bluuebunny/crossref_metadata_2025 huggingface dataset:
Dark rearing alters the normal development of spatiotemporal response properties but not of contrast detection threshold in mouse retinal ganglion cells
Authors: Akimov Nikolay P. , Rentería René C.
Published: January 2014

The mouse visual system is immature when the eyes open two weeks after birth. As in other mammals, some of the maturation that occurs in the subsequent weeks is known to depend on visual experience. Development of the retina, which as the first stage of vision provides the visual information to the brain, also depends on light‐driven activity for proper development but has been less well studied than visual cortical development. The critical properties for retinal encoding of images include detection of contrast and responsiveness to the broad range of temporal stimulus frequencies present in natural stimuli. Here we show that contrast detection threshold and temporal frequency response characteristics of ON and OFF retinal ganglion cells (RGCs), which are poor at eye opening, subsequently undergo maturation, improving RGC performance. Further, we find that depriving mice of visual experience from before birth by rearing them in the dark causes ON and OFF RGCs to have smaller receptive field centers but does not affect their contrast detection threshold development. The modest developmental increase in temporal frequency responsiveness of RGCs in mice reared on a normal light cycle was inhibited by dark rearing only in ON but not OFF RGCs. Thus, these RGC response characteristics are in many ways unaffected by the experience‐dependent changes to synaptic and spontaneous activity known to occur in the mouse retina in the two weeks after eye opening, but specific differences are apparent in the ON vs. OFF RGC populations. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 692–706, 2014
Modelling changes in grassland hydrological cycling along an elevational gradient in the Alps
Authors: Della Chiesa S. , Bertoldi G. , Niedrist G. , Obojes N. , Endrizzi S. , Albertson J. D. , Wohlfahrt G. , Hörtnagl L. , Tappeiner U.
Published: January 2014

The effects of elevation on surface water fluxes in dry alpine grassland ecosystems were investigated along an elevational transect between 1000 and 2000 m above sea level established in the Vinschgau/Venosta valley, a relatively dry region in the Italian Alps. The GEOtop‐dv hydrological model was employed in point‐scale mode to model the effects of the elevation gradient on snow water equivalent (SWE), soil water content (θ), evapotranspiration (ET), aboveground biomass (Bag) and water use efficiency (WUE) in different climatic conditions. Results show that SWE decreased strongly with decreasing elevation but was also affected by the interannual variability of meteorological drivers. During warmer years, the magnitude of changes in SWE was mitigated at higher altitudes while exacerbated below 1500 m. θ dynamics indicated that water stress conditions for vegetation currently occur at 1000 m each year, while only a warmer and drier year caused drought at 1500 m, and no water stress was found at 2000 m.

ET, Bag and WUE did not decrease with elevation but showed a maximum at an intermediate elevation around 1500 m because of the contrasting trends of a shorter vegetation season at higher elevations and water stress at lower elevations, where, in fact, irrigation is needed to maintain grassland productivity. A simulation based on long‐term climatic conditions in combination with a sensitivity analysis of precipitation change showed that this effect is more pronounced during drier years, while for the wettest years, ET tended to decrease with increasing elevation. Taking these findings together, this study suggests that in relatively dry climatic conditions, mountain areas generally act as ‘water towers’ above 1500 m. Quantifying this critical threshold and its likely future variation under climate change scenarios is a challenge for water resource research in the Alpine region and can help stakeholders in planning future mitigation strategies. Copyright © 2014 John Wiley & Sons, Ltd.
Tunable Epoxidation of Single‐Walled Carbon Nanotubes by Isolated Methyl(trifluoromethyl)dioxirane
Authors: Annese Cosimo , D'Accolti Lucia , Giambastiani Giuliano , Mangone Annarosa , Milella Antonella , Tuci Giulia , Fusco Caterina
Published: January 2014

Organic functionalization of carbon nanotube sidewalls is a tool of primary importance in material science and nanotechnology, equally from a fundamental and an applicative point of view. In this paper, a mild and easily tunable approach to the sidewall decoration of single‐walled carbon nanotubes (SWCNTs) with epoxides and their subsequent derivatization (ring opening) upon treatment with reactive nucleophiles is presented. The treatment of HiPco purified SWCNTs with dioxirane solutions results in highly oxidized CNTs, which are used as electrophilic platforms for their successive derivatization/functionalization. As a result of the choice of accessible, easy to handle and store dioxiranes, multiple oxidation cycles could be performed on the same sample, thus allowing for a final improvement in the extent of oxidation at the CNT sidewall.
Enhanced biodegradation of phenanthrene using different inoculum types in a microbial fuel cell
Authors: Adelaja Oluwaseun , Keshavarz Tajalli , Kyazze Godfrey
Published: January 2014

