bluuebunny/crossref_metadata_2025 huggingface dataset:
Site‐Specific Labeling of Proteins with a Chemically Stable, High‐Affinity Tag for Protein Study
Authors: Yang Yin , Li Qing‐Feng , Cao Chan , Huang Feng , Su Xun‐Cheng
Published: November 2012

Site‐specific labeling of proteins with paramagnetic lanthanides offers unique opportunities by virtue of NMR spectroscopy in structural biology. In particular, these paramagnetic data, generated by the anisotropic paramagnetism including pseudocontact shifts (PCS), residual dipolar couplings (RDC), and paramagnetic relaxation enhancement (PRE), are highly valuable in structure determination and mobility studies of proteins and protein–ligand complexes. Herein, we present a new way to label proteins in a site‐specific manner with a high‐affinity and chemically stable tag, 4‐vinyl(pyridine‐2,6‐diyl)bismethylenenitrilo tetrakis(acetic acid) (4VPyMTA), through thiol alkylation. Its performance has been demonstrated in G47C and E64C mutants of human ubiquitin both in vitro and in a crowded environment. In comparison with the published tags, 4VPyMTA has several interesting features: 1) it has a very high binding affinity for lanthanides (higher than EDTA), 2) there is no heterogeneity in complexes with lanthanides, 3) the derivatized protein is stable and potentially applicable to the in situ analysis of proteins.
Deep Desulfurization by Amphiphilic Lanthanide‐Containing Polyoxometalates in Ionic‐Liquid Emulsion Systems under Mild Conditions
Authors: Xu Junhua , Zhao Shen , Ji Yuanchun , Song Yu‐Fei
Published: November 2012

Amphiphilic lanthanide‐containing polyoxometalates (POMs) were prepared by surfactant encapsulation. Investigation of these lanthanide‐containing POMs in oxidative desulfurization (ODS) showed that highly efficient deep desulfurization could be achieved in only 14 min with 100 % conversion of dibenzothiophene under mild conditions by using (DDA)9LaW10/[omim]PF6 (DDA=dimethyldioctadecylammonium, omim=1‐octyl‐3‐methyl‐imidazolium) in the presence of H2O2. Furthermore, deep desulfurization proceeds smoothly in model oil with an S content as low as 50 ppm. A scaled‐up experiment in which the volume of model oil was increased from 5 to 1000 mL with S content of 1000 ppm indicated that about 99 % sulfur removal can be achieved in 40 mins in an ionic‐liquid emulsion system. To the best of our knowledge, the (DDA)9LaW10/[omim]PF6 catalyst system with H2O2 as oxidant is one of the most efficient desulfurization systems reported so far.
Direct Nucleophilic Addition to N‐Alkoxyamides
Authors: Yanagita Yuta , Nakamura Hugh , Shirokane Kenji , Kurosaki Yusuke , Sato Takaaki , Chida Noritaka
Published: November 2012

While the synthesis of amide bonds is now one of the most reliable organic reactions, functionalization of amide carbonyl groups has been a long‐standing issue due to their high stability. As an ongoing program aimed at practical transformation of amides, we developed a direct nucleophilic addition to N‐alkoxyamides to access multisubstituted amines. The reaction enabled installation of two different functional groups to amide carbonyl groups in one pot. The N‐alkoxy group played important roles in this reaction. First, it removed the requirement for an extra preactivation step prior to nucleophilic addition to activate inert amide carbonyl groups. Second, the N‐alkoxy group formed a five‐membered chelated complex after the first nucleophilic addition, resulting in suppression of an extra addition of the first nucleophile. While diisobutylaluminum hydride (DIBAL‐H) and organolithium reagents were suitable as the first nucleophile, allylation, cyanation, and vinylation were possible in the second addition including inter‐ and intramolecular reactions. The yields were generally high, even in the synthesis of sterically hindered α‐trisubstituted amines. The reaction exhibited wide substrate scope, including acyclic amides, five‐ and six‐membered lactams, and macrolactams.
New Reactivity of the Uranyl(VI) Ion
Authors: Baker Robert J.
Published: November 2012

The chemistry of the uranyl ion ([UO2]2+) has evolved remarkably over the past few years, with unexpected reactivity observed that challenge our understanding of this ion, and of actinides in general. This review highlights some recent advances in the field, focussing on the organometallic chemistry of the uranyl moiety, which is not well developed in comparison to lower oxidation states of uranium. The use of uranyl as a catalyst is highlighted and the newly developed supramolecular chemistry is described. The uranyl oxygen atoms have been considered as inert, but recent work has shown that is not necessarily the case and is discussed herein. Finally, reduction to the [UO2]+ ion will be discussed.
The Clinical Value of Echocardiography and Acoustic Cardiography to Monitor Patients Undergoing Anthracycline Chemotherapy
Authors: Toggweiler Stefan , Odermatt Yvonne , Brauchlin Andreas , Zander Thilo , Müller Andrea , Zuber Michel , Winterhalder Ralph , Erne Paul
Published: November 2012

Background

Investigate the usefulness of echocardiography and acoustic cardiography to monitor patients exposed to anthracycline chemotherapy.

Hypothesis

Serial echocardiographies to monitor systolic function may not be neccessary in all patients undergoing anthracycline chemotherapy.

Methods

In a prospective study, consecutive patients undergoing anthracycline‐containing chemotherapy were evaluated with echocardiography and acoustic cardiography at baseline, after completion of chemotherapy, and after a median follow‐up of 3.8 years. Systolic dysfunction was defined as a left ventricular ejection fraction ≤50%.

