bluuebunny/crossref_metadata_2025 huggingface dataset:
Variable Borohydride Hapticity in Nickel(II) Scorpionate Complexes [(TpR,Me)Ni(ηn‐BH4)]: TpR,Me = hydrotris{3‐R‐5‐methyl‐1‐pyrazolyl}borate; R = Ph, n = 3 vs. R = Me, n = 4
Authors: Kruse Colin P. , Deb Tapash , Aboelenen Ahmed M. , Anderson Caitlin M. , Petersen Jeffrey L. , Jensen Michael P.
Published: February 2016

A “second‐generation” scorpionate ligand was utilized to prepare the nickel(II) borohydride complex [(TpPh,Me)Ni(η3‐BH4)], wherein the borohydride was coordinated through two bridging B–H bonds, leaving two terminal B–H bonds uncoordinated as determined by X‐ray crystallography. The distorted square‐pyramidal complex is paramagnetic (S = 1), with 18 valence electrons, and contrasts with a previously reported 20‐electron pseudo‐octahedral “first‐generation” analogue, [(TpMe,Me)Ni(η4‐BH4)] (P. J. Desrochers, et al. Inorg. Chem. 2003, 42, 7945–7950). These distinct borohydride coordination modes were distinguished by FTIR spectroscopy, and rationalized by DFT calculations on simplified models, [(Tp)Ni(ηn‐BH4)] (n = 3, 4). The difference in borohydride hapticities is attributed to the steric effect of the scorpionate 3‐pyrazole phenyl substituents disposed proximally to the metal, thus demonstrating the subtle versatility of Trofimenko's scorpionate ligands in controlling ligand field geometries. The precursor complex [(TpPh,Me)Ni(κ2‐NO3)] was also prepared and characterized.
Bismuth Iodide Hybrid Organic‐Inorganic Crystal Structures and Utilization in Formation of Textured BiI3 Film
Authors: Nørby Peter , Jørgensen Mads Ry Vogel , Johnsen Simon , Brummerstedt Iversen Bo
Published: February 2016

Two new and one redetermination of metastable bismuth iodide hybrid organic‐inorganic structure incorporating the solvents 2,3,4,5‐tetrahydrothiophene 1,1‐dioxide Bi2I6·(C4H8O2S)2 (1), N,N‐dimethylmethanamide Bi3I12·Bi(C3H7NO)8 (2), and dimethyl sulfoxide Bi2I9·Bi(C2H6OS)8 (3), are reported. In these compounds the size and shape of the inorganic moiety can be selectively adjusted by choice of solvent, which takes the form of infinite neutral linear BiI3 chains in 1 and isolated Bi–I clusters [Bi3I12]3– in 2. The crystals are short‐lived and decompose to form BiI3 under ambient conditions. Highly textured BiI3 films can be fabricated by spin coating, which is shown for the case of 3.
Castor oil‐based waterborne polyurethanes with tunable properties and excellent biocompatibility
Authors: Liu Kai , Miao Shida , Su Zhiguo , Sun Lijing , Ma Guanghui , Zhang Songping
Published: February 2016

Biopolymers materials with tunable properties are the spotlight in the polymer molecules design and synthesis. Here, we synthesize a series of castor oil based‐waterborne polyurethanes (CWPUs) with highly tunable properties by adjusting the content of 2,2‐dimethylolbutanoic acid (DMBA), a hydrophilic chain extender. The size of the polyurethane dispersions (PUDs) decreases from 120 nm to 20 nm, when DMBA content increases from 5 to 9 wt%. Infrared spectrum of the corresponding CWPUs films shows that the hydrogen bonds between hard segments have an enhancement as DMBA content increases. The thermal and mechanical properties of the CWPUs films have an obvious change due to this enhanced hydrogen bond interactions and behave like soft elastomer or rigid plastic. For example, the glass transition temperature (Tg) of the CWPUs films increases from 47.8 to 92.9 °C and meanwhile the tensile strength increases from 9.6 to 20.0 MPa. In addition, the CWPUs films are enzymatically hydrolysable due to the surface hydrophilicity. Importantly, those films exhibit excellent biocompatibility to mouse fibroblast (L‐929) cells and a relative cell viability of 76% compared to tissue culture polystyrene (TCPS) plates is obtained.

Practical applications: The synthesized CWPUs are versatile by change of the content of DMBA. The CWPUs can potentially replace wide range of part of petroleum‐based polymeric materials. In view of their good biodegradability and biocompatibility, the CWPUs are promising in biomedical applications.

Castor oil‐based waterborne polyurethanes show highly tunable properties and excellent biocompatibility, which are promising in on‐demand biomedical applications.
Catalytic valorization of oil‐derived fatty esters via cross‐metathesis with nitriles
Authors: Nieres Pablo D. , Zelin Juan , Trasarti Andrés F. , Apesteguía Carlos R.
Published: February 2016

The cross‐metathesis of methyl oleate with 3‐pentenenitrile to obtain 2‐undecene, methyl 9‐undecenoate, methyl 11‐cyano‐9‐undecenoate, and 3‐dodecenenitrile was studied at 323 K in a batch reactor using second‐generation Hoveyda–Grubbs (HG) catalysts. Self‐metathesis of methyl oleate was the main undesired secondary reaction. For a 3‐pentenenitrile/methyl oleate reactant ratio (R3PN/MO) of one, the yield () and selectivity () to cross‐metathesis products were 47 and 63%, respectively. The formation of cross‐metathesis products increased with increasing 3‐pentene initial concentrations, essentially because the reaction equilibrium was shifted to higher methyl oleate conversions. Thus, and were 74 and 83%, respectively, at R3PN/MO = 5. Nevertheless, the HG complex was significantly deactivated when high R3PN/MO values were employed.