Environmental pollution by petroleum hydrocarbons from contaminated groundwater and soils is a serious threat to human health. Microbial fuel cells (MFCs) could be employed in the treatment of these recalcitrant pollutants with concomitant bioelectricity generation. In this study, the use of MFCs in biodegradation of phenanthrene, a model hydrocarbon, was investigated with respect to its biodegradation rate, biodegradation efficiency, and power production using a range of inocula (Shewanella oneidensis MR1 14063, Pseudomonas aeruginosa NCTC 10662, mixed cultures, and combinations thereof). All the inocula showed high potentials for phenanthrene degradation with a minimum degradation efficiency of 97%. The best overall performing inoculum was anaerobically digested sludge supplemented with P. aeruginosa NCTC 10662, having a degradation rate, maximum power density and chemical oxygen demand removal efficiency of 27.30 μM/d, 1.25 mW/m2 and 65.6%, respectively. Adsorption of phenanthrene on the carbon anode was also investigated; it conformed to a Type II adsorption isotherm and could be modelled using a modified Brunauer, Emmett and Teller model with a maximum monolayer capacity of 0.088 mg/cm2. This work highlights the possibility of using MFCs to achieve high degradation rates of phenanthrene through co‐metabolism and could potentially be used as a replacement of permeable reactive barriers for remediation of hydrocarbon‐contaminated groundwater.
Effect of TiO2, Al2O3, and Fe3O4 nanoparticles on phosphorus removal from aqueous solution
Authors: Moharami Somayeh , Jalali Mohsen
Published: January 2014

Phosphorus (P) removal from aqueous solutions was investigated using TiO2, Al2O3, and Fe3O4 nanoparticles (NPs). Adsorption study was performed to determine the optimum operation conditions such as adsorption time, temperature, pH, and adsorbent dosage. Sorption isotherms were well described by linear, Freundlich and Langmuir models. The maximum adsorption capacity of P was 28.3, 24.4, and 21.5 mg g−1 for TiO2, Fe3O4 and Al2O3, respectively. Desorption analysis showed that the desorption capacities were in an order of Al2O3 > Fe3O4 > TiO2. Kinetic data were best fitted with pseudo‐second‐order and intra‐particle diffusion kinetic models. Scanning electron microscopy (SEM), energy dispersive X‐ray (XRD), and NPs solution saturation indices (SI) before and after P sorption showed that the main mechanism of P sorption by TiO2 was adsorption, whereas P sorption by Al2O3 and Fe3O4 were due to adsorption and precipitation. Results showed that double layer model (DLM) could be modeled P adsorption onto adsorbents over a wide range of pH. Thermodynamic parameters confirmed the endothermic and not spontaneity nature of the P adsorption. These NPs have potential for use as efficient sorbents for the removal of P from aqueous solutions and TiO2 NPs were identified as the most promising sorbent due to their high metal uptake. © 2014 American Institute of Chemical Engineers Environ Prog, 33: 1209–1219, 2014
A two‐level cooperative game‐based approach for joint relay selection and distributed resource allocation in MIMO‐OFDM‐based cooperative cognitive radio networks
Authors: Adian Mehdi Ghamari , Aghaeinia Hassan
Published: January 2014

We consider the downlink of a multi‐input multi‐output orthogonal frequency‐division multiplexing‐based cooperative cognitive radio network in which the secondary users (SUs) with extra resources work as relay to help the SUs with less available resources to improve their utility in terms of the throughput and fairness by forming a coalition graph. We model the problem of joint relay selection and power allocation in multi‐input multi‐output orthogonal frequency‐division multiplexing‐based cooperative cognitive radio network as a two‐level cooperative game problem, and the objectives of this work are twofold. Firstly, we assign each weak SU to one of the relays (rich SUs) through solving a problem achieved by a non‐transferable utility coalition graph game, and this comprises the first level of the game. Secondly, we jointly allocate available channels to the SUs such that no subchannel is allocated to more than one SU and simultaneously optimise the transmit covariance matrices of nodes based on the Nash bargaining solution, which is the second level of the game. We further model the network as a multi‐cell scenario with small serving areas. After relaxing the problem and convexifying the relaxed version, we develop an optimal distributed algorithm, using dual decomposition. Afterwards, we propose a dynamic distributed resource allocation algorithm for this purpose. Simulations confirm the convergence of our distributed algorithms to the globally optimal solution of the two‐level game. Copyright © 2014 John Wiley & Sons, Ltd.
GATA4 loss in the septum transversum mesenchyme promotes liver fibrosis in mice
Authors: Delgado Irene , Carrasco Manuel , Cano Elena , Carmona Rita , García-Carbonero Rocío , Marín-Gómez Luis M. , Soria Bernat , Martín Francisco , Cano David A. , Muñoz-Chápuli Ramón , Rojas Anabel
Published: January 2014

The zinc finger transcription factor GATA4 controls specification and differentiation of multiple cell types during embryonic development. In mouse embryonic liver, Gata4 is expressed in the endodermal hepatic bud and in the adjacent mesenchyme of the septum transversum. Previous studies have shown that Gata4 inactivation impairs liver formation. However, whether these defects are caused by loss of Gata4 in the hepatic endoderm or in the septum transversum mesenchyme remains to be determined. In this study, we have investigated the role of mesenchymal GATA4 activity in liver formation. We have conditionally inactivated Gata4 in the septum transversum mesenchyme and its derivatives by using Cre/loxP technology. We have generated a mouse transgenic Cre line, in which expression of Cre recombinase is controlled by a previously identified distal Gata4 enhancer. Conditional inactivation of Gata4 in hepatic mesenchymal cells led to embryonic lethality around mouse embryonic stage 13.5, likely as a consequence of fetal anemia. Gata4 knockout fetal livers exhibited reduced size, advanced fibrosis, accumulation of extracellular matrix components and hepatic stellate cell (HSC) activation. Haploinsufficiency of Gata4 accelerated CCl4-induced liver fibrosis in adult mice. Moreover, Gata4 expression was dramatically reduced in advanced hepatic fibrosis and cirrhosis in humans. Conclusions: Our data demonstrate that mesenchymal GATA4 activity regulates HSC activation and inhibits the liver fibrogenic process. (Hepatology 2014;59:2358–2370)
Alterations in classical and nonclassical HLA expression in recurrent and progressive HPV‐induced usual vulvar intraepithelial neoplasia and implications for immunotherapy
Authors: van Esch E.M.G. , Tummers B. , Baartmans V. , Osse E.M. , ter Haar N. , Trietsch M.D. , Hellebrekers B.W.J. , Holleboom C.A.G. , Nagel H.T.C. , Tan L.T. , Fleuren G.J. , van Poelgeest M.I.E. , van der Burg S.H. , Jordanova E.S.
Published: January 2014

