of δ‐T3 than in SKBR3 cells. In conclusion, synthetic derivatives of δ‐T3 with enhanced apoptotic activity in breast carcinoma cells are investigated for the first time in this study also describing mechanistic aspects of mitochondrial effects of δ‐T3. Further investigation in preclinical models of HER2/neu‐high breast adenocarcinoma is underway to identify other and more effective forms of VE in this type of cancer. © 2013 BioFactors, 39(4):485–493, 2013
Humphrey Ridley (1653‐1708)
Authors: Veith Philip , Watanabe Koichi , Shoja Mohammadali M. , Blaak Christa , Loukas Marios , Tubbs R. Shane
Published: January 2013

Humphrey Ridley is a little known character in the history of anatomy and physiology. Born in 1653, Ridley was a physician and anatomist who followed the research done by Willis, Vieussens, and Galen. Outside of a cursory knowledge of his birth and death, readers have only two remnants of his contributions to science: The Anatomy of the Brain, containing its Mechanism and Physiology and Observationes Quaedam Medico‐Practicae et Physiologicae de Asthmate et Hydrophobia. The former text was the first book in the English language written on the human brain. Ridley's studies using cadavers executed by hanging provided him with a novel view of the venous drainage and lymphatic system not seen as accurately by those before him. Since the study of the brain was still largely in its infancy, he was not without his errors of deduction as to the purpose of parts of the brain and its pathologies. With his dissections, however, Ridley was able to build on the collective knowledge of neuroanatomy and provided new insight into brain structure and function. The current paper reviews what is known of Ridley's life and contributions to neuroanatomy and neurophysiology. Clin. Anat. 28:12–15, 2015. © 2013 Wiley Periodicals, Inc.
Drospirenone‐Containing Oral Contraceptives and Risk of Adverse Outcomes After Myocardial Infarction
Authors: Karabay Can Yucel , Kocabay Gonenc , Oduncu Vecih , Kalayci Arzu , Guler Ahmet , Karagöz Ali , Candan Ozkan , Basaran Ozcan , Zehir Regayip , İzgi Akın , Esen Ali Metin , Kırma Cevat
Published: January 2013

Background

The association between oral contraceptives (OC) and myocardial infarction remains controversial. The new generation contraceptive Yasmin (30 µg ethinyl estradiol and 3 mg drospirenone) has a lower estrogen and newer progestin component. To date, there are no data available for the myocardial infarction risk and outcome for drospirenone. We aimed to investigate the effect of Yasmin use on cardiovascular outcomes in patients with acute ST segment elevation myocardial infarction (STEMI) undergoing primary angioplasty.

Methods

We retrospectively evaluated 1851 patients who underwent primary angioplasty for acute STEMI. Of them, 440 female patients (23.8%) composed the study population and 12 female (2.7%) were taking the oral contraceptive‐Yasmin at the time of infarction. Patients were divided into two groups based on their age (≥50 (n = 339) and <50 years old). Patients under 50 years‐old (n = 101) were separated into two groups according to use of OC therapy (OC (+) group n = 12; OC (−) group n = 89).

Results

Patients who were older than 50‐year‐old were more likely to have comorbid conditions like diabetes mellitus and hypertension than other groups. Current smoking status was significantly higher in OC (+) group than OC (−) group (P = 0.007). There was a significant difference in favour of OC (+) group when compared with OC (−) group for the increased angiographic thrombus burden according to both TIMI and Yip classification (P = 0.045 and P = 0.029, respectively). The incidence of final TIMI 3 flow and post‐procedural complete ST resolution were significantly lower in OC (+) group (P = 0.019, P = 0.002, respectively). In multivariate logistic regression analysis, use of OC was found to be an independent predictor of high grade thrombus burden (OR 5.13, 95% CI 1.07–24.60, P = 0.04).

Conclusion

This is the first study to evaluate the myocardial infarction risk and its subsequent clinical sequelae in women having a STEMI while taking the OC‐Yasmin. Women on the oral contraception Yasmin, who underwent coronary revascularization had a lower post‐procedural complete ST resolution and worse left ventricular function. Furthermore, OC use with Yasmin is an independent predictor of a high‐grade thrombus burden. © 2013 Wiley Periodicals, Inc.
Dosing of iodinated contrast volume: A new simple algorithm to stratify the risk of contrast‐induced nephropathy in patients with acute coronary syndrome
Authors: Raposeiras‐Roubín Sergio , Abu‐Assi Emad , Ocaranza‐Sánchez Raymundo , Álvarez‐Álvarez Belén , Cambeiro‐González Cristina , Fandiño‐Vaquero Rubén , García‐Castelo Alberto , García‐Acuña José María , González‐Juanatey José Ramón
Published: January 2013

Objectives and background

Previous studies on contrast‐induced nephropathy (CIN) have identified contrast volume (CV) as a risk factor. The aim of our research was to define the safe dose of contrast media based on absolute CV, maximum allowable contrast dose (MACD) and estimated glomerular filtrate rate (eGFR).