Results

A total of 187 patients (83% female) with a mean age of 55 ± 14 years underwent chemotherapy for breast cancer (73%), malignant lymphoma (23%), and sarcoma (4%). None of the patients had systolic dysfunction at baseline. Patients were treated with doxorubicin 276 ± 74 mg/m2 or epirubicin 317 ± 55 mg/m2. After chemotherapy, 170 (91%) had normal systolic function, 8 (4%) developed systolic dysfunction, and 9 (5%) had died. Of those 8 patients with systolic dysfunction, 4 (50%) improved to normal systolic function, 1 (13%) remained unchanged, and 3 (37%) died. Patients with normal systolic function after chemotherapy had a mortality rate of 3.5%, and 1.8% developed late systolic dysfunction. Acoustic cardiography‐derived percent electromechanical activation time >12.4% had a sensitivity of 88% and a specificity of 84% to identify patients with systolic dysfunction (area under the receiver operating characteristic curve 0.87).

Conclusions

Patients with systolic dysfunction early after anthracycline treatment had worse outcome. Acoustic cardiography was able to identify these patients with a high sensitivity and specificity. Based on the findings of this study, we propose a simple algorithm to monitor patients undergoing anthracycline‐containing chemotherapy.

The authors have no funding, financial relationships, or conflicts of interest to disclose.
Lysine‐directed staining of proteins for MS‐based analyses
Authors: Yasui Matthew T. , Mata‐Gómez Marco A. , Winkler Robert
Published: November 2012

Visualization of proteins and MS‐based analyses are elemental tasks in modern biochemistry. Nevertheless, reports about covalent protein dyes and their suitability for subsequent MS experiments remain scarce. In a recent work, we demonstrated that covalent prestaining of proteins with Uniblue A drastically speeds up proteomic workflows. The present study introduces dabsyl chloride as another truly MS‐compatible protein stain. Remarkably, although Uniblue A and dabsyl chloride employ different nucleophilic reaction mechanisms, both are highly specific for lysine residues. The predictable peptide modifications allow easy integration into state‐of‐the‐art bioinformatic workflows. Further, lysine‐directed derivatizations with hydrophobic reagents such as dabsyl chloride complement the cysteine‐directed ALiPHAT strategy for increasing the sensitivity of peptide identifications.
Logical circularity in voxel‐based analysis: Normalization strategy may induce statistical bias
Authors: Tustison Nicholas J. , Avants Brian B. , Cook Philip A. , Kim Junghoon , Whyte John , Gee James C. , Stone James R.
Published: November 2012

Recent discussions within the neuroimaging community have highlighted the problematic presence of selection bias in experimental design. Although initially centering on the selection of voxels during the course of fMRI studies, we demonstrate how this bias can potentially corrupt voxel‐based analyses. For such studies, template‐based registration plays a critical role in which a representative template serves as the normalized space for group alignment. A standard approach maps each subject's image to a representative template before performing statistical comparisons between different groups. We analytically demonstrate that in these scenarios the popular sum of squared difference (SSD) intensity metric, implicitly surrogating as a quantification of anatomical alignment, instead explicitly maximizes effect size—an experimental design flaw referred to as “circularity bias.” We illustrate how this selection bias varies in strength with the similarity metric used during registration under the hypothesis that while SSD‐related metrics, such as Demons, will manifest similar effects, other metrics which are not formulated based on absolute intensity differences will produce less of an effect. Consequently, given the variability in voxel‐based analysis outcomes with similarity metric choice, we caution researchers specifically in the use of SSD and SSD‐related measures where normalization and statistical analysis involve the same image set. Instead, we advocate a more cautious approach where normalization of the individual subject images to the reference space occurs through corresponding image sets which are independent of statistical testing. Alternatively, one can use similarity terms that are less sensitive to this bias. Hum Brain Mapp 35:745–759, 2014. © 2012 Wiley Periodicals, Inc.
Regionally specific increased volume of the amygdala in Williams syndrome: Evidence from surface‐based modeling
Authors: Haas Brian W. , Sheau Kristen , Kelley Ryan G. , Thompson Paul M. , Reiss Allan L.
Published: November 2012

Williams syndrome (WS) is a condition caused by a contiguous deletion of approximately 26–28 genes from chromosome 7, and is characterized by abnormal social and emotional processing and abnormal structure and function of the amygdala. Prior studies show that the amygdala is relatively enlarged in WS, but very little is known regarding the regional specificity of increased amygdalar volume in this condition. Here we investigated the regional specificity of structural alterations of the amygdala in WS, compared to a typically developing (TD) control group. We acquired high resolution brain MRI data from 79 participants (39 WS, 40 TD) and used a surface‐based analytical modeling approach. The WS group exhibited several areas of increased radial expansion of the amygdalar surface and no areas of decreased radial expansion of the amygdalar surface compared to TD controls. The areas found to exhibit particularly increased radial expansion in WS included the bilateral posterior cortical nucleus, lateral nucleus, and the central nucleus. This greater regional and anatomical specificity of altered amygdala structure in WS contributes to a model relating genetic risk in WS to the development of key brain regions for social and emotional functioning. Hum Brain Mapp 35:866–874, 2014. © 2012 Wiley Periodicals, Inc.
Contrast-enhanced intraoperative ultrasonography for vascular imaging of hepatocellular carcinoma: Clinical and biological significance
Authors: Sato Kota , Tanaka Shinji , Mitsunori Yusuke , Mogushi Kaoru , Yasen Mahmut , Aihara Arihiro , Ban Daisuke , Ochiai Takanori , Irie Takumi , Kudo Atsushi , Nakamura Noriaki , Tanaka Hiroshi , Arii Shigeki
Published: November 2012