Immunotherapy of usual vulvar intraepithelial neoplasia (uVIN) is promising; however, many patients still fail to show clinical responses, which could be explained by an immune escape through alterations in human leukocyte antigen (HLA) expression. Therefore, we analyzed a cohort of patients with a primary (n = 43) and subsequent recurrent uVIN lesion (n = 20), vaccine‐treated uVIN patients (n = 12), patients with human papillomavirus (HPV)‐induced vulvar carcinoma (n = 21) and healthy controls (n = 26) for the expression of classical HLA‐class I/II and nonclassical HLA‐E/‐G and MHC class I chain‐related molecule A (MICA). HLA‐class I was downregulated in 70% of uVIN patients, including patients with a clinical response to immunotherapy. Downregulation of HLA‐class I is probably reversible, as only 15% of the uVIN cases displayed loss of heterozygosity (LOH) and HLA‐class I could be upregulated in uVIN keratinocyte cultures by interferon γ. HLA‐class I downregulation is more frequently associated with LOH in vulvar carcinomas (25–55.5%). HLA‐class II was found to be focally expressed in 65% of uVIN patients. Of the nonclassical molecules, MICA was downregulated in 80% of uVIN whereas HLA‐E and ‐G were expressed in a minority of cases. Their expression was more prominent in vulvar carcinoma. No differences were found between the alterations observed in paired primary and recurrent uVIN. Importantly, downregulation of HLA‐B/C in primary uVIN lesions was associated with the development of recurrences and progression to cancer. We conclude that downregulation of HLA is frequently observed in premalignant HPV‐induced lesions, including clinical responders to immunotherapy, and is associated with worse clinical outcome. However, in the majority of cases downregulation may still be reversible.
PDLLA/PRGD/β‐TCP conduits build the neurotrophin‐rich microenvironment suppressing the oxidative stress and promoting the sciatic nerve regeneration
Authors: Qiu Tong , Yin Yixia , Li Binbin , Xie Lijuan , Yan Qiongjiao , Dai Honglian , Wang Xinyu , Li Shipu
Published: January 2014

A novel nerve guidance conduit comprising poly{(lactic acid)‐co‐[(glycolic acid)‐alt‐(l‐lysine)]} (PRGD), poly (d,l‐lactic acid) (PDLLA) and β‐tricalcium phosphate (β‐TCP) was constructed to facilitate the peripheral nerve regeneration. From the comparative study, PDLLA/PRGD/β‐TCP conduit achieved the best recovery in regard of the ultrastructure observation and the SFI evaluation. At the first stage of the injury (7 days), the maximum expression augments in ZnSOD (6.4 folds) and GPX4 (6.8 folds) were observed in PDLLA/PRGD/β‐TCP group; while striking rise in actin (6.8 folds), tubulin (5.6 folds), and ERM components expressions were observed later (35 days). Meanwhile, compared with PDLLA and PDLLA/PRGD conduits, PDLLA/PRGD/β‐TCP conduits achieved the highest local nerve growth factor (NGF) content and an accumulating BDNF content. We speculated that addition of RGD and β‐TCP in the composites were the main positive factors to build the microenvironment rich in NGF and BDNF, which help to counteract with the oxidative stress and to boost the cytoskeletal protein expressions. Therefore, PDLLA/PRGD/β‐TCP could be promising composites used in peripheral nerve regeneration. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3734–3743, 2014.
Osteoactivin Promotes Osteoblast Adhesion Through HSPG and αvβ1 Integrin
Authors: Moussa Fouad M. , Hisijara Israel Arango , Sondag Gregory R. , Scott Ethan M. , Frara Nagat , Abdelmagid Samir M. , Safadi Fayez F.
Published: January 2014