Methods and Results

A total of 940 consecutive patients with acute coronary syndrome (ACS) were enrolled. Fifty‐four patients developed CIN. MACD was defined as 5*body weight/serum creatinine. When using a CV higher than MACD, CIN‐risk was increased 19‐fold (OR 9.810–39.307, P < 0.001). For the CV/eGFR ratio, we found that for every increase of one‐tenth, CIN‐risk increased by 4.9% (OR 1.037–1.061, P < 0.001). The discriminative ability of CV (C statistic = 0.626 ± 0.038) was significantly lower than for the CV/MACD (C statistic = 0.782 ± 0.036, P = 0.003) and CV/eGFR (C statistics: 0.796 ± 0.033 for MDRD‐4, 0.796 ± 0.034 for Cockcroft‐Gault, and 0.803 ± 0.033 for CKD‐EPI; P < 0.001). There were no differences in the discriminative ability to predict CIN between the three eGFR equations. The combination of CV/MACD and CV/eGFR in a single protocol increases the positive predictive value of the Mehran risk score (40.7% vs. 8.8%) with the same sensitivity (90.7% vs. 83.3%). High doses of relative CV (CV/MACD and CV/eGFR) were also significantly associated with higher in‐hospital mortality, reinfarction, and heart failure.

Conclusions

A sequential protocol based on CV/MACD and CV/eGFR appropriately identified those ACS patients who developed CIN, with predictive values similar to a Mehran score, reducing the false positive rate. It is also useful to predict risk of in‐hospital cardiac events regardless of GRACE score. © 2013 Wiley Periodicals, Inc.
Selective Monoacylation of Diols by Substrate Assisted Catalysis in T40A Candida antarctica Lipase B
Authors: Hamberg Anders , Magnusson Anders O. , Hu Francis J. , Hult Karl
Published: January 2013

The selectivity towards diols over monoesters in the esterification of diols catalysed by lipase B from Candida antarctica (CALB) was improved by the single point mutation T40A in the enzyme’s oxyanion hole. Substrate‐assisted catalysis was suggested from molecular modelling of the tetrahedral intermediate in esterification of 1,2‐ethanediol catalysed by T40A CALB. The non‐reacting hydroxyl group of the diol forms a hydrogen bond to the oxyanion in the transition state, replacing that deleted in mutation. Monoester yields in transacylation reactions were monitored over time to compare the selectivities for wild‐type and T40A CALB. The results showed increased selectivities towards the diols tested over their corresponding monoesters as a result of the T40A mutation with substrate‐assisted catalysis as a plausible explanation.
A New Family of Trinuclear Nickel(II) Complexes as Single‐Molecule Magnets
Authors: Biswas Rituparna , Ida Yumi , Baker Michael L. , Biswas Saptarshi , Kar Paramita , Nojiri Hiroyuki , Ishida Takayuki , Ghosh Ashutosh
Published: January 2013

Three new trinuclear nickel (II) complexes with the general composition [Ni3L3(OH)(X)](ClO4) have been prepared in which X=Cl− (1), OCN− (2), or N3− (3) and HL is the tridentate N,N,O donor Schiff base ligand 2‐[(3‐dimethylaminopropylimino)methyl]phenol. Single‐crystal structural analyses revealed that all three complexes have a similar Ni3 core motif with three different types of bridging, namely phenoxido (μ2 and μ3), hydroxido (μ3), and μ2‐Cl (1), μ1,1‐NCO (2), or μ1,1‐N3 (3). The nickel(II) ions adopt a compressed octahedron geometry. Single‐crystal magnetization measurements on complex 1 revealed that the pseudo‐three‐fold axis of Ni3 corresponds to a magnetic easy axis, being consistent with the magnetic anisotropy expected from the coordination structure of each nickel ion. Temperature‐dependent magnetic measurements indicated ferromagnetic coupling leading to an S=3 ground state with 2J/k=17, 17, and 28 K for 1, 2, and 3, respectively, with the nickel atoms in an approximate equilateral triangle. The high‐frequency EPR spectra in combination with spin Hamiltonian simulations that include zero‐field splitting parameters DNi/k=−5, −4, and −4 K for 1, 2, and 3, respectively, reproduced the EPR spectra well after a anisotropic exchange term was introduced. Anisotropic exchange was identified as Di,j/k=−0.9, −0.8, and −0.8 K for 1, 2, and 3, respectively, whereas no evidence of single‐ion rhombic anisotropy was observed spectroscopically. Slow relaxation of the magnetization at low temperatures is evident from the frequency‐dependence of the out‐of‐phase ac susceptibilities. Pulsed‐field magnetization recorded at 0.5 K shows clear steps in the hysteresis loop at 0.5–1 T, which has been assigned to quantum tunneling, and is characteristic of single‐molecule magnets.
Reaction of N‐Heterocyclic Silylenes with Thioketone: Formation of Silicon–Sulfur Three (Si‐C‐S)‐ and Five (Si‐C‐C‐C‐S)‐Membered Ring Systems
Authors: Azhakar Ramachandran , Ghadwal Rajendra S. , Roesky Herbert W. , Mata Ricardo A. , Wolf Hilke , Herbst‐Irmer Regine , Stalke Dietmar
Published: January 2013

Three‐ and five‐membered rings that bear the (Si‐C‐S) and (Si‐C‐C‐C‐S) unit have been synthesized by the reactions of LSiCl (1; L=PhC(NtBu)2) and L′Si (2; L′=CH{(CCH2)(CMe)(2,6‐iPr2C6H3N)2}) with the thioketone 4,4′‐bis(dimethylamino)thiobenzophenone. Treatment of 4,4′‐bis(dimethylamino)thiobenzophenone with LSiCl at room temperature furnished the [1+2]‐cycloaddition product silathiacyclopropane 3. However, reaction of 4,4′‐bis(dimethylamino)thiobenzophenone with L′Si at low temperature afforded a [1+4]‐cycloaddition to yield the five‐membered ring product 4. Compounds 3 and 4 were characterized by NMR spectroscopy, EIMS, and elemental analysis. The molecular structures of 3 and 4 were unambiguously established by single‐crystal X‐ray structural analysis. The room‐temperature reaction of 4,4′‐bis(dimethylamino)thiobenzophenone with L′Si resulted in products 4 and 5, in which 4 is the dearomatized product and 5 is formed under the 1,3‐migration of a hydrogen atom from the aromatic phenyl ring to the carbon atom of the CS unit. Furthermore, the optimized structures of probable products were investigated by using DFT calculations.
Understanding the Electronic Structures of Graphene Quantum Dot Physisorption and Chemisorption onto the TiO2 (110) Surface: A First‐Principles Calculation
Authors: Long Run
Published: January 2013