Abnormal tumor vascularity is one of the typical features of hepatocellular carcinoma (HCC). In this study, the significance of contrast-enhanced intraoperative ultrasonography (CEIOUS) images of HCC vasculature was evaluated by clinicopathological and gene expression analyses. We enrolled 82 patients who underwent curative hepatic resection for HCC with CEIOUS. Clinicopathological and gene expression analyses were performed according to CEIOUS vasculature patterns. CEIOUS images of HCC vasculatures were classified as reticular HCC or thunderbolt HCC. Thunderbolt HCC was significantly correlated with higher alpha-fetoprotein levels, tumor size, histological differentiation, portal vein invasion, and tumor-node-metastasis stage, and these patients demonstrated a significantly poorer prognosis for both recurrence-free survival (

P

= 0.0193) and overall survival (

P

= 0.0362) compared with patients who had reticular HCC. Gene expression analysis revealed that a rereplication inhibitor geminin was significantly overexpressed in thunderbolt HCCs (

P

= 0.00326).

In vitro

knockdown of geminin gene reduced significantly the proliferation of human HCC cells. Immunohistochemical analysis confirmed overexpression of geminin protein in thunderbolt HCC (

P

< 0.0001). Multivariate analysis revealed geminin expression to be an independent factor in predicting poor survival in HCC patients (

P

= 0.0170).

Conclusion

: CEIOUS vascular patterns were distinctly identifiable by gene expression profiling associated with cellular proliferation of HCC and were significantly related to HCC progression and poor prognosis. These findings might be clinically useful as a determinant factor in the postoperative treatment of HCC.
A conformational heparan sulfate binding site essential to infectivity overlaps with the conserved hepatitis B virus A-determinant
Authors: Sureau Camille , Salisse Jessica
Published: November 2012

Two determinants of infectivity have been identified in the hepatitis B virus (HBV) envelope proteins: a pre-S1 receptor-binding site and an uncharacterized determinant in the antigenic loop (AGL), which is structurally related to the antigenic a-determinant. Infection would proceed through virus attachment to cell surface heparan sulfate (HS) proteoglycans (HSPGs) before pre-S1 engages a specific receptor for uptake. Using heparin binding and

in vitro

infection assays with hepatitis D virus as a surrogate for HBV, we established that HS binding is mediated by the AGL. Electrostatic interaction was shown to depend upon AGL residues R122 and K141, because their substitution with alanine modified the virus net-charge and prevented binding to heparin, attachment to hepatocytes, and infection. In addition to R122 and K141, the HS binding determinant was mapped to cysteines and prolines, which also define the conformational a-determinant. The importance of AGL conformation was further demonstrated by the concomitant loss of a-determinant and heparin binding upon treatment of viral particles with membrane-impermeable reducing agent. Furthermore, envelope proteins extracted from the viral membrane with a nonionic detergent were shown to conserve the a-determinant but to lose heparin affinity/avidity.

Conclusion
: Our findings support a model in which attachment of HBV to HSPGs is mediated by the AGL HS binding site, including only two positively charged residues (R122 and K141) positioned precisely in a three-dimensional AGL structure that is stabilized by disulfide bonds. HBV envelope proteins would individually bind to HS with low affinity, but upon their clustering in the viral membrane, they would reach sufficient avidity for a stable interaction between virus and cell surface HSPGs. Our data provide new insight into the HBV entry pathway, including the opportunity to design antivirals directed to the AGL-HS interaction. (Hepatology 2013)
Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma
Authors: Wang Xijun , Zhang Aihua , Sun Hui
Published: November 2012

Hepatocellular carcinoma (HCC) is the commonest primary hepatic malignancy and the third most common cause of cancer-related death worldwide. Incidence remains highest in the developing world and is steadily increasing across the developed world. Current diagnostic modalities, of ultrasound and α-fetoprotein, are expensive and lack sensitivity in tumor detection. Because of its asymptomatic nature, HCC is usually diagnosed at late and advanced stages, for which there are no effective therapies. Thus, biomarkers for early detection and molecular targets for treating HCC are urgently needed. Emerging high-throughput metabolomics technologies have been widely applied, aiming at the discovery of candidate biomarkers for cancer staging, prediction of recurrence and prognosis, and treatment selection. Metabolic profiles, which are affected by many physiological and pathological processes, may provide further insight into the metabolic consequences of this severe liver disease. Small-molecule metabolites have an important role in biological systems and represent attractive candidates to understand HCC phenotypes. The power of metabolomics allows an unparalleled opportunity to query the molecular mechanisms of HCC. This technique-driven review aims to demystify the metabolomics pathway, while also illustrating the potential of this technique, with recent examples of its application in HCC.
Chimeric hepatitis B virus/hepatitis C virus envelope proteins elicit broadly neutralizing antibodies and constitute a potential bivalent prophylactic vaccine
Authors: Beaumont Elodie , Patient Romuald , Hourioux Christophe , Dimier-Poisson Isabelle , Roingeard Philippe
Published: November 2012

The development of a prophylactic vaccine against hepatitis C virus (HCV) has become an important medical priority, because 3-4 million new HCV infections are thought to occur each year worldwide. Hepatitis B virus (HBV) is another major human pathogen, but infections with this virus can be prevented with a safe, efficient vaccine, based on the remarkable ability of the envelope protein (S) of this virus to self-assemble into highly immunogenic subviral particles. Chimeric HBV-HCV envelope proteins in which the N-terminal transmembrane domain of S was replaced with the transmembrane domain of the HCV envelope proteins (E1 or E2) were efficiently coassembled with the wild-type HBV S protein into subviral particles. These chimeric particles presented the full-length E1 and E2 proteins from a genotype 1a virus in an appropriate conformation for formation of the E1-E2 heterodimer. Produced in stably transduced Chinese hamster ovary cells and used to immunize New Zealand rabbits, these particles induced a strong specific antibody (Ab) response against the HCV and HBV envelope proteins in immunized animals. Sera containing anti-E1 or anti-E2 Abs elicited by these particles neutralized infections with HCV pseudoparticles and cell-cultured viruses derived from different heterologous 1a, 1b, 2a, and 3 strains. Moreover, the anti–hepatitis B surface response induced by these chimeric particles was equivalent to the response induced by a commercial HBV vaccine.