Osteoactivin (OA), also known as glycoprotein nmb (gpnmb) plays an important role in the regulation of osteoblast differentiation and function. OA induced osteoblast differentiation and function in vitro by stimulating alkaline phosphatase (ALP) activity, osteocalcin production, nodule formation, and matrix mineralization. Recent studies reported a role for OA in cell adhesion and integrin binding. In this study, we demonstrate that recombinant osteoactivin (rOA) as a matricellular protein stimulated adhesion, spreading and differentiation of MC3T3‐E1 osteoblast‐like cells through binding to αvβ1 integrin and heparan sulfated proteoglycans (HSPGs). MC3T3‐E1 cell adhesion to rOA was blocked by neutralizing anti‐OA or anti‐αv and β1 integrin antibodies. rOA stimulated‐osteoblast adhesion was also inhibited by soluble heparin and sodium chlorate. Interestingly, rOA stimulated‐osteoblast adhesion promoted an increase in FAK and ERK activation, resulting in the formation of focal adhesions, cell spreading and enhanced actin cytoskeleton organization. In addition, differentiation of primary osteoblasts was augmented on rOA coated‐wells marked by increased alkaline phosphatase staining and activity. Taken together, these data implicate OA as a matricellular protein that stimulates osteoblast adhesion through binding to αvβ1 integrin and cell surface HSPGs, resulting in increased cell spreading, actin reorganization, and osteoblast differentiation with emphasis on the positive role of OA in osteogenesis. J. Cell. Biochem. 115: 1243–1253, 2014. © 2014 Wiley Periodicals, Inc.
Protective Action of Liraglutide in Beta Cells Under Lipotoxic Stress Via PI3K/Akt/FoxO1 Pathway
Authors: Shao Shiying , Nie Mingbo , Chen Cai , Chen Xi , Zhang Muxun , Yuan Gang , Yu Xuefeng , Yang Yan
Published: January 2014

Liraglutide, a modified form of glucagon‐like peptide‐1 (GLP‐1), has been found to improve beta cell function in type 2 diabetes (T2DM). However, the effect of liraglutide on beta cell function under lipotoxic stress and the underlying molecular mechanisms remain unclear. In the present study, we investigated the role of PI3K/Akt/FoxO1 signaling in liraglutide‑involved beta cell protection in high free fatty acids (FFAs) condition. The apoptosis, proliferation, and insulin secretion capability of MIN6 cells and islets from C57BL/6J mice were evaluated when exposed to FFAs with/without liraglutide. The expression of effectors involved in PI3K/Akt/FoxO1signalling pathway was detected by real‐time PCR and western blotting in MIN6 cells and islets from C57BL/6J mice. Liraglutide substantially inhibited the lipoapoptosis and improved the proliferation and insulin secretion of beta cells in high FFAs condition. Western blot revealed that the phosphorylation of Akt and FoxO1 was markedly decreased under lipid stress but was elevated when treated with liraglutide. Moreover, FFAs could up‐regulate the expression levels of p27, Bax, Cidea but down‐regulate the expression levels of Pdx‐1, MafA, and NeuroD in beta cells, which was canceled by the addition of liraglutide. Moreover, LY294002, a PI3K inhibitor, could significantly abrogate all the protective actions of liraglutide against lipotoxicity. We concluded that liraglutide markedly improved beta cell function under lipid stress and that the protective action of liraglutide was mediated by activation of PI3K/Akt, which resulted in inactivation of FoxO1 along with the down‐regulation of p27, Bax, Cidea and up‐regulation of Pdx‐1, MafA, and NeuroD expressions. J. Cell. Biochem. 115: 1166–1175, 2014. © 2013 Wiley Periodicals, Inc.
Structural analysis of protein‐ligand interactions: the binding of endogenous compounds and of synthetic drugs
Authors: Gallina Anna M. , Bork Peer , Bordo Domenico
Published: January 2014

The large number of macromolecular structures deposited with the Protein Data Bank (PDB) describing complexes between proteins and either physiological compounds or synthetic drugs made it possible a systematic analysis of the interactions occurring between proteins and their ligands. In this work, the binding pockets of about 4000 PDB protein‐ligand complexes were investigated and amino acid and interaction types were analyzed. The residues observed with lowest frequency in protein sequences, Trp, His, Met, Tyr, and Phe, turned out to be the most abundant in binding pockets. Significant differences between drug‐like and physiological compounds were found. On average, physiological compounds establish with respect to drugs about twice as many hydrogen bonds with protein atoms, whereas drugs rely more on hydrophobic interactions to establish target selectivity. The large number of PDB structures describing homologous proteins in complex with the same ligand made it possible to analyze the conservation of binding pocket residues among homologous protein structures bound to the same ligand, showing that Gly, Glu, Arg, Asp, His, and Thr are more conserved than other amino acids. Also in the cases in which the same ligand is bound to unrelated proteins, the binding pockets showed significant conservation in the residue types. In this case, the probability of co‐occurrence of the same amino acid type in the binding pockets could be up to thirteen times higher than that expected on a random basis. The trends identified in this study may provide an useful guideline in the process of drug design and lead optimization. Copyright © 2014 John Wiley & Sons, Ltd.
Reconciliation of classical and reacted‐site probability approaches to allowance for ligand multivalence in binding studies
Authors: Lollar Pete , Winzor Donald J.
Published: January 2014

The objective of this investigation is to engender greater confidence in the validity of binding equations derived for multivalent ligands on the basis of reacted‐site probability theory. To that end, a demonstration of the theoretical interconnection between expressions derived by the classical stepwise equilibria and reacted‐site probability approaches for univalent ligands is followed by the use of the traditional stepwise procedure to derive binding equations for bivalent and trivalent ligands. As well as demonstrating the unwieldy nature of the classical binding equation for multivalent ligand systems, that exercise has allowed numerical simulation to be used to illustrate the equivalence of binding curves generated by the two approaches. The advantages of employing a redefined binding function for multivalent ligands are also confirmed by subjecting the simulated results to a published analytical procedure that has long been overlooked. Copyright © 2013 John Wiley & Sons, Ltd.
Enthalpic factors override the polyelectrolyte effect in the binding of EGR1 transcription factor to DNA
Authors: Mikles David C. , Bhat Vikas , Schuchardt Brett J. , McDonald Caleb B. , Farooq Amjad
Published: January 2014