We investigated the interfacial electronic structure and charge transfer properties of graphene quantum dot (GQD) physisorption and chemisorption on the TiO2 (110) surface from density functional theory calculations. The simulations show that a slight charge transfer occurs in physisorption case while a significant charge transfer takes place in chemisorption configuration. We present a detailed comparison of the similarities and differences between the electronic structures. The similarities originate from the positive work function difference in both the physisorption and chemisorption configurations, which is able to drive electron transfer from GQD into TiO2, leading to charge separation across the GQD–TiO2 interface. The differences stem from the interaction between the GQD and TiO2 substrate. For example, GQD bounds to TiO2 surface through van der Waals interactions in the case of physisorption. In the chemisorption configuration, however, there exists strong covalent bonding between them. This leads to much more efficient charge separation for chemisorption than for physisorption. Furthermore, the GQD–TiO2 composites show large band‐gap narrowing that could extend the optical absorption edge into the visible‐light region. This should imply that chemisorbed GQDs produce a composite with better photocatalytic and photovoltaic performance than composites formed through physisorption.
Prenatal Exposures Associated with Neurodevelopmental Delay and Disabilities
Authors: Diav‐Citrin Orna
Published: January 2013

Neurobehavioral teratology refers to the study of the abnormal development of the structure and the behavioral functions of the central nervous system, which result from exposure to exogenous agents during prenatal development. The focus of this review is the effects of various prenatal exposures on human neurodevelopment. Studies that deal with the adverse effects of infectious agents (rubella, cytomegalovirus, and toxoplasma), teratogenic drugs (e.g., antiepileptic drugs such as phenytoin, valproate, and carbamazepine, coumarin derivatives, and retinoids), alcohol, and other substances of abuse will be reviewed. Additionally, prenatal exposure to industrial or environmental chemicals (e.g., lead, methylmercury, and polycarbonated biphenyls) as well as exposure of the embryo or fetus to high amounts of ionizing radiation will be addressed. Possible mechanisms of selected neurobehavioral teratogens will also be discussed. © 2013 Wiley Periodicals, Inc. Dev Disabil Res Rev 2011;17:71–84.
Cerebral Palsy—Don't Delay
Authors: McIntyre Sarah , Morgan Cathy , Walker Karen , Novak Iona
Published: January 2013

Cerebral palsy (CP) is the most severe physical disability within the spectrum of developmental delay. CP is an umbrella term describing a group of motor disorders, accompanied by many associated impairments. The disability is a result of injuries to the developing brain occurring any time from the first trimester of pregnancy through to early childhood. However, for the great majority, their full etiological causal pathway remains unclear. It is important to discriminate as early as possible between: (a) mild or nonspecific motor delay, (b) developmental coordination disorder, (c) syndromes, (d) metabolic and progressive conditions, and (e) CP with its various motor types and distributions. The most promising predictive tool for CP is the general movements assessment, which assesses the quality of spontaneous movements of infants in the first 4 months of life. We propose a change in diagnostic practice. We recommend a shift away from referral for intervention following a formal (most often late) description of CP, to one of referral for intervention whichoccurs immediately once an infant is considered “at risk” of CP. © 2013 Wiley Periodicals, Inc. Dev Disabil Res Rev 2011;17:114–129.
Differentiating Autism Spectrum Disorder From Other Developmental Delays In The First Two Years Of Life
Authors: Mitchell Shelley , Cardy Janis Oram , Zwaigenbaum Lonnie
Published: January 2013

Advances in the identification of the early signs of autism spectrum disorder (ASD) have occurred despite the heterogeneity of the disorder and its variable onset and presentation. Using various methodologies including retrospective studies, community samples, and sibling cohorts, researchers have identified behavioral markers of the disorder that emerge over the first 2 years of life. However, there are characteristics of ASD that overlap with other types of developmental delay (DD), which may complicate differential diagnosis in young children. A review of the literature was conducted to identify the most promising behavioral markers that distinguish ASD from other types of DD in the first 2 years of life. The review identified profiles of behavioral markers in the social realm by 12 months and in the communication realm by 18 months, which along with additional atypical motor behaviors could distinguish ASD from DD. This constellation of features coupled with a flat or declining trajectory in specific aspects of social and communication development, may assist clinicians in targeting early interventions to at‐risk infants. © 2013 Wiley Periodicals, Inc. Dev Disabil Res Rev 2011;17:130–140.
Cell‐autonomous sex determination outside of the gonad
Authors: Arnold Arthur P. , Chen Xuqi , Link Jenny C. , Itoh Yuichiro , Reue Karen
Published: January 2013

Background: The classic model of sex determination in mammals states that the sex of the individual is determined by the type of gonad that develops, which in turn determines the gonadal hormonal milieu that creates sex differences outside of the gonads. However, XX and XY cells are intrinsically different because of the cell‐autonomous sex‐biasing action of X and Y genes. Results: Recent studies of mice, in which sex chromosome complement is independent of gonadal sex, reveal that sex chromosome complement has strong effects contributing to sex differences in phenotypes such as metabolism. Adult mice with two X chromosomes (relative to mice with one X chromosome) show dramatically greater increases in body weight and adiposity after gonadectomy, irrespective of their gonadal sex. When fed a high‐fat diet, XX mice develop striking hyperinsulinemia and fatty liver, relative to XY mice. The sex chromosome effects are modulated by the presence of gonadal hormones, indicating an interaction of the sex‐biasing effects of gonadal hormones and sex chromosome genes. Conclusions: Other cell‐autonomous sex chromosome effects are detected in mice in many phenotypes. Birds (relative to eutherian mammals) are expected to show more widespread cell‐autonomous sex determination in non‐gonadal tissues, because of ineffective sex chromosome dosage compensation mechanisms. Developmental Dynamics 242:371–379, 2013. © 2013 Wiley Periodicals, Inc.
Loss of cell‐extracellular matrix interaction triggers retinal regeneration accompanied by Rax and Pax6 Activation
Authors: Nabeshima Ayaka , Nishibayashi Chisato , Ueda Yoko , Ogino Hajime , Araki Masasuke
Published: January 2013

The whole retina regenerates from retinal pigmented epithelial (RPE) cells by transdifferentiation in the adult newt and Xenopus laevis when it is surgically removed. We produced a transgenic animal line, in which EGFP expression is under the control of Rax pomotor. Using F1 and F2 generations, we analyzed Rax‐EGFP expression during retinal regeneration in a tissue culture model. In the culture, 4 zones were distinguished as RPE cells migrating outwards from the periphery of the explant: the explant zone, epithelial zone, transition zone and differentiation zone. Expression of transcription factors such as Pax6 and Rax‐EGFP was observed in different zones. Rax‐EGFP expression preceded Pax6 expression, and the expression of both genes occurred in RPE cells that had lost contact with the basement membrane facing the choroid. We have developed a new culture method in which RPE tissues are embedded in Matrigel. This method has many advantages over the previous gel‐overlay method to reproduce construction of 3D‐retinal structures and clearly showed that RPE cells need to be detached from the choroid before entering the regeneration pathway. The present results indicate that the temporal changes in cell‐cell and cell‐extracellular matrix interactions regulate transdifferentiation. genesis 51:410–419. © 2013 Wiley Periodicals, Inc.
The influence of the UV irradiation on degradation of virgin rapeseed oils
Authors: Pawłowicz Roman , Gromadzka Justyna , Tynek Maria , Tylingo Robert , Wardencki Waldemar , Karlovits Gyorgy
Published: January 2013

This paper presents research which is a continuation of the investigations described earlier. The aim of these studies was to determine the influence of UV irradiation on flavor and the oxidative stability of different rapeseed oils varieties. For the purpose of this study, oil samples underwent accelerated deterioration for 4.5 h under a UV light test. In the obtained sample, characteristic values (peroxide (PV, 1.23–1.62 meq O2/kg), anisidine (AnV, 0.53–1.20) and TOTOX (3.02–4.14)), concentration of conjugated dienes ($E_{1\,{\rm cm}}^{{\rm 1}\% } $ at 232 nm 1.21–2.08) and trienes ($E_{1\,{\rm cm}}^{{\rm 1}\% } $ at 268 nm 0.11–0.34), carotenoids and chlorophylls, oxidative stability (DSC‐test), volatiles were determined and a sensory evaluation was carried out. Changes in the PV and AnV values in the function of irradiation time have fluctuating character (e.g., for PV from 0.45 meq O2/kg before UV treatment to 1.61 meq O2/kg after 4.5 h of the UV irradiation and for AnV from 0 to 1.20), therefore they cannot be used as quality indicators. There was no correlation between these values and the level of generated sensory descriptors and the sum of volatiles as well as the initial oils stability (DSC‐test). During UV irradiation, the decrease in carotene and chlorophyll content had a linear pattern. The absolute losses of carotenoids were from 1 ppm (samples 5 and 6) to 3.8 ppm (sample 2) and for chlorophylls from 0.02 ppm (sample 5) to 0.25 ppm (sample 4). There was a high correlation (R2 = 0.87) observed between the maximum intensity of the varnish descriptor and IP‐DSC of the virgin oils for all samples.
Enzymatic hydrolysis of palm stearin to produce diacylglycerol with a highly thermostable lipase
Authors: Xu Yang , Guo Shaohua , Wang Weifei , Wang Yonghua , Yang Bo
Published: January 2013

This paper for the first time presents the production of diacylglycerol (DAG) by hydrolysis of high‐melting oil by a highly thermostable lipase (T1 lipase). T1 lipase was expressed in recombinant Escherichia coli, and used to produce DAG by catalyzing the hydrolysis of palm stearin. The optimal conditions were obtained by a water content of 30% w/w (with respect to oil mass), T1 lipase at a concentration of 7.5 U/g (U/w, with respect to oil mass) and at 60°C. Scale‐up reaction was attempted based on the optimized conditions and 28.1% of DAG was achieved. Molecular distillation was employed for purification of DAG from the reaction mixture and the final DAG product yielded 42.5% of DAG (27.8% for 1,3‐DAG and 14.7% for 1,2‐DAG) and 57.5% of triacylglycerol (TAG). During hydrolysis, T1 lipase was discovered to show 1,3‐regiospecific activity toward TAGs. The results indicated that T1 lipase is a prospective enzyme which can be used in the modification of high‐melting oils and fats.