Conclusions:

Our results provide support for approaches based on the development of bivalent HBV-HCV prophylactic vaccine candidates potentially able to prevent initial infection with either of these two hepatotropic viruses.
An investigation of risk factors for renal cell carcinoma by histologic subtype in two case‐control studies
Authors: Purdue Mark P. , Moore Lee E. , Merino Maria J. , Boffetta Paolo , Colt Joanne S. , Schwartz Kendra L. , Bencko Vladimir , Davis Faith G. , Graubard Barry I. , Janout Vladimir , Ruterbusch Julie J. , Beebe‐Dimmer Jennifer , Cote Michele L. , Shuch Brian , Mates Dana , Hofmann Jonathan N. , Foretova Lenka , Rothman Nathaniel , Szeszenia‐Dabrowska Neonilia , Matveev Vsevolod , Wacholder Sholom , Zaridze David , Linehan W. Marston , Brennan Paul , Chow Wong‐Ho
Published: November 2012

To investigate whether renal cell carcinoma (RCC) histologic subtypes possess different etiologies, we conducted analyses of established RCC risk factors by subtype (clear cell, papillary and chromophobe) in two case‐control studies conducted in the United States (1,217 cases, 1,235 controls) and Europe (1,097 cases, 1,476 controls). Histology was ascertained for 706 U.S. cases (58% of total) and 917 European cases (84%) through a central slide review conducted by a single pathologist. For the remaining cases, histology was abstracted from the original diagnostic pathology report. Case‐only analyses were performed to compute odds ratios (ORs) and 95% confidence intervals (CI) summarizing subtype differences by age, sex and race. Case‐control analyses were performed to compute subtype‐specific ORs for other risk factors using polytomous regression. In case‐only analyses, papillary cases (N = 237) were older (OR = 1.2, 95% CI = 1.1–1.4 per 10‐year increase), less likely to be female (OR = 0.5, 95% CI = 0.4–0.8) and more likely to be black (OR = 2.6, 95% CI = 1.8–3.9) as compared to clear cell cases (N = 1,524). In case‐control analyses, BMI was associated with clear cell (OR = 1.2, 95% CI = 1.1–1.3 per 5 kg/m2 increase) and chromophobe RCC (N = 80; OR = 1.2, 95% CI = 1.1–1.4), but not papillary RCC (OR = 1.1, 95% CI = 1.0–1.2; test versus clear cell, p = 0.006). No subtype differences were observed for associations with smoking, hypertension or family history of kidney cancer. Our findings support the existence of distinct age, sex and racial distributions for RCC subtypes, and suggest that the obesity‐RCC association differs by histology.
The dual PI3K/mTOR inhibitor NVP‐BEZ235 and chloroquine synergize to trigger apoptosis via mitochondrial‐lysosomal cross‐talk
Authors: Seitz Christian , Hugle Manuela , Cristofanon Silvia , Tchoghandjian Aurélie , Fulda Simone
Published: November 2012

On the basis of our previous identification of aberrant phosphatidylinositol‐3‐kinase (PI3K)/Akt signaling as a novel poor prognostic factor in neuroblastoma, we evaluated the dual PI3K/mTOR inhibitor BEZ235 in the present study. Here, BEZ235 acts in concert with the lysosomotropic agent chloroquine (CQ) to trigger apoptosis in neuroblastoma cells in a synergistic manner, as calculated by combination index (CI < 0.5). Surprisingly, inhibition of BEZ235‐induced autophagy is unlikely the primary mechanism of this synergism as reported in other cancers, since neither inhibition of autophagosome formation by knockdown of Atg7 or Atg5 nor disruption of the autophagic flux by Bafilomycin A1 (BafA1) enhance BEZ235‐induced apoptosis. BEZ235 stimulates enlargement of the lysosomal compartment and generation of reactive oxygen species (ROS), while CQ promotes lysosomal membrane permeabilization (LMP). In combination, BEZ235 and CQ cooperate to trigger LMP, Bax activation, loss of mitochondrial membrane potential (MMP) and caspase‐dependent apoptosis. Lysosome‐mediated apoptosis occurs in a ROS‐dependent manner, as ROS scavengers significantly reduce BEZ235/CQ‐induced loss of MMP, LMP and apoptosis. There is a mitochondrial‐lysosomal cross‐talk, since lysosomal enzyme inhibitors significantly decrease BEZ235‐ and CQ‐induced drop of MMP and apoptosis. In conclusion, BEZ235 and CQ act in concert to trigger LMP and lysosome‐mediated apoptosis via a mitochondrial‐lysosomal cross‐talk. These findings have important implications for the rational development of PI3K/mTOR inhibitor‐based combination therapies.
Activation of the human immune system via toll‐like receptors by the oncolytic parvovirus H‐1
Authors: Sieben Maike , Schäfer Petra , Dinsart Christiane , Galle Peter R. , Moehler Markus
Published: November 2012