Practical applications: Metathesis reactions are becoming increasingly attractive in the oleochemistry industry because they offer novel routes for the valorisation of unsaturated fatty acid methyl esters (FAME) that are cheap feedstocks obtained by transesterification of natural oils and fats. Recently, the cross‐metathesis of FAME with functionalized olefins such as esters, allylchlorides, and nitriles has been investigated to obtain renewable α,ω‐bifunctional compounds. In particular, the cross metathesis of nitriles with FAME constitutes an attractive synthesis route toward the production of useful polyamide precursors from natural renewable resources. In this work we investigate the cross‐metathesis of methyl oleate with 3‐pentenenitrile, an internal unsaturated nitrile that does not contain conjugated CC and CN bonds. The results presented in this work show that high yields (74%) and selectivities (88%) to cross‐metathesis products are obtained using the second‐generation Hoveyda–Grubbs Ru catalyst.

The cross‐metathesis of methyl oleate with 3‐pentenenitrile is studied using the second‐generation Hoveyda–Grubbs Ru complex as homogeneous catalyst. High yields (74%) and selectivities (88%) to cross‐metathesis products are obtained when pentenenitrile/methyl oleate ratios higher than 3 are employed.
Enantioselective Catalytic Domino Aza‐Michael–Henry Reactions: One‐Pot Asymmetric Synthesis of 3‐Nitro‐1,2‐dihydroquinolines via Iminium Activation
Authors: Luo Hao , Yan Xilong , Chen Ligong , Li Yang , Liu Na , Yin Guohui
Published: February 2016

Asymmetric transformations arising from iminium activation of aromatic aldehydes are uncommon. In this work, an enantioselective organocatalytic domino aza‐Michael–Henry reaction between N‐(2‐formylphenyl)sulfonamides and trans‐β‐nitro olefins through iminium activation has been presented. This reaction proceeded smoothly to give chiral 3‐nitro‐1,2‐dihydroquinolines in high yields with up to 88 % ee under mild conditions. Furthermore, a preliminary study showed that 2‐mercaptobenzaldehyde derivatives could participate in a thia‐Michael–Henry reaction with trans‐β‐nitro olefins to yield chiral 3‐nitro‐2H‐thiochromenes.
Catalytic Asymmetric Addition of Organolithium Reagents to Aldehydes
Authors: Veguillas Marcos , Solà Ricard , Shaw Luke , Maciá Beatriz
Published: February 2016

Herein we report an efficient catalytic system for the titanium‐promoted enantioselective addition of organolithium reagents to aldehydes, based on chiral Ar‐BINMOL ligands. Unprecedented yields and enantioselectivities are achieved in the alkylation reactions of aliphatic aldehydes. Remarkably, methyllithium can be added to a wide variety of aromatic and aliphatic aldehydes, providing versatile chiral methyl carbinol units in a simple one‐pot procedure under mild conditions and in very short reaction times.
Experimental pain sensitivity in multiple system atrophy and Parkinson's disease at an early stage
Authors: Mylius V. , Pee S. , Pape H. , Teepker M. , Stamelou M. , Eggert K. , Lefaucheur J‐P. , Oertel W.H. , Möller J. C.
Published: February 2016

Background

Chronic spontaneous pain is a clinically relevant non‐motor symptom in multiple system atrophy (MSA) and Parkinson's disease (PD). Experimental pain sensitivity, reflecting the mechanisms of nociception and pain perception leading to clinical pain, is known to be enhanced in both diseases at advanced stages. Also, this study aimed at investigating experimental pain sensitivity already at an early stage (i.e. symptom duration ≤5 years).

Methods

Experimental pain sensitivity was assessed by investigating the nociceptive flexion reflex (NFR, reflecting spinal nociception) and heat and electrical pain thresholds. ‘Off‐drug’ MSA (n = 11) and PD (n = 14) patients selected at an early stage of the disease were compared to healthy controls (HC, n = 27). MSA patients had either parkinsonian (MSA‐P, n = 5) or cerebellar (MSA‐C, n = 6) subtypes.

Results

Compared to HC, MSA patients had lower heat pain sensitivity, whereas PD patients had reduced NFR threshold. MSA and PD patients did not differ from HC regarding other variables. MSA‐P and MSA‐C patients did not differ, either.

Conclusions

Impaired sensory discrimination and attention deficits could contribute to the reduced perception of heat pain in MSA, whereas in PD, local changes in spinal excitability or a diminished dopaminergic descending inhibition might impact on the motor efference of the NFR to reduce its threshold to nociceptive afferent information.

What does this study add?

This study investigated experimental pain sensitivity at an early stage in MSA and PD.
Positive feedback regulation between microRNA‐132 and CREB in spinal cord contributes to bone cancer pain in mice
Authors: Hou B. , Cui X. , Liu Y. , Zhang W. , Liu M. , Sun Y.E. , Ma Z. , Gu X.
Published: February 2016

Background

cAMP response element‐binding protein (CREB)‐dependent gene expression plays an important role in central sensitization. CREB‐regulated transcription coactivator 1 (CRTC1) dramatically increase CREB‐mediated transcriptional activity. microRNA‐132 (miR‐132), which is highly CREB‐responsive, functions downstream from CREB/CRTC1 to mediate activity‐dependent synaptic plasticity and in turn loops back to amplify CREB/CRTC1 signalling. This study aimed to investigate the positive feedback regulation between miR‐132 and CREB in spinal cord in the maintenance of bone cancer pain.

Methods

Osteosarcoma cells were implanted into the intramedullary space of the right femurs of C3H/HeNCrlVr mice to induce bone cancer pain. We further investigated effects of repeated intrathecal administration with Adenoviruses expressing CREB‐siRNA or miR‐132 antisense locked nucleic acid (LNA), respectively, on nociceptive behaviours and on the activity of CREB/CRTC1 signalling.