Protein–DNA interactions are highly dependent upon salt such that the binding affinity precipitously decreases with increasing salt concentration in a phenomenon termed as the polyelectrolyte effect. In this study, we provide evidence that the binding of early growth response (EGR) 1 transcription factor to DNA displays virtually zero dependence on ionic strength under physiological salt concentrations and that such feat is accomplished via favorable enthalpic contributions. Importantly, we unearth the molecular origin of such favorable enthalpy and attribute it to the ability of H382 residue to stabilize the EGR1–DNA interaction via both intermolecular hydrogen bonding and van der Waals contacts against the backdrop of salt. Consistent with this notion, the substitution of H382 residue with other amino acids faithfully restores salt‐dependent binding of EGR1 to DNA in a canonical fashion. Remarkably, H382 is highly conserved across other members of the EGR family, implying that changes in bulk salt concentration are unlikely to play a significant role in modulating protein–DNA interactions central to this family of transcription factors. Taken together, our study reports the first example of a eukaryotic protein–DNA interaction capable of overriding the polyelectrolyte effect. Copyright © 2014 John Wiley & Sons, Ltd.
Generation and epitope mapping of a sub‐group cross‐reactive anti‐respiratory syncytial virus G glycoprotein monoclonal antibody which is protective in vivo
Authors: Robinson Mark J. , Tan Cheng‐Siang , Fenwick Fiona , Chambers Chris J. , Routledge Edward G. , Toms Geoffrey L.
Published: January 2014

Passively administered antibodies to conserved epitopes on the attachment (G) glycoprotein of human respiratory syncytial virus (hRSV) have potential in the immunoprophylaxis of human infections. This study set out to generate monoclonal antibodies (MAbs) recognizing all prevalent lineages of HRSV and capable of immunoprophylaxis in mice. Two murine MAbs of broad specificity for prevalent virus strains were generated by immunization of mice with hRSV of sub‐group A followed by selection of hybridomas on recombinant G glycoprotein from a sub‐group B virus. The anti‐G hybridomas generated secreted antibody of high affinity but negligible neutralizing capacity one of which was tested in mice and found to be protective against live virus challenge. Western blotting and partial epitope mapping on transiently expressed G‐glycoprotein fragments indicate that these antibodies recognize a complex epitope on the protein backbone of the molecule involving residues both C′‐ and N‐terminal to the central conserved motif. J. Med. Virol. 86:1267–1277, 2014. © 2014 Wiley Periodicals, Inc.
Simultaneous determination of major type‐B trichothecenes and the de‐epoxy metabolite of deoxynivalenol in chicken tissues by HPLC–MS/MS
Authors: Xu Lixiao , Zhang Guijun , Guo Chunna , Zhang Yaping , Zhang Yi , Zheng Jianlong , Yang Haicui , Yang Dexue , He Limin , Zeng Zhenling , Fang Binghu
Published: January 2014

In this study, a specific and sensitive LC–MS/MS method for the simultaneous analysis of type‐B trichothecenes (deoxynivalenol, 3‐acetyldeoxynivalenol, and 15‐acetyldeoxynivalenol) and the de‐epoxy metabolite of deoxynivalenol (de‐epoxy‐deoxynivalenol) in chicken muscle, liver, kidney, and fat tissues was developed and validated. The method involved an extraction step using ethyl acetate, followed by the evaporation of the supernatant, which was further purified by an Oasis HLB SPE cartridge (Waters, Milford, MA, USA). Chromatographic separation was performed on a C18 column by detection with MS in multiple‐reaction monitoring mode and using a gradient elution program with 0.1% formic acid in water and methanol. The correlation coefficients (r) for each calibration curve were >0.99 within the experimental concentration range. The extraction recoveries ranged from 73.7 to 106.4%, with intraday and interday RSD < 11.6% at three levels of concentrations of 2, 10, and 100 μg/kg. The decision limits and the detection capabilities of the analytes in the chicken tissues ranged from 0.16 to 0.92 and 0.68 to 2.07 μg/kg, respectively. The results demonstrated the applicability of this sensitive procedure to the determination of trichothecenes in chicken tissue samples.
Written informed consent for living liver donor evaluation: Compliance with centers for medicare and medicaid services and organ procurement and transplantation network guidelines and alibi offers
Authors: Thiessen Carrie , Kim Yunsoo A. , Yoo Peter S. , Rodriguez-Davalos Manuel , Mulligan David , Kulkarni Sanjay
Published: January 2014

We examined written informed consent forms for living liver donor evaluations to determine whether they incorporated elements required by the Centers for Medicare and Medicaid Services (CMS) and suggested by the Organ Procurement and Transplantation Network (OPTN). We contacted each of the 41 US centers that performed at least 1 living donor liver transplant in 2011; 37 centers reported active living donor evaluation programs. Twenty-six centers shared their consent form for living donor evaluation (response rate = 70%). Each document was double-coded for consent element content. We found that 57% of the centers included the 9 mandated CMS elements. Although the OPTN guidelines are non-binding, 78% of the centers used consent forms that addressed at least two-thirds of the elements recommended by OPTN. Only 17% of the centers provided written offers of an alibi to donors who withdrew from the evaluation. On the basis of our findings, we offer suggestions that may be relevant to ongoing revisions to the OPTN living liver donor consent policy and may help centers to improve the clarity of their written consent forms. Liver Transpl 20:416–424, 2014. © 2014 AASLD.
Cell surfactomes of two endometrial epithelial cell lines that differ in their adhesiveness to embryonic cells
Authors: Bhagwat Sonali R. , Redij Tejashree , Phalnikar Kruttika , Nayak Sumeet , Iyer Swati , Gadkar Sushama , Chaudhari Uddhav , Kholkute Sanjeeva D. , Sachdeva Geetanjali
Published: January 2014