This study aimed to investigate the function of toll‐like receptors (TLRs) during oncolytic parvovirus H‐1 (H‐1PV)‐induced human immune responses. First, the role of TLRs in the activation of the NFκB transcription factor was characterized; second, the immunologic effects of H‐1PV‐induced tumor cell lysates (TCL) on human antitumor immune responses were evaluated. A human ex vivo model was used to study immune responses with dendritic cells (DCs). Human embryonic kidney cells (HEK293) transfected to stably express TLRs were used as potential human DC equivalents to further investigate the role of specific TLRs during immune activation. TLR3 and TLR9 were activated by H‐1PV infection, which correlated with NFκB translocation to the nucleus and a reduced cytoplasmic IκB expression. Using a TLR‐signaling reporter plasmid (pNiFty‐Luc), NFκB activity was increased following H‐1PV infection. In addition, human DCs coincubated with H‐1PV‐induced TCL demonstrated increased TLR3 and TLR9 expression. These data suggest that H‐1PV‐induced TCL stimulate human DCs at least in part through TLR‐dependent signaling pathways. Thus, DC maturation occurred through exposure to H‐1PV‐induced TCL through TLR‐signaling leading to NFκB‐dependent activation of the adaptive immune system as indicated by the increased expression of CD86, TLR3 and TLR9. Furthermore, the transcription of various cytokines indicates the activation of immune response, therefore the production of the proinflammatory cytokine TNF‐α was determined. Here, H‐1PV‐induced TCL significantly enhanced the TNF‐α level by DCs after coculture. H‐1PV oncolytic virotherapy enhances immune priming by different effects on DCs and generates antitumor immunity. These findings potentially offer a new approach to tumor therapy.
Biomimetic hydroxyapatite coating on pore walls improves osteointegration of poly(L‐lactic acid) scaffolds
Authors: Deplaine H. , Lebourg M. , Ripalda P. , Vidaurre A. , Sanz‐Ramos P. , Mora G. , Prósper F. , Ochoa I. , Doblaré M. , Gómez Ribelles J. L. , Izal‐Azcárate I. , Gallego Ferrer G.
Published: November 2012

Polymer–ceramic composites obtained as the result of a mineralization process hold great promise for the future of tissue engineering. Simulated body fluids (SBFs) are widely used for the mineralization of polymer scaffolds. In this work an exhaustive study with the aim of optimizing the mineralization process on a poly(L‐lactic acid) (PLLA) macroporous scaffold has been performed. We observed that when an air plasma treatment is applied to the PLLA scaffold its hydroxyapatite nucleation ability is considerably improved. However, plasma treatment only allows apatite deposition on the surface of the scaffold but not in its interior. When a 5 wt % of synthetic hydroxyapatite (HAp) nanoparticles is mixed with PLLA a more abundant biomimetic hydroxyapatite layer grows inside the scaffold in SBF. The morphology, amount, and composition of the generated biomimetic hydroxyapatite layer on the pores' surface have been analyzed. Large mineralization times are harmful to pure PLLA as it rapidly degrades and its elastic compression modulus significantly decreases. Degradation is retarded in the composite scaffolds because of the faster and extensive biomimetic apatite deposition and the role of HAp to control the pH. Mineralized scaffolds, covered by an apatite layer in SBF, were implanted in osteochondral lesions performed in the medial femoral condyle of healthy sheep. We observed that the presence of biomimetic hydroxyapatite on the pore's surface of the composite scaffold produces a better integration in the subchondral bone, in comparison to bare PLLA scaffolds. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 173–186, 2013.
Mixed algae cultures for low cost environmental compensation in cultures grown for lipid production and wastewater remediation
Authors: Johnson Kyle R , Admassu Wudneh
Published: November 2012

Background

Most cultures of algae today are grown as monocultures. The primary reason for this appears to be that specific strains of algae contain the high‐value products that are desired for harvest. But, in algae cultures grown primarily for lipid production, or as a stage in wastewater remediation, mixed algae cultures may mitigate environmental risk.

Results

Four‐strain mixed cultures of algae were grown in simulated wastewater, alongside the monocultures, under different temperature and lighting conditions. Under all conditions the mixed cultures were less productive than the most fit monocultures for each situation, but more productive than the least fit monocultures. Statistical analysis based on an exponential growth model of the monocultures also suggested that mixed cultures are actually more productive both in terms of biomass and lipids than simply the sum of the monocultures.

Conclusuions

A mixed culture composed of various similarly productive strains with various optimal growing conditions would be less susceptible to environmental shifts than a monoculture. This study demonstrated the promise of an appropriately defined mixed culture to reduce risk in applications such as wastewater remediation and lipid production that do not rely on specific strains containing high value products. © 2012 Society of Chemical Industry
Invasive biomass valorization: environmentally friendly processes for obtaining second generation bioethanol and saccharides from Ulex europæus
Authors: Ares‐Peón Iria Ana , Romaní Aloia , Garrote Gil , Parajó Juan Carlos
Published: November 2012

BACKGROUND

Ulex europæus (UE) is a widespread
invasive shrub species causing economic problems and environmental
hazards. This work deals with the valorization of UE by
hydrothermal processing (to obtain hemicelluloses‐derived
saccharides) followed by simultaneous saccharification and fermentation of the resulting solids for manufacturing second generation bioethanol.

RESULTS

Hydrothermal processing of UE resulted in the
solubilization of up to 21.5 wt% of the oven‐dry raw
material, leading to the formation of hemicelluloses‐derived
saccharides as major reaction products. Treatments at various
severities resulted in processed solids with enhanced susceptibility to enzymatic hydrolysis, allowing cellulose to glucose conversions up to 87%. Simultaneous saccharification and fermentation of solids pretreated under selected conditions, performed at various charges and solid loadings, resulted in bioethanol conversions up to 82% of the stoichiometric amount, with volumetric concentrations higher than 30 g ethanol L‐1.