Results

Intramedullary inoculation of osteosarcoma cells resulted in up‐regulation of spinal p‐CREB, CRTC1 and CREB‐target genes (NR2B and miR‐132). Repeated intrathecal administration with Adenoviruses expressing CREB‐siRNA or miR‐132 LNA‐AS, respectively, attenuated bone cancer‐evoked pain behaviours, reduced the activity of CREB/CRTC1 signalling and down‐regulated CREB‐target gene NR2B expression in spinal cord.

Conclusions

These findings suggest that activation of spinal CREB/CRTC1 signalling may play an important role in bone cancer pain. Interruption to the positive feedback regulation between CREB/CRTC1 and its target gene miR‐132 can effectively relieved the bone cancer‐induced mechanical allodynia and spontaneous pain.

What does this study add?

The positive feedback regulation between CREB/CRTC1 and its target gene miR‐132 in spinal cord plays an important role in bone cancer pain.
The prokineticin Bv8 sensitizes cutaneous terminals of female mice to heat
Authors: Hoffmann T. , Negri L. , Maftei D. , Lattanzi R. , Reeh P.W.
Published: February 2016

Background

Injection of the noxious peptide Bv8 has previously been shown to induce a biphasic thermal hyperalgesia in rodents, the first peak presumably due to peripheral sensitization. This hypothesis has never been directly confirmed. We have assessed whether Bv8 can indeed sensitize peripheral nerve fibres in the mouse to heat.

Methods

We used recordings from single cutaneous fibres, cutaneous calcitonin gene‐related peptide (CGRP) release and immunostaining in nerves and plantar skin to evaluate the Bv8 effects on cutaneous nerves.

Results

Application of Bv8 at nanomolar concentrations (30–310 nmol/L) to skin preparations significantly increased the heat‐induced discharge, the heat‐induced afterdischarge and reduced threshold temperature of single unmyelinated polymodal fibres. Furthermore, application of Bv8 to hind‐paw skin flaps or trigeminal ganglia significantly elevated their heat‐induced CGRP release. Capsaicin‐induced and to a lesser extent also KCl‐induced CGRP releases were also augmented after Bv8 treatment. Immunohistochemistry revealed co‐localization of prokineticin 2 (Bv8 ortholog in rodents) and CGRP in both plantar skin and nerve tissues. These results confirm that Bv8 sensitizes cutaneous nerve endings to heat, partly, although not exclusively through TRPV1 activation.

Conclusion

Our results thus support the hypothesis that the first hyperalgesic phase to follow Bv8 injection to hind paws of intact animals is due to peripheral sensitization of nociceptors.

What does this study add?

Our data provide mechanistic insights into the effect Bv8 application exerts on afferent nerve endings and into the concomitant development of thermal hyperalgesia.
Mesoporous Nitrogen‐Rich Carbon as Metal‐free Anode Catalyst for Borohydride Fuel Cells
Authors: Tiwari Aarti , Nagaiah Tharamani C.
Published: February 2016

A mesoporous carbon electrocatalyst rich in nitrogen was tested for its activity in borohydride electrochemical oxidation. This non‐noble, metal‐free, cost‐effective catalyst exhibits high current density and stability towards borohydride oxidation under highly alkaline conditions, even at elevated temperatures. The structure–activity relationship was also established for the differentially pyrolyzed mesoporous carbon electrocatalyst by electrochemical and physical characterization.
Development of a hybrid simulation controller for full‐scale experimental investigation of seismic retrofits for soft‐story woodframe buildings
Authors: Shao Xiaoyun , Pang Weichiang , Griffith Chelsea , Ziaei Ershad , van de Lindt John
Published: February 2016

Hybrid simulations of a full‐scale soft‐story woodframe building specimen with various retrofits were carried out as part of the Network for Earthquake Engineering Simulation Research project – NEES‐Soft: seismic risk reduction for soft‐story woodframe buildings. The test structure in the hybrid simulation was a three‐story woodframe building that was divided into a numerical substructure of the first story with various retrofits and a full‐scale physical substructure of the upper two stories. Four long‐stroke actuators, two at the second floor and two at the roof diaphragm, were attached to the physical substructure to impose the simulated seismic responses including both translation and in‐plane rotation. Challenges associated with this first implementation of a full‐scale hybrid simulation on a woodframe building were identified. This paper presents the development and validation of a scalable and robust hybrid simulation controller for efficient test site deployment. The development consisted of three incremental validation phases ranging from small‐scale, mid‐scale, to full‐scale tests conducted at three laboratories. Experimental setup, procedure, and results of each phase of the controller development are discussed, demonstrating the effectiveness and efficiency of the incremental controller development approach for large‐scale hybrid simulation programs with complex test setup. Copyright © 2016 John Wiley & Sons, Ltd.
Formation and erosion of sediment cover in an experimental bedrock‐alluvial channel
Authors: Hodge Rebecca , Hoey Trevor , Maniatis Georgios , Leprêtre Emilie
Published: February 2016