Adhesiveness of the endometrial epithelium to an embryo plays a critical role in the initiation of pregnancy. Loss or gain of adhesiveness also dictates the potential of endometrial epithelial cells to metastasize, an event that can result from certain genetic insults. A proteomics‐based exploration of the “adhesiveness” these epithelial cells was employed that could identify targets that could disrupt embryo–endometrium interactions and/or metastasis of endometrial cancer cells. The present study defined the surfactomes of two human endometrial epithelial cell lines known for their differential adhesiveness to embryonic cells. Comparative, two‐dimensional electrophoretic analysis of the surfactomes of RL95‐2 (exhibiting higher adhesiveness to the embryonic cell line JAr) and HEC‐1A (exhibiting reduced adhesiveness to JAr cells) revealed 55 differentially enriched proteins. Of these, 10 proteins were identified by MALDI‐TOF/TOF or LC–MS/MS. TUBB2C, ADAMTS3, and elongation factor beta were more abundant on the HEC‐1A cell surface whereas HSP27, HSPA9, GP96, CRT, Tapasin‐ERP57, PDI, and β‐actin were more abundant on the RL95‐2 cell surface. Nano LC–MS/MS was also employed to generate a more comprehensive surfactomes of RL95‐2 and HEC‐1A. The study also demonstrated a pro‐adhesive role of CRT and HSPA9 and an anti‐adhesive role of TUBB2C populations found on the cell surface. In brief, this study identifies the cell‐surface protein complements of two human endometrial epithelial cell lines, and reveals the role of three proteins in heterotypic cell adhesion. Mol. Reprod. Dev. 81: 326–340, 2014. © 2014 Wiley Periodicals, Inc.
Comparison of peripheral sudomotor sensitivity to acetylcholine in endurance and non‐endurance trained male subjects
Authors: Shin Young Oh , Lee Jeong Beom
Published: January 2014

Introduction: We investigated the effect of endurance and non‐endurance training on peripheral sudomotor sensitivity. Methods: The quantitative sudomotor axon reflex test (QSART) was performed. Results: Endurance‐trained subjects (ET, long‐distance runners) had a significantly shorter onset time of sweating, greater sweat volume, increased density of activated sweat glands and sweat gland output per single activated gland, greater volume of transepidermal water loss, and higher skin temperature compared with those in the other 2 groups [non–endurance‐trained group (NET), sedentary control group (CT)]. NET subjects (baseball players) had a tendency to increase in these variables; thus, some values were greater than control subjects. Conclusions: These results suggest that endurance training much more effectively modifies sudomotor sensitivity than non‐endurance training. Muscle Nerve 50: 407–412, 2014
Knee extensor fatigue resistance of young and older men and women performing sustained and brief intermittent isometric contractions
Authors: Mcphee Jamie S. , Maden‐Wilkinson Thomas M. , Narici Marco V. , Jones David A. , Degens Hans
Published: January 2014

Introduction: Susceptibility to muscle fatigue during aging could depend on muscle activation patterns. Methods: Young (mean age, 22 years) and older (mean age 70 years) men and women completed two fatigue tests of knee extensor muscles using voluntary and electrically stimulated contractions. Results: Older subjects displayed a shift to the left of the torque‐frequency relationship and held a sustained voluntary isometric contraction at 50% maximal strength for significantly longer than young (P < 0.001). Young and old showed similar fatigue during electrically induced, intermittent isometric contractions (1‐s on, 1‐s off for 2 min), but women fatigued less than men (P = 0.001). Stronger muscles fatigued more quickly, and slower contractile properties were associated with longer sustained contractions. Conclusions: The slowing and weakness of older muscle was associated with superior fatigue resistance during sustained isometric contractions. Young and old showed similar fatigue following a series of brief, intermittent contractions, but women fatigued less than men. Muscle Nerve 50: 393–400, 2014
Endohedral fullerenes: the importance of electronic, size and shape complementarity between the carbon cages and the corresponding encapsulated clusters
Authors: Cerón Maira R. , Li Fang‐Fang , Echegoyen Luis A.
Published: January 2014

Cage‐cluster complementarity is of crucial importance in determining the sizes and structures, as well as the properties of endohedral fullerenes. The encapsulated atoms or clusters, which are typically in a positively charged state, are irreversibly, mechanically, and electrostatically trapped inside the typically negatively charged cages. These rather exotic compounds exhibit exquisitely complementary properties between their components. Here, we present a short overview to show that size and shape are crucial in determining the specific structures that are formed, and the presence of electrostatic interactions result in structural motifs that are never observed for pristine fullerene cages. Copyright © 2014 John Wiley & Sons, Ltd.
Evaluation of matrix metalloproteinase‐2 in lung cancer
Authors: Ali‐Labib Randa , Louka Manal Louis , Galal Iman Hassan El‐Sayed , Tarek Marwa
Published: January 2014

Purpose

There is an obvious need to diagnose lung cancer using novel noninvasive and sensitive biomarkers. In this regard, the aim of the present study was to evaluate and compare sputum matrix metalloproteinase 2 (MMP‐2) in relation to serum MMP‐2 of lung cancer patients and other nonmalignant lung diseases in order to establish a new diagnostic and prognostic biomarker with a valid noninvasive technique.