Practical applications: Enzymatic modification of high‐melting oils is a challenging task. Here DAG production by T1 lipase‐catalyzed hydrolysis of palm stearin (PS) is reported for the first time.
Binding and Fluorescent Sensing of Dicarboxylates by a Bis(calix[4]pyrrole)‐Substituted BODIPY Dye
Authors: Gotor Raúl , Costero Ana M. , Gaviña Pablo , Gil Salvador , Parra Margarita
Published: January 2013

A bis(calix[4]pyrrole)‐substituted BODIPY ditopic receptor 1 has been synthesised and characterised. The binding and sensing properties of 1 towards several aliphatic and aromatic dicarboxylates have been evaluated by using UV/Vis fluorescence and 1H NMR spectroscopy. The receptor strongly binds linear α,ω‐dicarboxylates of appropriate lengths (C9 and C10) by acting as a cleft. For all dicarboxylates, the binding event is detected by a bathochromic shift in the UV/Vis spectra of the receptor and by strong quenching of its fluorescence.
A method to predict and understand fish survival under dynamic chemical stress using standard ecotoxicity data
Authors: Ashauer Roman , Thorbek Pernille , Warinton Jacqui S. , Wheeler James R. , Maund Steve
Published: January 2013

The authors present a method to predict fish survival under exposure to fluctuating concentrations and repeated pulses of a chemical stressor. The method is based on toxicokinetic-toxicodynamic modeling using the general unified threshold model of survival (GUTS) and calibrated using raw data from standard fish acute toxicity tests. The model was validated by predicting fry survival in a fish early life stage test. Application of the model was demonstrated by using Forum for Co-ordination of Pesticide Fate Models and Their Use surface water (FOCUS-SW) exposure patterns as model input and predicting the survival of fish over 485 d. Exposure patterns were also multiplied by factors of five and 10 to achieve higher exposure concentrations for fish survival predictions. Furthermore, the authors quantified how far the exposure profiles were below the onset of mortality by finding the corresponding exposure multiplication factor for each scenario. The authors calculated organism recovery times as additional characteristic of toxicity as well as number of peaks, interval length between peaks, and mean duration as additional characteristics of the exposure pattern. The authors also calculated which of the exposure patterns had the smallest and largest inherent potential toxicity. Sensitivity of the model to parameter changes depends on the exposure pattern and differs between GUTS individual tolerance and GUTS stochastic death. Possible uses of the additional information gained from modeling to inform risk assessment are discussed. Environ. Toxicol. Chem. 2013;32:954–965. © 2013 SETAC
INVESTIGATION OF THE TOXICOKINETICS OF PETROLEUM HYDROCARBON DISTILLATES WITH THE EARTHWORM EISENIA ANDREI
Authors: Cermak Janet , Stephenson Gladys , Birkholz Detlef , Dixon D. George
Published: January 2013

The Canada-wide standards for petroleum hydrocarbons in soils regulate petroleum hydrocarbons based on four distillate ranges: F1 (C6–C10), F2 (>C10–C16), F3 (>C16–C34), and F4 (>C34). Previous toxicity tests with earthworms and F2, as well as two subfractions of F3, F3a (>C16–C23) and F3a (>C23–C34), indicate that test durations might not be sufficiently long to reach threshold effect concentrations, likely because of the differing toxicokinetics for each distillate. A study was conducted to determine the toxicokinetics of both aliphatic and aromatic fractions of F2, F3a, and F3b with the earthworm Eisenia andrei. Peak accumulation curves were observed for F2 aliphatics and aromatics and F3a aromatics, likely as a result of changes in exposure concentration over the test duration via loss or a decrease in the bioavailable fraction. Biota–soil accumulation factors were >1 for total F2 aliphatics and aromatics and F3a aromatics as well as for several individual polyaromatic hydrocarbons for each distillate. Aromatics were disproportionately accumulated over aliphatics and were the main contributors to toxicity; therefore, aromatics and aliphatics should be regulated separately. The toxicokinetics were used to interpret previous toxicity data. Higher molecular weight distillates need longer-than-standard test durations to determine toxicity, so toxicity test results from fixed, standard-duration tests are not strictly comparable for these petroleum distillates. Environ. Toxicol. Chem. 2013;32:1006–1015. © 2013 SETAC
Breakpoint characterization of the der(19)t(11;19)(q13;p13) in the ovarian cancer cell line SKOV‐3
Authors: Onkes Wiebke , Fredrik Regina , Micci Francesca , Schönbeck Benjamin J , Martin‐Subero Jose I , Ullmann Reinhard , Hilpert Felix , Bräutigam Karen , Janssen Ottmar , Maass Nicolai , Siebert Reiner , Heim Sverre , Arnold Norbert , Weimer Jörg
Published: January 2013

About 20% of ovarian carcinomas show alterations of 19p13 and/or 19q13 in the form of added extra material whose origin often is from chromosome 11. Based on earlier spectral karyotype analysis of the ovarian cancer cell line SKOV‐3, which shows an unbalanced translocation der(19)t(11;19), the aim of this study was to determine the precise breakpoints of that derivative chromosome. After rough delimitation of the breakpoints of microdissected derivative chromosomes by array analysis, we designed a matrix of primers spanning 11q13.2 and 19p13.2 detecting multiple amplicons on genomic and cDNA. Sequencing the amplicons, accurate localization of both breakpoints on both chromosomes was possible and we found that exon 14 of HOOK2 from chromosome 19 and exon 2 of ACTN3 from chromosome 11 were fused in the derivative chromosome. The breakpoint in the HOOK2 gene was in an intrinsic triplet of nucleic acids leading to a shift in the ACTN3 reading frame in the derivative chromosome. This frameshift alteration should give rise to an early stop codon causing a loss of function of ACTN3. Signals in two‐dimensional Western blotting exactly match to calculated molecular mass and the isoelectric point of the fusion protein. © 2013 Wiley Periodicals, Inc.
Increased miR‐195 aggravates neuropathic pain by inhibiting autophagy following peripheral nerve injury
Authors: Shi Guodong , Shi Jiangang , Liu Kun , Liu Ning , Wang Yuan , Fu Zhiyi , Ding Jiandong , Jia Lianshun , Yuan Wen
Published: January 2013