Sediment grains in a bedrock‐alluvial river will be deposited within or adjacent to a sediment patch, or as isolated grains on the bedrock surface. Previous analysis of grain geometry has demonstrated that these arrangements produce significant differences in grain entrainment shear stress. However, this analysis neglected potential interactions between the sediment patches, local hydraulics and grain entrainment. We present a series of flume experiments that measure the influence of sediment patches on grain entrainment. The flume had a planar bed with roughness that was much smaller than the diameters of the mobile grains. In each experiment sediment was added either as individual grains or as a single sediment pulse. Flow was then increased until the sediment was entrained. Analysis of the experiments demonstrates that: (1) for individual grains, coarse grains are entrained at a higher discharge than fine grains; (2) once sediment patches are present, the different in entrainment discharge between coarse and fine grains is greatly reduced; (3) the sheltering effect of patches also increases the entrainment discharge of isolated grains; (4) entire sediment patches break‐up and are eroded quickly, rather than through progressive grain‐by‐grain erosion; (5) as discharge increases there is some tendency for patches to become more elongate and flow‐aligned, and more randomly distributed across the bed. One implication of this research is that the critical shear stress in bedrock‐alluvial channels will be a function of the extent of the sediment cover. Another is that the influence of sediment patches equalizes critical shear stresses between different grain sizes and grain locations, meaning that these factors may not need to be accounted for. Further research is needed to quantify interactions between sediment patches, grain entrainment and local hydraulics on rougher bedrock surfaces, and under different types of sediment supply. Copyright © 2016 John Wiley & Sons, Ltd.
Effects of processing on carbendazim residue in Pleurotus ostreatus
Authors: Xia Erdong , Tao Wuqun , Yao Xi , Wang Jin , Tang Feng
Published: February 2016

Samples of Pleurotus ostreatus were exposed to fungicide carbendazim to study the effect of processing on the residues. In most cases, processing operations led to a significant decrease in residue levels in the finished products, particularly through washing, drying, and cooking processes. The results indicated that rinsing under running tap water led to more than 70.30% loss in carbendazim residues. When dried under sunlight could remove more than 70.30% residues. There was a 63.90–97.14% reduction after steaming, with processing time extending, the removal rates increased especially for lower initial residue level samples. The residue was almost completely removed by frying combined with microwave heating. Furthermore, boiling the mushrooms reduced the residue in the mushroom and no carbendazim residues were determined in the broth.
Establishment of proliferative tetraploid cells from telomerase‐immortalized normal human fibroblasts
Authors: Ohshima Susumu , Seyama Atsushi
Published: February 2016

Aneuploidy is observed in the majority of human cancers and is considered to be causally related to carcinogenesis. Although malignant aneuploid cells are suggested to develop from polyploid cells formed in precancerous lesions, the mechanisms of this process remain elusive. This is partly because no experimental model is available where nontransformed polyploid human cells propagate in vitro. We previously showed that proliferative tetraploid cells can be established from normal human fibroblasts by treatment with the spindle poison demecolcine (DC). However, the limited lifespan of these cells hampered detailed analysis of a link between chromosomal instability and the oncogenic transformation of polyploid cells. Here, we report the establishment of proliferative tetraploid cells from the telomerase‐immortalized normal human fibroblast cell line TIG‐1. Treatment of immortalized diploid cells with DC for 4 days resulted in proliferation of cells with tetraploid DNA content and near‐tetraploid/tetraploid chromosome counts. Established tetraploid cells had functional TP53 despite growing at almost the same rate as diploid cells. The frequency of clonal and sporadic chromosome aberrations in tetraploid cells was higher than in diploid cells and in one experiment, gradually increased with repeated subculture. This study suggests that tetraploid cells established from telomerase‐immortalized normal human fibroblasts can be a valuable model for studying chromosomal instability and the oncogenic potential of polyploid cells. © 2016 Wiley Periodicals, Inc.
No Place Like the Frontline: A Qualitative Study on What Participant CEOs Learned From Undercover Boss
Authors: Cumberland Denise M. , Alagaraja Meera
Published: February 2016

Through an inductive study of 13 CEOs participating in the reality television program Undercover Boss, we unravel senior leaders’ interactions with frontline employees focusing on what CEOs learned about their employees, themselves, and the direct effects of these interactions on HRD policies and practices. These vertical interactions helped CEOs institute more responsive HRD policies and practices, and address operational deficiencies on the frontline. A core contribution of this study is the identification of vertical interactions between senior leadership and frontline employees as a meaningful concept for HRD professionals to pursue. We encourage vertical interactions between CEO and frontline employees as an important mechanism for improving communication and information exchange, as well as a learning opportunity for the CEO. HRD professionals can play an important role in developing such interventions that can facilitate high‐quality exchanges between senior leaders and lower echelon employees. These interventions can help foster a positive climate and enhance employee morale, as well as improve the efficacy of HRD policies and practices.
Using the Bayesian network relative risk model risk assessment process to evaluate management alternatives for the South River and upper Shenandoah River, Virginia
Authors: Johns Annie F , Graham Scarlett E , Harris Meagan J , Markiewicz April J , Stinson Jonah M , Landis Wayne G
Published: February 2016

We have conducted a series of regional scale risk assessments using the Bayesian Network Relative Risk Model (BN-RRM) to evaluate the efficacy of 2 remediation options in the reduction of risks to the South River and upper Shenandoah River study area. The 2 remediation options were 1) bank stabilization (BST) and 2) the implementation of best management practices for agriculture (AgBMPs) to reduce Hg input in to the river. Eight endpoints were chosen to be part of the risk assessment, based on stakeholder input. Although Hg contamination was the original impetus for the site being remediated, multiple chemical and physical stressors were evaluated in this analysis. Specific models were built that incorporated the changes expected from AgBMP and BST and were based on our previous research. Changes in risk were calculated, and sensitivity and influence analyses were conducted on the models. The assessments indicated that AgBMP would only slightly change risk in the study area but that negative impacts were also unlikely. Bank stabilization would reduce risk to Hg for the smallmouth bass and belted kingfisher and increase risk to abiotic water quality endpoints. However, if care were not taken to prevent loss of nesting habitat to belted kingfisher, an increase in risk to that species would occur. Because Hg was only one of several stressors contributing to risk, the change in risk depended on the specific endpoint. Sensitivity analysis provided a list of variables to be measured as part of a monitoring program. Influence analysis provided the range of maximum and minimum risk values for each endpoint and remediation option. This research demonstrates the applicability of ecological risk assessment and specifically the BN-RRM as part of a long-term adaptive management scheme for managing contaminated sites. Integr Environ Assess Manag 2017;13:100–114. © 2016 SETAC

Key Points

It was possible to evaluate management alternatives in a risk assessment framework by estimating the changes in risk that may occur from these activities. In order to estimate the effectiveness of remediation strategies, it was necessary to include all of the relevant stressors and the endpoints in an assessment framework. The bank stabilization management option reduced risk to some endpoints, but careful planning is necessary to prevent introducing risk due to habitat loss. The uncertainty and sensitivity processes identified key variables for inclusion into a monitoring program to demonstrate the efficacy of the management options.
The Annulation of Nitrones and Donor‐Acceptor Cyclopropanes: A Personal Account of our Adventures to Date
Authors: Kerr Michael A.
Published: February 2016

This review is an account of our work in the development of the annulation reaction between nitrones and donor‐acceptor cyclopropanes. Methods development, mechanistic studies, and applications to total synthesis are discussed.
The use of substrate materials and topography to modify growth patterns and rates of differentiation of muscle cells
Authors: Murray L. M. , Nock V. , Evans J. J. , Alkaisi M. M.
Published: February 2016

Cells are cultured on platforms made of a variety of materials with selected topographies during studies of cell response and behavior. Understanding the effects of substrates is essential for such applications as developing effective interfaces between body cells and implanted materials and devices. In this study, the effects of substrate surface properties on cell differentiation and alignment on C2C12 myoblasts cultured on conventional or fabricated polymeric cell culture substrates were investigated. Comparisons were made between cells cultured on tissue culture grade polystyrene (TCPS), glass, Permanox, and cured polydimethylsiloxane (PDMS) substrates. Fluorescent immunohistochemistry of cell markers was used to analyse the extent of differentiation. Alignment and guidance of cell growth and spread were studied using patterned platforms. Gratings were made on polystyrene (PS) and PDMS and differentiation was facilitated after 5 days by media exchange. Differences in cell morphology were observed between cells cultured on TCPS and PDMS substrates. Fully differentiated myotubes were observed in highest numbers on TCPS substrates and were non‐detectable on PDMS substrates in the time frame of 144 h. Muscle cell alignment and their differentiation followed along the grating patterns on PS and elongated along the pattern length. On the other hand, on PDMS cells formed sheets of tissue and peeled from the substrate. We have revealed the potential for the combinations of surface materials and topography on cell behavior to induce accelerated differentiation and coordinated alignment. The results demonstrate that culture environment can be designed or engineered to modify or regulate muscle cell functions. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1638–1645, 2016.
Differential Regulation of Bcl‐xL Gene Expression by Corticosterone, Progesterone, and Retinoic Acid
Authors: Morrissy Steve J , Sun Haipeng , Zhang Jack , Strom Joshua , Chen Qin M.
Published: February 2016

Corticosterone (CT), progesterone (PG), and retinoic acid (RA) are capable of inhibiting Doxorubicin (Dox) from inducing apoptosis in rat cardiomyocytes. Mechanistically, CT, PG, and RA induce increases of Bcl‐xL protein and mRNA, and activate a 3.2 kb bcl‐x gene promoter. CT and RA, but not PG, induced the activity of a 0.9 kb bcl‐x promoter, containing sequences for AP‐1 and NF‐kB binding. RA, but not CT or PG, induced NF‐kB activation. CT, but not PG or RA, induced AP‐1 activation, and induction of the 0.9 kb bcl‐x reporter by CT was inhibited by dominant negative c‐Jun TAM‐67 or removal of AP‐1 binding site. Therefore, although CT, PG, and RA all induce Bcl‐xL mRNA and protein, three independent mechanisms are in operation: while CT induces Bcl‐xL via AP‐1 transcription factor, and RA induces NF‐kB activation and bcl‐x promoter activity, PG induces Bcl‐xL via a mechanism independent of NF‐kB or AP‐1.
Activity of ABCG2 Is Regulated by Its Expression and Localization in DHT and Cyclopamine‐Treated Breast Cancer Cells
Authors: Chua Vivian Y.L. , Larma Irma , Harvey Jennet , Thomas Marc A. , Bentel Jacqueline M.
Published: February 2016

Elevated expression of the efflux transporter, ATP‐binding cassette subfamily G isoform 2 (ABCG2) on the plasma membrane of cancer cells contributes to the development of drug resistance and is a key characteristic of cancer stem cells. In this study, gene expression analysis identified that treatment of the MCF‐7 and T‐47D breast cancer cell lines with the androgen, 5α‐dihydrotestosterone (DHT), and the Hedgehog signaling inhibitor, cyclopamine downregulated ABCG2 mRNA levels. In MCF‐7 cells, and in Hoechst 33342lo/CD44hi/CD24lo breast cancer stem‐like cells isolated from MCF‐7 cultures, ABCG2 was accumulated in cell‐to‐cell junction complexes and in large cytoplasmic aggresome‐like vesicles. DHT treatments, which decreased cellular ABCG2 protein levels, led to diminished ABCG2 localization in both cell‐to‐cell junction complexes and in cytoplasmic vesicles. In contrast, cyclopamine, which did not alter ABCG2 protein levels, induced accumulation of ABCG2 in cytoplasmic vesicles, reducing its localization in cell‐to‐cell junction complexes. The reduced localization of ABCG2 at the plasma membrane of MCF‐7 cells was associated with decreased efflux of the ABCG2 substrate, mitoxantrone, and increased sensitivity of cyclopamine‐treated cultures to the cytotoxic effects of mitoxantrone. Together, these findings indicate that DHT and cyclopamine reduce ABCG2 activity in breast cancer cells by distinct mechanisms, providing evidence to advocate the adjunct use of analogous pharmaceutics to increase or prolong the efficacy of breast cancer treatments. J. Cell. Biochem. 117: 2249–2259, 2016. © 2016 Wiley Periodicals, Inc.
Cancer Stem Cells Protect Non‐Stem Cells From Anoikis: Bystander Effects
Authors: Kim Seog‐Young , Hong Se‐Hoon , Basse Per H. , Wu Chuanyue , Bartlett David L. , Kwon Yong Tae , Lee Yong J.
Published: February 2016