CONCLUSION

Hydrothermal processing of UE followed by simultaneous
saccharification and fermentation of pretreated solids was suitable
for the selective separation of hemicelluloses as soluble saccharides
and for the manufacture of second generation bioethanol at high yield
from the pretreated solids.© 2012 Society of Chemical Industry
Endometrial cancer: Utility of diffusion‐weighted magnetic resonance imaging with background body signal suppression at 3T
Authors: Seo Jung Min , Kim Chan Kyo , Choi Dongil , Kwan Park Byung
Published: November 2012

Purpose:

To prospectively assess the usefulness of diffusion‐weighted magnetic resonance imaging (MRI) with background body signal suppression (DWIBS) at 3T for the preoperative evaluation of endometrial cancer.

Materials and Methods:

Fifty‐two consecutive patients with biopsy‐proven endometrial cancer were examined with a 3T MR scanner, followed by a hysterectomy. MR examinations included T2‐weighted (T2WI), DWIBS, and dynamic contrast‐enhanced T1‐weighted imaging (DCEI). The apparent diffusion coefficient (ADC) was calculated in the tumor and normal myometrium. According to tumor grade, the mean ADC of the tumor was analyzed. The depth of myometrial invasion was independently assessed by two radiologists for three MRI datasets on a five‐point scale.

Results:

The mean ADC of the tumors was significantly lower than that of normal myometrium (P < 0.001). The mean ADC of grades 2 or 3 was significantly lower than grade 1 (P < 0.01). For predicting myometrial invasion, the specificity, accuracy, and area under the curve of combined T2WI and DWIBS in both readers were similar to DCEI (P > 0.05). Interreader agreement in all MRI datasets was excellent.

Conclusion:

DWIBS at 3T has potential for being an effective method for the preoperative evaluation of endometrial cancer. J. Magn. Reson. Imaging 2013;37:1151–1159. © 2012 Wiley Periodicals, Inc.
Subject tolerance of 7 T MRI examinations
Authors: Versluis Maarten J. , Teeuwisse Wouter M. , Kan Hermien E. , van Buchem Mark A. , Webb Andrew G. , van Osch Matthias J.
Published: November 2012

Purpose:

To determine the subjective experiences and the sources of discomfort for subjects undergoing 7 T magnetic resonance imaging (MRI) examinations on a whole‐body 7 T system in a hospital setting

Materials and Methods:

A postscan survey was filled out by 101 healthy subjects who participated in a 7 T examination. All participants answered questions regarding different potential sensations of discomfort including dizziness, claustrophobia, and scanner noise.

Results:

Dizziness was reported most frequently, with 34% of subjects experiencing dizziness while moving into the scanner and 30% while moving out of the magnet. Scanner noise was also frequently mentioned as uncomfortable (33% of the subjects). In 11% of the cases a metallic taste was reported. The overall experience was rated by 3% as unpleasant, 51% as neutral, and 46% as pleasant.

Conclusion:

The reported side effects are larger than previously reported for lower field strengths. However, overall, 7 T examinations are well tolerated, with only 3% of subjects rating it as unpleasant. These results agree well with previous in‐depth studies, and provide further evidence that 7 T MRI would be accepted by patients in clinical practice. J. Magn. Reson. Imaging 2013;38:722–725. © 2012 Wiley Periodicals, Inc.
Corticomedullary differentiation of the kidney: Evaluation with noncontrast‐enhanced steady‐state free precession (SSFP) MRI with time‐spatial labeling inversion pulse (time‐SLIP)
Authors: Kanki Akihiko , Ito Katsuyoshi , Tamada Tsutomu , Noda Yasufumi , Yamamoto Akira , Tanimoto Daigo , Sato Tomohiro , Higaki Atsushi
Published: November 2012

Purpose:

To assess whether noncontrast‐enhanced steady‐state free precession (SSFP) magnetic resonance imaging (MRI) with time‐spatial labeling inversion pulse (Time‐SLIP) can improve the visibility of corticomedullary differentiation of the normal kidney.

Materials and Methods:

A series of noncontrast‐enhanced SSFP MRI with Time‐SLIP were performed in 20 patients by using various inversion times (TIs); 500–1800 msec in increments of 100 msec. In‐phase (IP) and opposed‐phase (OP) MR images were also obtained. The signal intensity (SI) of the renal cortex and medulla was measured to calculate corticomedullary contrast ratio (SI of cortex/medulla). Additionally, the visibility of corticomedullary differentiation was visually categorized using a four‐point scale.

Results:

In SSFP with Time‐SLIP, corticomedullary contrast ratio was highest with TI of 1200 msec in eight subjects (40%), followed by 1100 msec in seven (35%) and 1000 msec in three (15%). The corticomedullary contrast ratio in SSFP with optimal Time‐SLIP (4.93 ± 1.25) was significantly higher (P < 0.001) than those of IP (1.46 ± 0.12) and OP (1.43 ± 0.14). The visibility of corticomedullary differentiation was significantly better (P < 0.001) in SSFP images with Time‐SLIP (averaged grade = 4.0) than in IP images (averaged grade = 2.63) and OP images (averaged grade = 2.05).

Conclusion:

SSFP MRI with Time‐SLIP can improve the visibility of renal corticomedullary differentiation without using contrast agents. J. Magn. Reson. Imaging 2012;37:1178–1181. © 2012 Wiley Periodicals, Inc.
Impaired hypoxic sensor Siah‐1, PHD3, and FIH system in spinal motor neurons of an amyotrophic lateral sclerosis mouse model
Authors: Sato Kota , Morimoto Nobutoshi , Kurata Tomoko , Mimoto Takafumi , Miyazaki Kazunori , Ikeda Yoshio , Abe Koji
Published: November 2012

We recently reported spinal blood flow–metabolism uncoupling in the Cu/Zn‐superoxide dismutase 1 (SOD1)‐transgenic (Tg) mouse model of amyotrophic lateral sclerosis (ALS), suggesting relative hypoxia in the spinal cord. However, the hypoxic stress sensor pathway in ALS has not been well studied. In the present work, we examined the temporal and spatial changes of hypoxic stress sensor proteins (Siah‐1, PHD3, and FIH) following motor neuron (MN) degeneration in the spinal cord of normoxic ALS mice. The expression of Siah‐1 and PHD3 proteins progressively increased in the surrounding glial cells of presymptomatic Tg mice (10 weeks, 10 weeks) compared with the large MN of the anterior horn. In contrast, a significant reduction in Siah‐1 and PHD3 protein expression was evident in end‐stage ALS mice (18 weeks, 18 weeks). Double‐immunofluorescence analysis revealed PHD3 plus Siah‐1 double‐positive cells in the surrounding glia of symptomatic Tg mice (14–18 weeks), with no change in the large MNs. In contrast, FIH protein expression decreased in the surrounding glial cells of Tg mice at end‐stage ALS (18 weeks). The present study suggests a partial loss in the neuroprotective response of spinal MNs in ALS results from a relative hypoxia through the Siah‐1, PHD3, and FIH system under normoxic conditions. This response could be an important mechanism of neurodegeneration in ALS. © 2012 Wiley Periodicals, Inc.
N‐methyl‐D‐aspartate receptor‐mediated axonal injury in adult rat corpus callosum
Authors: Zhang Jingdong , Liu Jianuo , Fox Howard S. , Xiong Huangui
Published: November 2012

Damage to white matter such as corpus callosum (CC) is a pathological characteristic in many brain disorders. Glutamate (Glut) excitotoxicity through AMPA receptors on oligodendrocyte (OL) was previously considered as a mechanism for white matter damage. Recent studies have shown that N‐methyl‐D‐aspartate receptors (NMDARs) are expressed on myelin sheath of neonatal rat OL processes and that activation of these receptors mediated demyelization. Whether NMDARs are expressed in the adult CC and are involved in excitotoxic axonal injury remains to be determined. In this study, we demonstrate the presence of NMDARs in the adult rat CC and their distributions in myelinated nerve fibers and OL somata by means of immunocytochemical staining and Western blot. Incubation of the CC slices with Glut or NMDA induced axonal injury as revealed by analyzing amplitude of CC fiber compound action potentials (CAPs) and input–output response. Both Glut and NMDA decreased the CAP amplitude and input–output responses, suggesting an involvement of NMDARs in Glut‐ and NMDA‐induced axonal injury. The involvement of NMDAR in Glut‐induced axonal injury was further assayed by detection of β‐amyloid precursor protein (β‐APP) in the CC axonal fibers. Treatment of the CC slices with Glut resulted in β‐APP accumulation in the CC fibers as detected by Western blot, reflecting an impairment of axonal transport function. This injurious effect of Glut on CC axonal transport was significantly blocked by MK801. Taken together, these results show that NMDARs are expressed in the adult CC and are involved in excitotoxic activity in adult CC slices in vitro. © 2012 Wiley Periodicals, Inc.
Hyperexcitability of inferior colliculus neurons caused by acute noise exposure
Authors: Niu Yuguang , Kumaraguru Anand , Wang Rongguang , Sun Wei
Published: November 2012

Noise exposure is one of the most common causes of hearing loss. Recent studies found that noise exposure‐induced cochlear damage may change the excitability and tonotopic organization of the central auditory system (CAS). This plasticity was suspected to be related to tinnitus and hyperacusis. However, how cochlear damage affects CAS function and causes these neurologic diseases is still not clear. CAS function is activity dependent, so we hypothesize that a restricted cochlear lesion might disrupt the balance of excitation and inhibition in the CAS and thereby affect its neural activity. To test this hypothesis, we studied the effects of narrow‐band noise exposure on the firing properties of neurons in the inferior colliculus (IC), which has complex neural circuits and plays an important role in sound processing. We found that noise exposure (20 kHz, 105 dB SPL, 30 min) caused a dramatic decrease of the characteristic frequency in about two‐thirds of high‐frequency neurons with/without causing a significant threshold shift. The noise exposure also caused an increase in firing rate of the low‐frequency neurons at suprathreshold levels, whereas it dramatically decreased the firing rate of the high‐frequency neurons. Our results suggest that acute high‐frequency noise exposure may increase low‐frequency responsiveness by causing hyperexcitability of low‐frequency neurons. The functional change of the low‐frequency neurons may be related to the disruption of side‐band inhibition at the noise exposure frequencies caused by cochlear damage. © 2012 Wiley Periodicals, Inc.
Sensitive determination of polycyclic aromatic hydrocarbons in water samples by HPLC coupled with SPE based on graphene functionalized with triethoxysilane
Authors: Huang Ke‐Jing , Li Jing , Liu Yan‐Ming , Wang Lan
Published: November 2012

The graphene functionalized with (3‐aminopropyl) triethoxysilane was synthesized by a simple hydrothermal reaction and applied as SPE sorbents to extract trace polycyclic aromatic hydrocarbons (PAHs) from environmental water samples. These sorbents possess high adsorption capacity and extraction efficiency due to strong adsorption ability of carbon materials and large specific surface area of nanoparticles, and only 10 mg of sorbents are required to extract PAHs from 100 mL water samples. Several condition parameters, such as eluent and its volume, adsorbent amount, sample volume, sample pH, and sample flow rate, were optimized to achieve good sensitivity and precision. Under the optimized extraction conditions, the method showed good linearity in the range of 1–100 μg/L, repeatability of the extraction (the RSDs were between 1.8 and 2.9%, n = 6), and satisfactory detection limits of 0.029–0.1 μg/L. The recoveries of PAHs spiked in environmental water samples ranged from 84.6 to 109.5%. All these results demonstrated that this new SPE technique was a viable alternative to conventional enrichment techniques for the extraction and analysis of PAHs in complex samples.
Determination of phenolic acids in plant extracts using CZE with on‐line transient isotachophoretic preconcentration
Authors: Honegr Jan , Pospíšilová Marie
Published: November 2012

A novel transient ITP–CZE for preconcentration and determination of seven phenolic acids (caffeic acid, cinnamic acid, p‐coumaric acid, ferulic acid, protocatechuic acid, syringic acid, and vanilic acid) was developed and validated. Effects of several factors such as control of EOF, pH and buffer concentration, addition of organic solvents and CDs, and conditions for sample injection were investigated. Sample self‐stacking was applied by means of induction of transient ITP, which was realized by adding sodium chloride into the sample. The CZE was realized in 200 mM borate buffer (
9.2) containing 37.5% methanol, 0.001% hexadimethrine bromide, and 15 mM 2‐hydroxypropyl‐β‐CD. Under the optimal conditions for analysis, analytes were separated within 20 min. Linearity was tested for each compound in the concentration range of 0.1–10 μg/mL (R = 0.9906–0.9968) and the detection limits (S/N = 3) ranged from 11 ng/mL (protocatechuic acid) to 31 μg/mL (syringic acid). The validated method was applied to the ethanolic extract of Epilobium parviflorum, Onagraceae. The method of SPE was used for the precleaning of the sample.
Screening active anti‐breast cancer compounds from Cortex Magnolia officinalis by 2DLC–MS
Authors: Hou Xiaofang , Yuan Xilong , Zhang Bing , Wang Sicen , Chen Qinhua
Published: November 2012

Most of the anti‐breast cancer drugs are often limited owing to drug resistance and serious adverse reactions. Therefore, development of more targeted and low toxic drugs from traditional Chinese medicines for breast cancer are needed. At the same time, establishment of fast and effective drug screening methods are urgently required. We describe here a 2D LC method of MDA‐MB‐231 cell membrane chromatography combined with HPLC/MS for recognition, separation, and identification of target components from traditional Chinese medicine Cortex Magnolia officinalis. The MDA‐MB‐231 cells membrane was used to prepare the chromatographic stationary phase in the first dimension. The active compounds had a retention characteristic on the cell membrane chromatography model (10 × 2.0 mm, 5 μm). The retention fractions were enriched using an online C18 column (10 × 1.0 mm, 5 μm) and were analyzed by the second dimension RP chromatography. Finally, the activity of the retention fractions was tested through in vitro experiments. Results showed that the retention fractions were honokiol and magnolol and the inhibition rate on MDA‐MB‐231 cell growth were 23 and 64 μM, respectively. These results support the conclusion that this coupled analytical technique could be an efficient method in drug discovery.
On Price Competition with Market Share Delegation Contracts
Authors: Kopel Michael , Lambertini Luca
Published: November 2012

We identify a mistake in the specification of the demand system used in the strategic delegation model based on market shares by Jansen, van Lier and van Witteloostuijn, whereby the price remains above marginal cost when goods are homogeneous. After amending this aspect, we perform a profit comparison with the alternative delegation scheme à la Fershtman and Judd (1987). Copyright © 2012 John Wiley & Sons, Ltd.
Optical inhibition of motor nerve and muscle activity in vivo
Authors: Liske Holly , Towne Chris , Anikeeva Polina , Zhao Shengli , Feng Guoping , Deisseroth Karl , Delp Scott
Published: November 2012

Introduction: There is no therapeutic approach that provides precise and rapidly reversible inhibition of motor nerve and muscle activity for treatment of spastic hypertonia. Methods: We used optogenetics to demonstrate precise and rapidly reversible light‐mediated inhibition of motor nerve and muscle activity in vivo in transgenic Thy1::eNpHR2.0 mice. Results: We found optical inhibition of motor nerve and muscle activity to be effective at all muscle force amplitudes and determined that muscle activity can be modulated by changing light pulse duration and light power density. Conclusions: This demonstration of optical inhibition of motor nerves is an important advancement toward novel optogenetics‐based therapies for spastic hypertonia. Muscle Nerve 47: 916–921, 2013
Botulinum toxin modulates cortical maladaptation in post‐stroke spasticity
Authors: Huynh William , Krishnan Arun V. , Lin Cindy S.‐Y. , Vucic Steve , Katrak Pesi , Hornberger Michael , Kiernan Matthew C.
Published: November 2012

Introduction: Maladaptive plasticity involving the unaffected hemisphere (UH) in stroke patients may contribute to post‐stroke deficits, including spasticity. We investigated the central and peripheral effects of botulinum toxin in post‐stroke spasticity to determine whether there is modulation of cortical processes in the UH. Methods: Transcranial magnetic stimulation and peripheral nerve excitability studies were undertaken in 5 stroke patients with upper limb spasticity before (T1) and 6 weeks after (T2) botulinum injection. Results: Transcranial magnetic stimulation demonstrated inexcitable motor cortices of the affected hemisphere at T1 and T2, and short‐interval intracortical inhibition (SICI) in the UH was significantly reduced at T1. At T2, SICI in the UH increased significantly compared with T1, normalizing to controls, and was found to be associated with clinical improvements in spasticity. Peripheral excitability parameters were unchanged after injection. Conclusion: Cortical excitability changes were demonstrated in UH, suggesting that the clinical benefits of botulinum toxin relate to modulation of abnormal central reorganization (maladaptive plasticity) in post‐stroke spasticity. Muscle Nerve, 2013