Following peripheral nerve injury (PNI) microglia proliferates and adopts inflammation that contributes to development and maintenance of neuropathic pain. miRNAs and autophagy are two important factors in the regulation of inflammation. However, little is known about whether miRNAs regulate neuroinflammation and neuropathic pain by controlling autophagy. In the study, we demonstrated that miR‐195 levels were markedly increased in rats subjected to L5 spinal nerve ligation (SNL). Upregulated miR‐195 was also found in spinal microglia of rats with SNL. The overexpression of miR‐195 contributed to lipopolysaccharide‐induced expression of proinflammatory cytokines IL‐1β, TNF‐α, and iNOS in cultured microglia. Upregulated miR‐195 also resulted in increased mechanical and cold hypersensitivity after PNI, whereas miR‐195 inhibition reduced mechanical and cold sensitivity. We further demonstrated that PNI significantly inhibited microglial autophagy activation, whereas miR‐195 inhibitor treatment increased autophagy activation and suppressed neuroinflammation in vivo and in vitro. More important, autophagy inhibition impaired miR‐195 inhibitor‐induced downregulation of neuroinflammation and neuropathic pain. Additionally, ATG14 was identified as the functional target of miR‐195. Conclusions: These data demonstrated that miR‐195/autophagy signaling represents a novel pathway regulating neuroinflammation and neuropathic pain, thus offering a new target for therapy of neuropathic pain.
Stigmatizing attitudes toward mental illness among racial/ethnic older adults in primary care
Authors: Jimenez Daniel E. , Bartels Stephen J. , Cardenas Veronica , Alegría Margarita
Published: January 2013

Objective

The current study applies the perceived stigma framework to identify differences in attitudes toward mental health and mental health treatment among various racial/ethnic minority older adults with common mental health problems including depression, anxiety disorders, or at‐risk alcohol use. Specifically, this study examines to what extent race/ethnicity is associated with differences in (1) perceived stigma of mental illness and (2) perceived stigma for different mental health treatment options.

Methods

Analyses were conducted using baseline data collected from participants who completed the SAMHSA Mental Health and Alcohol Abuse Stigma Assessment, developed for the PRISM‐E (Primary Care Research in Substance Abuse and Mental Health for the Elderly) study, a multisite randomized trial for older adults (65+ years) with depression, anxiety, or at‐risk alcohol consumption. The final sample consisted of 1247 non‐Latino Whites, 536 African‐Americans, 112 Asian‐Americans, and 303 Latinos.

Results

African‐Americans and Latinos expressed greater comfort in speaking to primary care physicians or mental health professionals concerning mental illness compared with non‐Latino Whites. Asian‐Americans and Latinos expressed greater shame and embarrassment about having a mental illness than non‐Latino Whites. Asian‐Americans expressed greater difficulty in seeking or engaging in mental health treatment.

Conclusions

Racial/ethnic differences exist among older adults with mental illness with respect to stigmatizing attitudes toward mental illness and mental health treatment. Results of this study could help researchers and clinicians educate racial/ethnic minority older adults about mental illness and engage them in much needed mental health services. Copyright © 2013 John Wiley & Sons, Ltd.
Mapping white matter integrity in elderly people with HIV
Authors: Nir Talia M. , Jahanshad Neda , Busovaca Edgar , Wendelken Lauren , Nicolas Krista , Thompson Paul M. , Valcour Victor G.
Published: January 2013

People with HIV are living longer as combination antiretroviral therapy (cART) becomes more widely available. However, even when plasma viral load is reduced to untraceable levels, chronic HIV infection is associated with neurological deficits and brain atrophy beyond that of normal aging. HIV is often marked by cortical and subcortical atrophy, but the integrity of the brain's white matter (WM) pathways also progressively declines. Few studies focus on older cohorts where normal aging may be compounded with HIV infection to influence deficit patterns. In this relatively large diffusion tensor imaging (DTI) study, we investigated abnormalities in WM fiber integrity in 56 HIV+ adults with access to cART (mean age: 63.9 ± 3.7 years), compared to 31 matched healthy controls (65.4 ± 2.2 years). Statistical 3D maps revealed the independent effects of HIV diagnosis and age on fractional anisotropy (FA) and diffusivity, but we did not find any evidence for an age by diagnosis interaction in our current sample. Compared to healthy controls, HIV patients showed pervasive FA decreases and diffusivity increases throughout WM. We also assessed neuropsychological (NP) summary z‐score associations. In both patients and controls, fiber integrity measures were associated with NP summary scores. The greatest differences were detected in the corpus callosum and in the projection fibers of the corona radiata. These deficits are consistent with published NP deficits and cortical atrophy patterns in elderly people with HIV. Hum Brain Mapp 35:975–992, 2014. © 2013 Wiley Periodicals, Inc.
The BTBD9 gene may be associated with antipsychotic‐induced restless legs syndrome in schizophrenia
Authors: Kang Seung‐Gul , Lee Heon‐Jeong , Park Young‐Min , Yang Hee Jung , Song Hyun Mi , Lee Yu Jin , Cho Seong‐Jin , Cho Sung Nam , Kim Leen
Published: January 2013

Objective

A genome‐wide association study and several replication studies have shown significant association between BTBD9 gene single nucleotide polymorphisms and restless legs syndrome (RLS). The aim of this study is to investigate the association between the BTBD9 gene polymorphisms and antipsychotic‐induced RLS in schizophrenic patients.

Methods

Restless legs syndrome symptoms were evaluated using the diagnostic criteria of the International Restless Legs Syndrome Study Group in 190 Korean schizophrenic patients. We genotyped the rs9357271 and rs3923809 polymorphisms of the BTBD9 gene in schizophrenic patients with (n = 96) and without (n = 94) RLS symptoms.

Results

There was a significant difference in the allele frequency (χ2 = 8.14, p = 0.004) of the rs9357271 polymorphism between schizophrenic patients with and without RLS symptoms. Significant genotypic association of this single nucleotide polymorphisms with RLS symptoms was also observed for the dominant model (χ2 = 10.32, p = 0.001) and heterozygous model (χ2 = 10.9, p = 0.001). When we compared the frequencies of the rs3923809–rs9357271 haplotypes between the two groups, the overall haplotype frequencies were significantly different (permuted p = 0.037), and the A‐T haplotype was significantly more frequent in the RLS symptom group than in the no RLS symptom group (0.112 vs. 0.041, permuted p = 0.007).

Conclusions

These data suggest that the BTBD9 gene is associated with antipsychotic‐induced RLS symptoms in schizophrenic patients. Copyright © 2013 John Wiley & Sons, Ltd.
Trends in the incidence of cancer in the black population of Harare, Zimbabwe 1991–2010
Authors: Chokunonga E. , Borok M.Z. , Chirenje Z.M. , Nyakabau A.M. , Parkin D.M.
Published: January 2013

Incidence rates of different cancers have been calculated for the black population of Harare, Zimbabwe for a 20‐year period (1991–2010) coinciding with continuing social and lifestyle changes, and the peak, and subsequent wane, of the HIV‐AIDS epidemic. The overall risk of cancer increased during the period in both sexes, with rates of cervix and prostate cancers showing particularly dramatic increases (3.3% and 6.4% annually, respectively). By 2004, prostate cancer had become the most common cancer of men. The incidence of cancer of the esophagus, formerly the most common cancer of men, has remained relatively constant, whereas rates of breast and cervix cancers, the most common malignancies of women, have shown significant increases (4.9% and 3.3% annually, respectively). The incidence of Kaposi sarcoma increased to a maximum around 1998–2000 and then declined in all age groups, and in both sexes The incidence of squamous cell cancers of the conjunctiva is relatively high, with temporal trends similar to those of Kaposi sarcoma. Non‐Hodgkin lymphoma, the fifth most common cancer of men and fourth of women, showed a steady increase in incidence throughout the period (6.7–6.9% annually), although rates in young adults (15–39) have decreased since 2001. Cancer control in Zimbabwe, as elsewhere in sub‐Saharan Africa, involves meeting the challenge of emerging cancers associated with westernization of lifestyles (large bowel, breast and prostate), while the incidence of cancers associated with poverty and infection (liver, cervix and esophagus) shows little decline, and the residual burden of the AIDS‐associated cancers remains significant.
EBV counteracts IL‐21‐induced apoptosis in an EBV‐positive diffuse large B‐cell lymphoma cell line
Authors: Wu Liang , Ehlin‐Henriksson Barbro , Zhu Hong , Ernberg Ingemar , Klein George
Published: January 2013

Previously, interleukin (IL)‐21 has been found to induce apoptosis by activating the signal transducer and activator of transcription 3 (STAT3) and concomitant upregulation of c‐Myc in diffuse large B‐cell lymphoma (DLBCL) lines with unknown Epstein–Barr virus (EBV) status. Here, as a first approach toward the characterization of the role of EBV in DLCBL, the EBV gene expression and the IL‐21 sensitivity of the EBV‐positive DLBCL line, Farage, have been examined. It was found that, surprisingly, despite c‐Myc upregulation, IL‐21 induced cell proliferation rather than apoptosis in Farage. Expression of a dominant‐negative EBNA1 mutant and the consecutive downregulation of EBV gene expression antagonized the IL‐21‐induced proliferation of Farage and increased apoptosis. These findings reveal a previously unknown role of EBV in DLBCL that is of possible relevance for the current attempt to use IL‐21 in therapy.
Chemotherapy‐induced immunogenic modulation of tumor cells enhances killing by cytotoxic T lymphocytes and is distinct from immunogenic cell death
Authors: Hodge James W. , Garnett Charlie T. , Farsaci Benedetto , Palena Claudia , Tsang Kwong‐Yok , Ferrone Soldano , Gameiro Sofia R.
Published: January 2013

Certain chemotherapeutic regimens trigger cancer cell death while inducing dendritic cell maturation and subsequent immune responses. However, chemotherapy‐induced immunogenic cell death (ICD) has thus far been restricted to select agents. In contrast, several chemotherapeutic drugs modulate antitumor immune responses, despite not inducing classic ICD. In addition, in many cases tumor cells do not die after treatment. Here, using docetaxel, one of the most widely used cancer chemotherapeutic agents, as a model, we examined phenotypic and functional consequences of tumor cells that do not die from ICD. Docetaxel treatment of tumor cells did not induce ATP or high‐mobility group box 1 (HMGB1) secretion, or cell death. However, calreticulin (CRT) exposure was observed in all cell lines examined after chemotherapy treatment. Killing by carcinoembryonic antigen (CEA), MUC‐1, or PSA‐specific CD8+ CTLs was significantly enhanced after docetaxel treatment. This killing was associated with increases in components of antigen‐processing machinery, and mediated largely by CRT membrane translocation, as determined by functional knockdown of CRT, PERK, or CRT‐blocking peptide. A docetaxel‐resistant cell line was selected (MDR‐1+, CD133+) by continuous exposure to docetaxel. These cells, while resistant to direct cytostatic effects of docetaxel, were not resistant to the chemomodulatory effects that resulted in enhancement of CTL killing. Here, we provide an operational definition of “immunogenic modulation,” where exposure of tumor cells to nonlethal/sublethal doses of chemotherapy alters tumor phenotype to render the tumor more sensitive to CTL killing. These observations are distinct and complementary to ICD and highlight a mechanism whereby chemotherapy can be used in combination with immunotherapy.
INFLUENCE OF CROP SPATIAL VARIABILITY WHEN CALCULATING IRRIGATION NETWORK FLOWS
Authors: Monserrat J. , Ezpeleta M. , Colomer M.A. , Cots LL. , Barragan J.
Published: January 2013

In on‐demand irrigation network design, calculation of pipe flows is usually based on the mean water requirements of the crops that can be expected to be planted in the area. However, while the network is sized for mean water needs, the actual requirements of each plot will depend on the crop planted and may well be different from the calculated mean water needs. As a result, the network may be undersized in terms of covering the flow demands of certain of its sections.

The aim of this work was to study the influence of the spatial variability of crops on network flows and to make recommendations for methods of calculation capable of providing more reliable values for these flows.

An equation was obtained that made it possible to determine what is known as the operation quality (OQ) based on the section number and the coefficient of variation of the water needs of the crops planned for the area. This equation was applied to two networks with different plot sizes and the results were compared with others obtained when the mean water requirements were assumed. Copyright © 2013 John Wiley & Sons, Ltd.
Synthesis of multifunctional bioresponsive polymers for the management of chronic wounds
Authors: Nyanhongo Gibson S. , Sygmund Christoph , Ludwig Roland , Prasetyo Endry Nugroho , Guebitz Georg M
Published: January 2013

Novel multifunctional bioresponsive gelatin and alginate based hydrogels with in‐built antioxidant regenerating system and antimicrobial properties were successfully synthesized. These hydrogels are based on the versatile reactions catalyzed by cellobiose dehydrogenase (CDH). CDH uses cellobiose and cello‐oligosacharides as electron donors to reduce oxidized phenolic antioxidants, quinones, or molecular oxygen to H2O2 (a well‐known antimicrobial agent). The antioxidant regenerating system consisting of CDH and cellobiose increased the ability of catechol to quench nitric oxide (NO), superoxide (O2−) and hydroxyl radicals (OH•) in solution and when incorporated into hydrogels. The CDH loaded into the hydrogels free of oxidized phenolic antioxidants and quinones reduced molecular to H2O2 resulting in the complete inhibition of the growth of Stapylococcus aeureus, Bacillus subtilis, Pseudomonas putida, Escherichia coli and Cellulomonasmicrobium cellulans. This study therefore presents a new concept for synthesizing multifunctional bioresponsive chronic wound dressing polymers with in‐built continuous antioxidant system able to continuously quench [reactive oxygen species (ROS) and reactive nitrogen species (RNOS)], and antimicrobial properties able to prevent microbial colonization of wound. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.
Dynamic perfusion bioreactor system for 3D culture of rat bone marrow mesenchymal stem cells on nanohydroxyapatite/polyamide 66 scaffoldin vitro
Authors: Qian Xu , Yuan Fang , Zhimin Zhu , Anchun Mo
Published: January 2013

The aim of the study was to investigate the biocompatibility and osteogenic effectiveness of the porous nanohydroxyapatite/polyamide 66 (n‐HA/PA66) scaffold material that was cultured with the rat bone marrow mesenchymal stem cells (rBMSCs), under the static culture condition and the dynamic perfusion culture conditionin vitro, and to investigate whether the 3D perfusion culture condition was better in provoking proliferation of rBMSCs than the 3D static culture condition. The Methyl thiazolyl tetrazolium (MTT) assay, alkaline phosphatase (ALP) activity assay, Osteocalcin (OCN) assay and scanning electron microscope (SEM) were used to observe the proliferation and differentiation of rBMSCs. The samples were respectively harvested at 1st, 3rd, 7th, 14th, and 21st days and effect comparisons were made between the two of the culture conditions. The results showed that values of MTT, ALP, and OCN were increased continuously and revealed a significant difference between the two culture conditions (p< 0.05). On the 14th day, SEM revealed calcified nodules 2–8 μm in diameter in the lamellar structure. Under the static culture condition, the pores were covered with the cells looking like a piece of blanket, but under the perfusion culture condition the cells were observed to have a 3D lamellar structure. In conclusion, the porous n‐HA/PA66 scaffold material can be used as a good candidate material for the bone scaffold construction in the tissue engineering because of its excellent 3D structure, which can greatly improve the proliferation and differentiation of rBMSCs and make them proliferate and osteogenesis even better under the perfusion culture condition. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.
Group Differential for Attainment and Failure Indicators
Authors: Nathan Hippu Salk Kristle , Mishra Srijit
Published: January 2013

The study revisits the properties of group differential (GD) measures and extends it to include monotonicity and policy sensitivity axioms. Imposing level sensitivity, which indicates that a given gap is worse off at higher (lower) level of attainment (failure), the study concurs that ‘simple difference’ and ‘simple ratio’ are the most basic GD measures for attainment and failure indicators, respectively. It proposes two new measures, one each for attainment and failure, which have certain advantages from a policy implication perspective. An empirical illustration has been provided by taking two indicators from Millennium Development Goals for different regions of the world. Copyright © 2013 John Wiley & Sons, Ltd.