Cancer stem cells (CSCs) are capable of initiation and metastasis of tumors. Therefore, understanding the biology of CSCs and the interaction between CSCs and their counterpart non‐stem cells is crucial for developing a novel cancer therapy. We used CSC‐like and non‐stem breast cancer MDA‐MB‐231 and MDA‐MB‐453 cells to investigate mammosphere formation. We investigated the role of the epithelial cadherin (E‐cadherin)‐extracellular signal‐regulated kinase (Erk) axis in anoikis. Data from E‐cadherin small hairpin RNA assay and mitogen‐activated protein kinase kinase (MEK) inhibitor study show that activation of Erk, but not modulation of E‐cadherin level, may play an important role in anoikis resistance. Next, the two cell subtypes were mixed and the interaction between them during mammosphere culture and xenograft tumor formation was investigated. Unlike CSC‐like cells, increased secretion of interleukin‐6 (IL‐6) and growth‐related oncogene (Gro) chemokines was detected during mammosphere culture in non‐stem cells. Similar results were observed in mixed cells. Interestingly, CSC‐like cells protected non‐stem cells from anoikis and promoted tumor growth. Our results suggest bystander effects between CSC‐like cells and non‐stem cells. J. Cell. Biochem. 117: 2289–2301, 2016. © 2016 Wiley Periodicals, Inc.
The Use of Dried Blood Spots for Pharmacokinetic Monitoring of Vemurafenib Treatment in Melanoma Patients
Authors: Nijenhuis Cynthia M. , Huitema Alwin D.R. , Marchetti Serena , Blank Christian , Haanen John B.A.G. , van Thienen Johannes V. , Rosing Hilde , Schellens Jan H.M. , Beijnen Jos H.
Published: February 2016

Pharmacokinetic monitoring is increasingly becoming an important part of clinical care of tyrosine kinase inhibitor treatment. Vemurafenib is an oral tyrosine kinase inhibitor that inhibits mutated serine/threonine protein kinase B‐Raf (BRAF) and is approved for the treatment of adult patients with BRAF V600 mutation‐positive unresectable or metastatic melanoma. The aim of this study was to establish the relationship between dried blood spot (DBS) and plasma concentrations of vemurafenib to enable the use of DBS sampling, which is a minimally invasive form of sample collection. In total, 43 paired plasma and DBS samples (in duplicate) were obtained from 8 melanoma patients on vemurafenib therapy and were analyzed using high‐performance liquid chromatography–tandem mass spectrometry. Plasma concentrations were predicted from the DBS concentrations using 2 methods: (1) individual hematocrit correction and blood cell‐to‐plasma partitioning and (2) the calculated slope explaining the relationship between DBS and plasma concentrations (without individual hematocrit correction). Vemurafenib DBS concentrations and plasma concentrations showed a strong correlation (r = 0.964), and the relationship could be described by ([vemurafenib]plasma = [vemurafenib]DBS/0.64). The predicted plasma concentrations were within ±20% of the analyzed plasma concentrations in 97% and 100% of the samples for the methods with and without hematocrit correction, respectively. In conclusion, DBS concentrations and plasma concentrations of vemurafenib are highly correlated. Plasma concentrations can be predicted from DBS concentration using the blood cell‐to‐plasma partition and the average hematocrit value of this cohort (0.40 L/L). DBS sampling for pharmacokinetic monitoring of vemurafenib treatment can be used in clinical practice.
Nutritional leucine supplementation attenuates cardiac failure in tumour‐bearing cachectic animals
Authors: Toneto Aline Tatiane , Ferreira Ramos Luiz Alberto , Salomão Emilianne Miguel , Tomasin Rebeka , Aereas Miguel Arcanjo , Gomes‐Marcondes Maria Cristina Cintra
Published: February 2016

Background

The condition known as cachexia presents in most patients with malignant tumours, leading to a poor quality of life and premature death. Although the cancer‐cachexia state primarily affects skeletal muscle, possible damage in the cardiac muscle remains to be better characterized and elucidated. Leucine, which is a branched chain amino acid, is very useful for preserving lean body mass. Thus, this amino acid has been studied as a coadjuvant therapy in cachectic cancer patients, but whether this treatment attenuates the effects of cachexia and improves cardiac function remains poorly understood. Therefore, using an experimental cancer‐cachexia model, we evaluated whether leucine supplementation ameliorates cachexia in the heart.

Methods

Male Wistar rats were fed either a leucine‐rich or a normoprotein diet and implanted or not with subcutaneous Walker‐256 carcinoma. During the cachectic stage (approximately 21 days after tumour implantation), when the tumour mass was greater than 10% of body weight, the rats were subjected to an electrocardiogram analysis to evaluate the heart rate, QT‐c, and T wave amplitude. The myocardial tissues were assayed for proteolytic enzymes (chymotrypsin, alkaline phosphatase, cathepsin, and calpain), cardiomyopathy biomarkers (myeloperoxidase, tissue inhibitor of metalloproteinases, and total plasminogen activator inhibitor 1), and caspase‐8, ‐9, ‐3, and ‐7 activity.