Experimental design

Group 1 included 32 newly diagnosed lung cancer patients and group 2 included 20 patients with benign pulmonary diseases. In addition, 38 healthy subjects served as control group. MMP‐2 activity levels were evaluated in serum and sputum samples of the studied groups using ELISA and zymography techniques.

Results

There was a highly significant increase in serum and sputum MMP‐2 levels in malignant group in comparison with benign and control groups. In addition, there was a significant difference in the levels of serum and sputum MMP‐2 as regards the different histopathological types of lung cancer and advanced stages of lung cancer. Gelatin zymography was used to confirm the enzymatic activity of MMP‐2. A higher MMP‐2 activity was detected in lung cancer group in comparison with benign and control groups.

Conclusions and clinical relevance

Serum and to a larger extent sputum MMP‐2 appear to be potential noninvasive markers for detecting lung cancer.
A decade of proteomics studies of glaucomatous neurodegeneration
Authors: Tezel Gülgün
Published: January 2014

Glaucoma is a leading cause of blindness; however, limited understanding of the molecular mechanisms involved in optic nerve degeneration hinders the development of improved treatment strategies. Proteomics techniques that combine the protein chemistry, MS, and bioinformatics offer the opportunity to shed light on molecular mechanisms so that new treatment strategies can be developed for immunomodulation, neuroprotection, neurorescue, neuroregeneration, and function gain in glaucoma. The proteomics technologies also hold great promise for biomarker discovery, another important goal of glaucoma research. As much as developing new treatment strategies, molecular biomarkers are strongly needed for early diagnosis of glaucoma, prediction of its prognosis, and monitoring the responses to new treatments. It is now a decade that the proteomics analysis techniques have been using to move glaucoma research forward. This review will focus on valuable applications of proteomics in the field of glaucoma research and highlight the power of this analytical toolbox in translational and clinical research toward better characterization and improved treatment of glaucomatous neurodegeneration and discovery of glaucoma‐related molecular biomarkers.
Pentraxins and IgA share a binding hot‐spot on FcαRI
Authors: Lu Jinghua , Marjon Kristopher D. , Mold Carolyn , Marnell Lorraine , Du Clos Terry W. , Sun Peter
Published: January 2014

The pentraxins, C‐reactive protein (CRP), and serum amyloid P component (SAP) have previously been shown to function as innate opsonins through interactions with Fcγ receptors. The molecular details of these interactions were elucidated by the crystal structure of SAP in complex with FcγRIIA. More recently, pentraxins were shown to bind and activate FcαRI (CD89), the receptor for IgA. Here, we used mutations of the receptor based on a docking model to further examine pentraxin recognition by FcαRI. The solution binding of pentraxins to six FcαRI alanine cluster mutants revealed that mutations Y35A and R82A, on the C‐and F‐strands of the D1 domain, respectively, markedly reduced receptor binding to CRP and SAP. These residues are in the IgA‐binding site of the receptor, and thus, significantly affected receptor binding to IgA. The shared pentraxin and IgA‐binding site on FcαRI is further supported by the results of a solution binding competition assay. In addition to the IgA‐binding site, pentraxins appear to interact with a broader region of the receptor as the mutation in the C′‐strand (R48A/E49A) enhanced pentraxin binding. Unlike Fcγ receptors, the H129A/I130A and R178A mutations on the BC‐ and FG‐loops of D2 domain, respectively, had little effect on FcαRI binding to the pentraxins. In conclusion, our data suggest that the pentraxins recognize a similar site on FcαRI as IgA.
The Distinction Between Experimental and Historical Sciences as a Framework for Improving Classroom Inquiry
Authors: GRAY RON
Published: January 2014

Inquiry experiences in secondary science classrooms are heavily weighted toward experimentation. We know, however, that many fields of science (e.g., evolutionary biology, cosmology, and paleontology), while they may utilize experiments, are not justified by experimental methodologies. With the focus on experimentation in schools, these fields of science are often not included in the inquiry experiences our students receive. I propose utilizing the distinction between experimental and historical sciences as a way to improve the diversity of scientific methodologies represented in the science classroom. This distinction can provide a framework for teachers to examine their own inquiry practices in light of the diverse methodologies present in science today. In this paper, the framework is presented and analyzed in light of the scientific practices highlighted in the Next Generation Science Standards and key concepts needed to discuss historical science methodologies are discussed.
Security risk assessment framework for cloud computing environments
Authors: Albakri Sameer Hasan , Shanmugam Bharanidharan , Samy Ganthan Narayana , Idris Norbik Bashah , Ahmed Azuan
Published: January 2014