Results

Both groups of tumour‐bearing rats, especially the untreated group, had electrocardiography alterations that were suggestive of ischemia, dilated cardiomyopathy, and sudden death risk. Additionally, the rats in the untreated tumour‐bearing group but not their leucine‐supplemented littermates exhibited remarkable increases in chymotrypsin activity and all three heart failure biomarkers analysed, including an increase in caspase‐3 and ‐7 activity.

Conclusions

Our data suggest that a leucine‐rich diet could modulate heart damage, cardiomyocyte proteolysis, and apoptosis driven by cancer‐cachexia. Further studies must be conducted to elucidate leucine's mechanisms of action, which potentially includes the modulation of the heart's inflammatory process.
In vivo imaging of the spectral line broadening of the human lung in a single breathhold
Authors: Carinci Flavio , Meyer Cord , Breuer Felix A. , Jakob Peter M.
Published: February 2016

Purpose

To present a technique, which allows for the in vivo quantification of the spectral line broadening of the human lung in a single breathhold. The line broadening is an interesting parameter of the lung because it can provide information about important lung properties, namely: inflation and oxygen uptake. The proposed technique integrates the asymmetric spin‐echo (ASE) approach, which is commonly used to quantify the line broadening, with a single shot turbo spin‐echo pulse sequence with half‐Fourier acquisition (HASTE), to reduce the acquisition times.

Materials and Methods

Imaging experiments were performed at 1.5 Tesla on 14 healthy volunteers, using a ASE‐prepared HASTE sequence. The line broadening was quantified using a two‐points method. Data were acquired at different breathing states: functional residual capacity (FRC) and total lung capacity (TLC), and with different breathing gases: room‐air and pure‐oxygen. Image acquisition was accomplished within a single breathhold of approximately 15 s duration. The violation of the Carr‐Purcell‐Meiboom‐Gill conditions, deriving from inhomogeneities of the static magnetic field, was overcome by means of radiofrequency‐phase cycling and generalized autocalibrating partially parallel acquisitions (GRAPPA) reconstruction.

Results

Significant increase of the line broadening was observed with both lung inflation and oxygen concentration (P < 0.0001). Values of the line broadening obtained within the lung parenchyma at different breathing states (1.48 ± 0.29 ppm at FRC and 1.95 ± 0.43 ppm at TLC) are in agreement with previous reports and show excellent reproducibility, with a coefficient of variation <0.03. The mean relative difference observed with oxygen‐enhancement was approximately 14%.

Conclusion

The presented technique offers a robust way to quantify the spectral line broadening of the human lung in vivo. Image acquisition can be accomplished in a single breathhold, which could be suitable for clinical applications on patients with lung diseases. J. Magn. Reson. Imaging 2016;44:745–757.
Further studies on the role of the residue 890 cysteine to tyrosine mutation in the M70 primase ORF of the temperature‐sensitive mutant (tsm5) of murine cytomegalovirus
Authors: Al‐Ali Abdulaziz Taher , Sweet Clive
Published: February 2016

A mutation (C890Y) introduced into the M70 primase gene of murine cytomegalovirus (MCMV) resulted in reduced viral replication in murine embryo fibroblasts at 40°C and the mutant was severely attenuated in vivo. The attenuated replication of the M70 mutant was also observed in Raw 264.7 macrophages at 37°C, demonstrating that the mutation produced a defective rather than an unstable protein possibly reducing the amount of functional protein under different environmental conditions. Many synonymous mutations were introduced into this ORF by changing codon preferences that should reduce the efficiency of gene translation, but not change protein sequence or structure. Two Bacterial Artificial Chromosome (BAC) constructs were produced with 155 codons (at the distal third of the M70 gene) changed to MCMV less preferred codons and with either cysteine (BAC70155Cys) or tyrosine (BAC70155Tyr) at residue 890. Upon transfection of these BACs into NIH 3T3 cells, only BAC70155Cys produced virus and this mutant Mt70155Cys replicated similarly to its revertant and the wt MCMV K181 (Perth) variant. A metagenomic analysis of the protein structure of the primase using PredictProtein showed that the change from cysteine (M70Cys) to tyrosine (M70Tyr) has a marked effect on protein structure. However, when the cysteine residue was replaced by serine (M70Ser) or methionine (M70Met), which produced mutant viruses with a wild‐type phenotype, the predicted structure was similar to the wild‐type structure. J. Med. Virol. 88:1613–1621, 2016. © 2016 Wiley Periodicals, Inc.
Beyond the gut bacterial microbiota: The gut virome
Authors: Columpsi Paola , Sacchi Paolo , Zuccaro Valentina , Cima Serena , Sarda Cristina , Mariani Marcello , Gori Andrea , Bruno Raffaele
Published: February 2016

The gastrointestinal tract is colonized with a highly different population of bacterial, viral, ad fungal species; viruses are reported to be dominant. The composition of gut virome is closely related to dietary habits and surrounding environment. Host and their intestinal microbes live in a dynamic equilibrium and viruses stimulate a low degree of immune responses without causing symptoms (host tolerance). However, intestinal phages could lead to a rupture of eubiosis and may contribute to the shift from health to disease in humans and animals. Viral nucleic acids and other products of lysis of bacteria serve as pathogen‐associated molecular patterns (PAMPs) and could trigger specific inflammatory modulations. At the same time, phages could elicit innate antiviral immune responses. Toll‐like receptors (TLRs) operated as innate antiviral immune sensors and their activation triggers signaling cascades that lead to inflammatory response. J. Med. Virol. 88:1467–1472, 2016. © 2016 Wiley Periodicals, Inc.
Spread of regional climate model projections: vertical structure and temporal evolution
Authors: Holtanová Eva , Mikšovský Jiří
Published: February 2016

Due to imperfections inherent to numerical climate simulations, projections of climate change need to be accompanied with an uncertainty estimate, typically derived from multi‐model ensembles. Here, an analysis of regional climate model outputs spread and its temporal evolution is presented, for the European air temperatures simulated over the 21st century. To quantify the overall uncertainty, standard deviation (sd) is used and compared to median absolute deviation and inter‐quartile range. The outcomes are shown for annual and seasonal means of air temperature at 2 m, 850 hPa, 700 hPa, 500 hPa and 300 hPa levels, simulated by ENSEMBLES regional climate models for eight geographical areas across Europe. Our results indicate that the estimated uncertainty of simulated air temperature changes over Europe generally increases during the 21st century, and typically decreases with height of the studied vertical level. The influence of driving global climate model on the regional simulation generally increases with height of the studied vertical level. In lower tropospheric levels, the clustering of regional climate models according to driving global climate model is stronger in winter than in summer.
Phosphorus in forest ecosystems: New insights from an ecosystem nutrition perspective
Authors: Lang Friederike , Bauhus Jürgen , Frossard Emmanuel , George Eckhard , Kaiser Klaus , Kaupenjohann Martin , Krüger Jaane , Matzner Egbert , Polle Andrea , Prietzel Jörg , Rennenberg Heinz , Wellbrock Nicole
Published: February 2016

Phosphorus is one of the major limiting factors of primary productivity in terrestrial ecosystems and, thus, the P demand of plants might be among the most important drivers of soil and ecosystem development. The P cycling in forest ecosystems seems an ideal example to illustrate the concept of ecosystem nutrition. Ecosystem nutrition combines and extents the traditional concepts of nutrient cycling and ecosystem ecology. The major extension is to consider also the loading and unloading of nutrient cycles and the impact of nutrient acquiring and recycling processes on overall ecosystem properties. Ecosystem nutrition aims to integrate nutrient related aspects at different scales and in different ecosystem compartments including all processes, interactions and feedbacks associated with the nutrition of an ecosystem. We review numerous previous studies dealing with P nutrition from this ecosystem nutrition perspective. The available information contributes to the description of basic ecosystem characteristics such as emergence, hierarchy, and robustness. In result, we were able to refine Odum's hypothesis on P nutrition strategies along ecosystem succession to substrate related ecosystem nutrition and development. We hypothesize that at sites rich in mineral‐bound P, plant and microbial communities tend to introduce P from primary minerals into the biogeochemical P cycle (acquiring systems), and hence the tightness of the P cycle is of minor relevance for ecosystem functioning. In contrast, tight P recycling is a crucial emergent property of forest ecosystems established at sites poor in mineral bound P (recycling systems). We conclude that the integration of knowledge on nutrient cycling, soil science, and ecosystem ecology into holistic ecosystem nutrition will provide an entirely new view on soil–plant–microbe interactions.
Optimisation of pre‐drying and deep‐fat‐frying conditions for production of low‐fat fried carrot slices
Authors: Karacabey Erkan , Turan Merve S , Özçelik Şehriban G , Baltacıoğlu Cem , Küçüköner Erdoğan
Published: February 2016

BACKGROUND

The main objective of the current study was to reduce the fat content of fried carrot slices with a hot air pre‐drying step before frying. In this regard the effects of hot air drying and deep‐fat‐frying conditions on moisture and oil contents, breaking force and colour parameters of pre‐dried and fried carrot slices were investigated.

RESULTS

Statistical analysis with response surface methodology showed that there was a significant correlation between investigated responses and process variables (P ≤ 0.05). Based on the optimal conditions (63.4 °C for drying temperature, 16% for weight loss, 152 °C for frying temperature, and 207 s for frying time) produced by the optimisation of process conditions, more than 50% reduction in fat content of fried carrot slices was achieved by hot air pre‐drying before frying.

CONCLUSION

The results presented indicated that the proposed cooking method is useful to control final oil content of fried carrot slices, so indirectly limiting the daily calorie intake by consumers without spectacular losses in quality attributes. © 2016 Society of Chemical Industry
Modified properties of a glycated and cross‐linked soy protein isolate by transglutaminase and an oligochitosan of 5 kDa
Authors: Fu Miao , Zhao Xin‐Huai
Published: February 2016

BACKGROUND

Soy protein is an important protein ingredient for the food industry; however, its properties can be improved by enzymatic and chemical modifications. This study applied a new enzymatic glycation and cross‐linking to modify soy protein isolate (SPI), using an oligochitosan of 5 kDa and transglutaminase. Properties of the obtained glycated and cross‐linked SPI (GC‐SPI) were unknown and thus assessed.

RESULTS

GC‐SPI contained glucosamine of 13.6 g kg−1 protein, but less reactable &bond;NH2 than SPI (0.42 vs. 0.50 mol kg−1 protein). Infrared spectra and circular dichroism results showed that GC‐SPI other than SPI and cross‐linked SPI had more &bond;OH in molecules, and was more disordered in secondary structure. In comparison with SPI, GC‐SPI showed enhanced water‐binding capacity, could form aggregates with enlarged hydrodynamic radius (180.2 vs. 82.9 nm) and negative zeta‐potential (−31.2 vs. −27.7 mV) in dispersion, but exhibited lower thermal stability (e.g. greater mass loss) upon heating at a temperature above 288 °C. GC‐SPI also had lower in vitro proteolytic digestibility than SPI due to the protein cross‐linking.

CONCLUSION

Oligochitosan of 5 kDa and transglutaminase can be used to glycate and cross‐link SPI. This approach is applicable to generate potential protein ingredient with good hydration and dispersive stabilisation. © 2016 Society of Chemical Industry