Cloud computing has become today's most common technology buzzword. Despite the promises of cloud computing to decrease computing implementation costs and deliver computing as a service, which allows clients to pay only for what they need and use, cloud computing also raises many security concerns. Most popular risk assessment standards, such as ISO27005, NIST SP800‐30, and AS/NZS 4360, assume that an organization's assets are fully managed by the organization itself and that all security management processes are imposed by the organization. These assumptions, however, do not apply to cloud computing environments. Hence, this paper proposes a security risk assessment framework that can enable cloud service providers to assess security risks in the cloud computing environment and allow cloud clients to contribute in risk assessment. The proposed framework provides a more realistic and accurate risk assessment outcome by considering the cloud clients' evaluation of security risk factors and avoiding the complexity that can result from the involvement of clients in whole risk assessment process. Copyright © 2014 John Wiley & Sons, Ltd.
Anomaly detection and response approach based on mapping requests
Authors: Wan Ming , Zhang Hong‐Ke , Wu Tin‐Yu , Lo Chi‐Hsiang
Published: January 2014

There is an increasing consensus that the locator/identifier separation of IP address is necessary to resolve the scalability issues of current Internet routing architecture. After identifiers are separated from locators, an identifier‐to‐locator mapping service must be employed to map identifiers onto locators. From this point, this paper proposes an anomaly detection and response approach based on mapping requests. By using the cumulative sum algorithm for change point detection, this approach introduces the anomalous traffic detection of mapping requests to diagnose the aberrant network behaviors. Once alarming, two effective response methods can be chosen to control the anomalous attack traffic in real time. Furthermore, in order to decouple the mapping request traffic from the mapping cache, this approach not only takes into account the mapping cache timeout but also puts forward a practical mapping request threshold algorithm. In particular, our simulation results show that, compared with the anomaly detection approach based on network traffic, the proposed approach is more advantageous and efficient. In addition, we also discuss the possible false positive and false negative problems, which may be caused by some accidental phenomena. Copyright © 2014 John Wiley & Sons, Ltd.
Adding variables variation to Rainbow‐like scheme to enhance its security level against MinRank attack
Authors: Tan Yang , Tang Shaohua , Wang Ting
Published: January 2014

Rainbow is a very effective multivariate digital signature scheme proposed by J. Ding and D. Schmidt. In this paper, we define any scheme that has basic multilayer Rainbow structure as Rainbow‐like scheme. Then, we propose a way to enhance Rainbow‐like schemes’ security level against MinRank attack. In our construction, we simply turn some of their first layers’ Oil variables into Vinegar variables by adding corresponding quadratic terms. Copyright © 2014 John Wiley & Sons, Ltd.
Generating signatures with optimal overhead: practical paddings for signature schemes
Authors: Qian Haifeng , Zhou Yuan , Li Zhibin , Chen Zhijie
Published: January 2014

Optimal signatures (generating signatures as short as possible), which achieve the optimal bandwidth for communication, are extremely useful in bandwidth‐critical networks. Previous approaches use the random permutations with large block size as building blocks, which incurs less efficient implementations in the real world. Meanwhile, all the practical signature schemes are not optimal in bandwidth including PSS‐R (probabilistic signature scheme with message recovery ), FDH ( Full Domain Hash), and DSA (Digital Signature Algorithm). This paper presents three constructions for optimal signature schemes. All the proposals use both the random oracles and the ideal ciphers with smaller block sizes as building blocks to obtain optimal paddings for signature schemes. The ideal ciphers in our schemes can be implemented by real block ciphers (e.g., AES (Advanced Encryption Standard)‐256). Concrete implementations of these signature schemes can utilize the trapdoor permutations of Rabin and RSA, respectively. Surprisingly, RSA and Rabin (trapdoor permutations) lead to not only optimality in bandwidth but also a tight security. Therefore, besides yielding secure signatures with high efficiency, our proposals can also be flexibly applied to the bandwidth‐limited networks that reduces the communication cost as less as possible. Copyright © 2014 John Wiley & Sons, Ltd.
What nanomedicine in the clinic right now really forms nanoparticles?
Authors: Svenson Sonke
Published: January 2014

Some researchers believe nanomedicine will revolutionize healthcare and medicine through transformative new therapeutic tools. Nanocarriers, utilized to transport actives to the target site, are constructed from a wide range of materials. Nanocarriers can be grouped into self‐assembling (liposomes, micelles), processed (nanoparticles, emulsions), and chemically bound (dendrimers, silica‐based carriers, carbon nanotubes) structures. A review of nanomedicines on the market and in clinical translation reveals that the vast majority is based on liposomes, polymeric micelles, and nanoparticles. The increasing presence of these novel nanomedicines raises the question what nanomedicines in the clinic right now really form nanoparticles, i.e., are improvements we see from nanomedicines structure‐related or do they result from improved formulations? Do we even have sufficient data to address this question? The formation of nanocarriers is usually confirmed in vitro but little if any in vivo (let alone clinical) information is available. Given the large number of nanomedicines on the market and under clinical evaluation one clearly cannot expect to find a ‘one size fits all’ answer. Therefore, two case studies are discussed: the paclitaxel formulation Taxol® and its nanomedicine companions LEP‐ETU (liposome), Genexol®‐PM and NK105 (micelles), and Abraxane® (nanoparticle). Published pharmacokinetic data is utilized to find differences indicating nanocarrier delivery. The second case study involves structurally related camptothecin‐polymer conjugates CRLX101 (nanoparticles) and XMT‐1001 (prodrug). Structural differences are evaluated to discuss the different aggregation behavior. This opinion can only serve as first attempt to find a more general answer; clearly more data is needed from future studies.

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Emerging Technologies

Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease