bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement of Stability and Anticancer Activity of Chlorambucil‐Tetrapeptide Conjugate Vesicles
Authors: Zhang Wei , Zhu Wenjun , He Ruiyu , Fang Shuo , Zhang Yemin , Yao Chen , Ismail Muhammad , Li Xinsong
Published: March 2016

Chlorambucil is a classic nitrogen mustard drug that has been used in the treatment of cancers. It may induce neutropenia, thrombocytopenia and other side effects because of its short lifetime and off‐target effect. In this report, chlorambucil‐tetrapeptide (AAAK, A3K) conjugate vesicles were developed to improve the stability and bioactivity of chlorambucil. First of all, chlorambucil‐A3K conjugate was synthesized by solid phase synthesis strategy. Secondly, the chlorambucil‐A3K conjugate was assembled and characterized by critical aggregation concentration, circular dichroism, dynamic light scattering and transmission electron microscopy. The results indicated that the chlorambucil‐A3K conjugate can be assembled to form spherical vesicles with an average diameter of 390.5 nm, and high drug loading about 47.1% is reached. Surprisingly, the preliminary biological evaluation of the chlorambucil‐A3K conjugate vesicles revealed the best in vitro anticancer activity against HeLa, HepG‐2 and MCF‐7 cell lines compared with chlorambucil and chlorambucil‐A3K conjugate free drugs. Furthermore, conjugate vesicles showed excellent in vivo antitumoral activity. It can be partly attributed to their vesicular structure which isolates chlorambucil active moiety from aqueous solution to retard degradation before killing cancer cells. Therefore, chlorambucil‐peptide (A3K) conjugate vesicles may be an alternative delivery system of chlorambucil.
Disarming an Electrophilic Warhead: Retaining Potency in Tyrosine Kinase Inhibitor (TKI)‐Resistant CML Lines While Circumventing Pharmacokinetic Liabilities
Authors: Ali Ahmed M. , Gómez‐Biagi Rodolfo F. , Rosa David A. , Lai Ping‐Shan , Heaton William L. , Park Ji Sung , Eiring Anna M. , Vellore Nadeem A. , de Araujo Elvin D. , Ball Dan P. , Shouksmith Andrew E. , Patel Ami B. , Deininger Michael W. , O'Hare Thomas , Gunning Patrick T.
Published: March 2016

Pharmacologic blockade of the activation of signal transducer and activator of transcription 3 (STAT3) in tyrosine kinase inhibitor (TKI)‐resistant chronic myeloid leukemia (CML) cell lines characterized by kinase‐independent resistance was shown to re‐sensitize CML cells to TKI therapy, suggesting that STAT3 inhibitors in combination with TKIs are an effective combinatorial therapeutic for the treatment of CML. Benzoic acid‐ and hydroxamic acid‐based STAT3 inhibitors SH‐4‐054 and SH‐5‐007, developed previously in our laboratory, demonstrated promising activity against these resistant CML cell lines. However, pharmacokinetic studies in murine models (CD‐1 mice) revealed that both SH‐4‐054 and SH‐5‐007 are susceptible to glutathione conjugation at the para position of the pentafluorophenyl group via nucleophilic aromatic substitution (SNAr). To determine whether the electrophilicity of the pentafluorophenyl sulfonamide could be tempered, an in‐depth structure–activity relationship (SAR) study of the SH‐4‐054 scaffold was conducted. These studies revealed that AM‐1‐124, possessing a 2,3,5,6‐tetrafluorophenylsulfonamide group, retained STAT3 protein affinity (Ki=15 μm), as well as selectivity over STAT1 (Ki>250 μm). Moreover, in both hepatocytes and in in vivo pharmacokinetic studies (CD‐1 mice), AM‐1‐124 was found to be dramatically more stable than SH‐4‐054 (t1/2=1.42 h cf. 10 min, respectively). AM‐1‐124 is a promising STAT3‐targeting inhibitor with demonstrated bioavailability, suitable for evaluation in preclinical cancer models.
Evaluation of EuII‐based positive contrast enhancement after intravenous, intraperitoneal, and subcutaneous injections
Authors: Ekanger Levi A. , Polin Lisa A. , Shen Yimin , Haacke E. Mark , Allen Matthew J.
Published: March 2016

EuII‐based contrast agents offer physiologically relevant, metal‐based redox sensing that is unachievable with GdIII‐based contrast agents. To evaluate the in vivo contrast enhancement of EuII as a function of injection type, we performed intravenous, intraperitoneal, and subcutaneous injections in mice. Our data reveal a correlation between reported oxygen content and expected rates of diffusion with the persistence of EuII‐based contrast enhancement. Biodistribution studies revealed europium clearance through the liver and kidneys for intravenous and intraperitoneal injections, but no contrast enhancement was observed in organs associated with clearance. These data represent a step toward understanding the behavior of EuII‐based complexes in vivo. Copyright © 2016 John Wiley & Sons, Ltd.
The Role of Size and Dimerization of Decorating Plasmonic Silver Nanoparticles on the Photoelectrochemical Solar Water Splitting Performance of BiVO4 Photoanodes
Authors: Valenti Marco , Kontoleta Evgenia , Digdaya Ibadillah A. , Jonsson Magnus P. , Biskos George , Schmidt‐Ott Andreas , Smith Wilson A.
Published: March 2016

Ag nanoparticles (NPs) are deposited on BiVO4 photoanodes to study their effect on the photoelectrochemical (PEC) water splitting performance of the semiconductor. 15 nm light‐absorbing NPs and 65 nm light scattering NPs were studied separately to compare their light trapping ability for enhancing the semiconductor's absorption through light concentration and light scattering, respectively. The 15 nm NPs enhanced the BiVO4 external quantum efficiency throughout the semiconductor's absorption range (e.g., ≈2.5 fold at λ=400 nm). However, when a hole scavenger was added to the electrolyte, no enhancement was observed upon NP deposition, indicating that the NPs only facilitate the injection of holes from the semiconductor surface to the electrolyte but do not enhance its absorption. On the other hand, the 65 nm scattering NPs not only facilitated hole injection to the electrolyte, but also enhanced the absorption of the semiconductor (by ≈6 %) through light scattering. Such a dual effect, i.e., of enhancing both the surface properties and the absorption of the semiconductor, makes light scattering Ag NPs an ideal decoration for PEC water splitting photoelectrodes.
Translational Dynamics of Lipidated Ras Proteins in the Presence of Crowding Agents and Compatible Osmolytes
Authors: Patra Satyajit , Erwin Nelli , Winter Roland
Published: March 2016

Ras proteins are small GTPases and are involved in transmitting signals that control cell growth, differentiation, and proliferation. Since the cell cytoplasm is crowded with different macromolecules, understanding the translational dynamics of Ras proteins in crowded environments is crucial to yielding deeper insight into their reactivity and function. Herein, the translational dynamics of lipidated N‐Ras and K‐Ras4B is studied in the bulk and in the presence of a macromolecular crowder (Ficoll) and the compatible osmolyte and microcrowder sucrose by fluorescence correlation spectroscopy. The results reveal that N‐Ras forms dimers due to the presence of its lipid moiety in the hypervariable region, whereas K‐Ras4B remains in its monomeric form in the bulk. Addition of a macromolecular crowding agent gradually favors clustering of the Ras proteins. In 20 wt % Ficoll N‐Ras forms trimers and K‐Ras4B dimers. Concentrations of sucrose up to 10 wt % foster formation of N‐Ras trimers and K‐Ras dimers as well. The results can be rationalized in terms of the excluded‐volume effect, which enhances the association of the proteins, and, for the higher concentrations, by limited‐hydration conditions. The results of this study shed new light on the association state of these proteins in a crowded environment. This is of particular interest for the Ras proteins, because their solution state—monomeric or clustered—influences their membrane‐partitioning behavior and their interplay with cytosolic interaction partners.
Evaluating Battery‐like Reactions to Harvest Energy from Salinity Differences using Ammonium Bicarbonate Salt Solutions
Authors: Kim Taeyoung , Rahimi Mohammad , Logan Bruce E. , Gorski Christopher A.
Published: March 2016

Mixing entropy batteries (MEBs) are a new approach to generate electricity from salinity differences between two aqueous solutions. To date, MEBs have only been prepared from solutions containing chloride salts, owing to their relevance in natural salinity gradients created from seawater and freshwater. We hypothesized that MEBs could capture energy using ammonium bicarbonate (AmB), a thermolytic salt that can be used to convert waste heat into salinity gradients. We examined six battery electrode materials. Several of the electrodes were unstable in AmB solutions or failed to produce expected voltages. Of the electrode materials tested, a cell containing a manganese oxide electrode and a metallic lead electrode produced the highest power density (6.3 mW m−2). However, this power density is still low relative to previously reported NaCl‐based MEBs and heat recovery systems. This proof‐of‐concept study demonstrated that MEBs could indeed be used to generate electricity from AmB salinity gradients.
Iron deficiency and risk of early readmission following a hospitalization for acute heart failure
Authors: Núñez Julio , Comín‐Colet Josep , Miñana Gema , Núñez Eduardo , Santas Enrique , Mollar Anna , Valero Ernesto , García‐Blas Sergio , Cardells Ingrid , Bodí Vicent , Chorro Francisco J. , Sanchis Juan
Published: March 2016

Aims

Early rehospitalization after an episode of acute heart failure (AHF) remains excessively high and its prediction a contemporary challenge. Iron deficiency (ID) is a frequent finding in AHF, but its prognostic implications remain unclear. We sought to evaluate the association between ID and risk of 30‐day readmission in an unselected cohort of patients discharged for AHF.

Methods and results

Serum ferritin and transferrin saturation (TSAT) were measured before discharge in 626 consecutive patients with AHF in a single teaching centre. ID was defined as serum ferritin <100 µg/L (absolute ID) or ferritin 100–299 µg/L with a TSAT <20% (functional ID). Cox regression adapted for competing events was used to determine the association between ID and the risk of 30‐day readmissions. Mean age was 73.4 ± 10.4 years, 48% were females, and 52.1% showed an LVEF >50%. ID was identified in 463 patients (74%): 302 (48.2%) as absolute ID and 161 (25.7%) as functional ID. At 30‐day post‐discharge, 20 (3.2%) patients died and 103 (16.5%) were readmitted. Patients with absolute ID showed an increased rate of readmission compared with those with functional ID and no ID (19.9, 13, and 13.5%, respectively, P = 0.005). In a multivariate setting, absolute ID remained associated with higher risk of readmission [hazard ratio (HR) 1.72; 95% confidence interval (CI) 1.13–2.60, P = 0.011]. Compared with patients without ID, functional ID was not related to the risk of readmission (HR 0.87; 95% CI 0.46–1.62, P = 0.652).

Conclusion

In patients with AHF, absolute ID, but not functional ID, was associated with an increased risk of early readmission.
2,2,2‐Trifluoroethyl Oxalates in the One‐Pot Parallel Synthesis of Hindered Aliphatic Oxamides
Authors: Bogolubsky Andrey V. , Moroz Yurii S. , Mykhailiuk Pavel K. , Pipko Sergey E. , Grishchenko Alexander V. , Zhemera Anton V. , Konovets Anzhelika I. , Doroschuk Roman A. , Dmytriv Yurii V. , Zaporozhets Olga A. , Tolmachev Andrey
Published: March 2016

A simple parallel synthesis approach to unsymmetrical N1,N2‐substituted aliphatic oxamides using methyl (2,2,2‐trifluoroethyl) oxalate and bis(2,2,2‐trifluoroethyl) oxalate was developed. The method was validated on a 52‐membered set of the oxamides, derived mainly from hindered primary and secondary aliphatic amines, and gave the products with a high overall success rate in moderate yields.
Silatrane as a Practical and Selective Reagent for the Reduction of Aryl Aldehydes to Benzylic Alcohols
Authors: Skrypai Vladislav , Hurley Joseph J. M. , Adler Marc J.
Published: March 2016

Hydrosilanes are cheap, readily available substrates, yet they do not see as extensive use for simple carbonyl reductions as borohydrides. Hydrosilane reducing agents broadly fall into one of two general categories: either a) they are easy to handle and require expensive and/or hazardous additives, or b) they are difficult and/or dangerous to handle. This work details the discovery of mild and functional group compatible conditions utilizing hydrosilatrane for the selective reduction of aryl aldehydes to benzylic alcohols without unwanted formation of ethers or deoxygenated products. This method offers significant advances in silane reductions as silatrane is an air‐ and moisture‐stable yet relatively reactive reducing agent that can be used in benchtop open air reactions.
Organocatalytic Enantioselective Synthesis of P‐Stereogenic Chiral Oxazaphospholidines
Authors: Wang Lanlan , Du Zhijun , Wu Qiang , Jin Rizhe , Bian Zheng , Kang Chuanqing , Guo Haiquan , Ma Xiaoye , Gao Lianxun
Published: March 2016

The enantioselective synthesis of P‐stereogenic chiral organophosphines under organocatalysis is a challenging research field, and reports that use this approach are rare. Herein, we have developed the enantioselective synthesis of P‐stereogenic chiral oxazaphospholidines by using a bicyclic thiazole as the organocatalyst in the P–N and P–O bond‐forming reaction. The P‐chiral products were prepared in high yields with moderate enantioselectivities. The base that was used in this process had a significant influence on the enantioselectivity of the reaction and in some cases led to the opposite configuration of the P‐chiral center.
Solid‐Phase Synthesis of Hybrid Urea Oligomers Containing Conservative Thiourea Mutations
Authors: Antunes Stéphanie , Douat Céline , Guichard Gilles
Published: March 2016

The introduction of a thiourea unit at a selected position in the backbone of aliphatic N,N′‐linked urea foldamers can be used to locally modulate the secondary structure and physicochemical properties. To facilitate scanning the effect of thiourea introduction into biologically active oligourea helices, we have investigated the solid‐phase synthesis of oligoureas containing a single oxo‐to‐thioxo replacement in their sequence. Several suitably protected activated monomers were considered, and conditions for their coupling and deprotection were evaluated and compared. The synthesis of oligo(thio)ureas on TFA‐labile resins (i.e., Rink amide resin; TFA = trifluoroacetic acid) required careful optimization, and the choice of N‐Fmoc‐aminoalkyl isothiocyanates (Fmoc = fluorenylmethoxycarbonyl) as monomers for thiourea‐bond formation was found to be critical.
Enhanced c‐Fos expression in the central amygdala correlates with increased thigmotaxis in rats with peripheral nerve injury
Authors: Morland R.H. , Novejarque A. , Spicer C. , Pheby T. , Rice A.S.C.
Published: March 2016

Background

Pain is associated with affective, cognitive and sensory dysfunction. Animal models can be used to observe ethologically relevant behaviours such as thigmotaxis, giving insight into how ongoing sensory abnormalities influence natural rodent behaviours. The amygdala is a complex group of nuclei implicated in the integration and generation of emotional behavioural responses, including those associated with pain, and a region known as the central amygdala is particularly associated with generation of behavioural responses, due to its links to the descending pain modulation pathways; as such, study of amygdalar c‐Fos immunoreactivity can help identify the neuronal circuits involved.

Method

This study investigated changes in both nociceptive evoked responses and open field behaviour following spinal nerve transection (SNT) in male Wistar rats, and attempted to correlate these with changes in central amygdala c‐Fos immunoreactivity.

Results

Fourteen days after SNT, mechanical hypersensitivity was present in the hind paw ipsilateral to site of injury. Thigmotactic behaviour was significantly increased in both SNT and sham surgery animals, with c‐Fos immunoreactivity in the central amygdala significantly greater in SNT animals compared to both sham and naive groups. Activation was greatest in the capsular and lateral subnuclei of the central amygdala, and in the caudal‐most regions. There was a strong correlation between thigmotactic behaviour and central amygdala activation following SNT surgery not seen in sham animals suggesting a role for the amygdala in behavioural responses to peripheral nerve injury.

Conclusions

This study provides evidence to support the role of the amygdala in thigmotactic open field behaviour following SNT.

What does this study add?

Thigmotaxis and amygdala activation are positively correlated in rats following spinal nerve transection.

Behavioural changes seen in sham animals did not correlate with amygdala activation, suggesting amygdala activation is related to nociceptive input.

Evoked measures, such as hindpaw withdrawal, are not correlated with either thigmotaxis or amygdala activation, emphasizing the importance of complex behaviours when studying pain.
A randomized phase I trial evaluating the effects of inhaled 50–50% N2O–O2 on remifentanil‐induced hyperalgesia and allodynia in human volunteers
Authors: Wehrfritz A. , Schaefer S. , Troester A. , Noel N. , Bessiere B. , Apiou‐Sbirlea G. , Simonnet G. , Schuettler J. , Richebé P.
Published: March 2016

Background

Opioids are known to relieve pain, and also aggravate pre‐existing hyperalgesia. In animal studies, the N‐methyl‐d‐aspartate‐receptor antagonist nitrous oxide (N2O) was able to prevent hyperalgesia. The present study evaluated the effect of N2O on hyperalgesia after remifentanil infusion in healthy volunteers.

Methods

Twenty‐one healthy volunteers were enrolled in this placebo‐controlled cross‐over study. Transcutaneous electrical stimulation at high current densities induced spontaneous acute pain and stable areas of hyperalgesia. Each volunteer underwent the following four sessions: (1) 50–50% N2–O2 and i.v. saline; (2) 50–50% N2–O2 and i.v. remifentanil 0.1 μg/kg/min; (3) 50–50% N2O–O2 and i.v. saline; (4) 50–50% N2O–O2 and i.v. remifentanil 0.1 μg/kg/min. Inhaled gas mixtures lasted for 60 min, i.v. drug administration for 30 min. Visual analogue scale pain intensity, areas of pinprick hyperalgesia and touch‐evoked allodynia were assessed repeatedly for 160 min.

Results

Data of 19 volunteers were analysed. There were significant time and treatment effects regarding areas of hyperalgesia and allodynia (p < 0.02). The area of hyperalgesia was significantly reduced in the N2O + remifentanil session compared to the remifentanil session (35.88 ± 22.37 vs. 43.55 ± 18.48 cm2, p = 0.004). The area of allodynia was significantly reduced in the N2O + remifentanil session compared to the remifentanil session (29.95 ± 16.15 vs. 34.80 ± 15.35 cm2, p = 0.008). The pain intensity was significantly reduced in the N2O + remifentanil session compared to the remifentanil session (37.96 ± 12.78 vs. 42.15 ± 13.34 mm, p < 0.0001).

Conclusions

Nitrous oxide significantly reduced hyperalgesia, allodynia and pain intensity aggravated after remifentanil administration in a human volunteer model.

What does this study add?

This study brings the evidence that N2O reduces the remifentanil aggravated secondary hyperalgesia in human volunteers exposed to a well‐known model of electrical pain. N2O was able to oppose the hyperalgesia, the allodynia and the pain intensity consecutive to remifentanil use in this specific pain model.
Technique for reliable sentinel node biopsy in squamous cell carcinomas of the floor of mouth
Authors: Stoeckli Sandro J. , Huebner Thomas , Huber Gerhard F. , Broglie Martina A.
Published: March 2016

Background

Applicability of sentinel node biopsy (SNB) for tumors of the floor of mouth (FOM) is controversial.

Methods

Prospective evaluation of the accuracy of gamma‐probe‐guided superselective neck dissection of the preglandular triangle of level I for SNB in FOM squamous cell carcinoma (SCC) after preoperative lymphoscintigraphy and single photon emission CT (SPECT)/CT.

Results

In total, 22 sentinel lymph nodes were harvested in level I. Eight of 22 (36%) were seen on lymphoscintigraphy and 11 (50%) on SPECT/CT. Eleven sentinel lymph nodes (50%) were only detected intraoperatively. In unilateral tumors, 20% were contralateral, and, in midline tumors, 93% showed bilateral level I sentinel lymph nodes. The false‐negative rate was 8.3%, the negative predictive value was 96.4%, and the false‐omission rate was 3.6%. The ultimate neck control rate, including salvage treatment, was 100%.

Conclusion

SNB in FOM can be reliably performed using the presented surgical technique. Level I exploration, bilaterally in midline tumors, is mandatory irrespective of the visualization of sentinel lymph nodes in other levels. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1367–1372, 2016
Density Functional Study of the Reaction Mechanism of Two Oxiimine Alcohol Formations and Their Novel Rearrangements
Authors: Kaya Yunus
Published: March 2016

In this study, the reaction mechanisms of isonitrosoacetophenone (inapH) with ethanolamine (ea) and 1‐phenylethanolamine (pea) have been investigated theoretically using B3LYP/6‐311G(d,p) method to explain why the formation and unexpected rearrangement products occur or not occur. While the reaction between isonitrosoacetophenone (inapH) with ethanolamine gives oximine alcohol (Ib), the reaction of 1‐phenylethanolamine with inapH results in the formation of oximine alcohol with a different substituent (Ia) and amido alcohol (IIa), which is the unexpected rearrangement product. The rearrangement driving forces of compounds from Ia to IIa are calculated as ca. 28 and 23 kJ/mol in the gas and EtOH phases, respectively. These driving forces have been calculated ca. 46 and 45 kJ/mol for the rearrangement of compound Ib to obtain IIb in the same phases, respectively. This high driving force shows that the compound IIb cannot be obtained from rearrangement of compound Ib as described experimentally in the literature. In addition, as the DFT functionals poorly describe dispersion effects, dispersion correction for reaction heat and free‐energy barrier was estimated using the wB97X‐D/6‐311G(d,p). In general, the relative free energies of all molecules calculated from wB97XD method are lower than performed from B3LYP level. The changes of thermodynamic properties for all molecules with temperature ranging from 100 to 500 K have been obtained using the statistical thermodynamic method.
Using periodic hydrologic and geochemical sampling with limited continuous monitoring to characterize remote karst aquifers in the Kaweah River Basin, California, USA
Authors: Tobin Benjamin W. , Schwartz Benjamin F.
Published: March 2016

Hydrogeologic field work in remote settings is often challenging: assessing spring behaviour and aquifer characteristics can be expensive in both time commitment and resources needed to assess these systems. In this study, we document the hydrology and geochemistry of 47 perennial karst springs in the Kaweah River, a mountain river basin in the Sierra Nevada, California. After preliminary hydrogeochemical characterization and grouping, selected springs were continuously monitored to further assess aquifer characteristics in each group. Later, in areas without previous dye‐tracing work, traces were conducted to establish connections between large sinking streams and springs.

The springs have a wide range of inter‐spring and intra‐spring variability in discharge and geochemistry. We assessed this variability by performing statistical comparisons with spring chemistry and principal components analysis of all measured variables. Results show that springs can be divided into two distinct groups: high elevation springs of the Mineral King Valley and lower elevation springs throughout the rest of the basin. Continuous discharge, temperature and specific conductivity data from four springs (two from each group) were then used to characterize the hydrograph recession behaviour of springs in each group. Both groups showed statistically similar baseflow recession slopes, suggesting that both groups contain baseflow storage compartments with similar hydrogeologic properties. The biggest difference between each group is the variability in amount of water remaining in the aquifer during baseflow conditions. High elevation springs have lower baseflow discharges, relative to peak flow, than lower elevation springs, despite the fact that more precipitation falls at higher elevation. This is likely caused by differences in the amount of soil and epikarst storage, which are related to recent geomorphic events: high elevation aquifers were glaciated as recent as 41 thousand years ago (kya), while there is no evidence that low elevation aquifers were glaciated. As a result, lower elevations have developed thicker soils, weathered bedrock and epikarst. Copyright © 2016 John Wiley & Sons, Ltd.
Dihydroartemisinin restricts hepatic stellate cell contraction via an FXR‐S1PR2‐dependent mechanism
Authors: Xu Wenxuan , Lu Chunfeng , Zhang Feng , Shao Jiangjuan , Zheng Shizhong
Published: March 2016

Hepatic stellate cells (HSCs) are universally acknowledged to play a stimulative role in the pathogenesis of hepatic fibrosis and portal hypertension. HSCs when activated in response to liver injury are characterized with many changes, with HSC contraction being the most common cause of portal hypertension. Previous studies have shown that dihydroartemisinine (DHA) is a potential antifibrotic natural product by inducing HSC apoptosis, whereas the role of DHA in regulating HSC contraction and the mechanisms involved remain a riddle. Recent studies have emphasized on the importance of farnesoid X receptor (FXR) and sphingosine‐1‐phosphate receptor 2 (S1PR2) in controlling cell contractility. This study showed that DHA strongly induced the mRNA and protein expression of FXR in LX‐2 cells in a dose‐ and time‐dependent manner and inhibited HSC activation, implying a conceivable impact of DHA on HSC contraction. The gel contraction assays and fluorescence staining of actin cytoskeleton verified that DHA dose‐dependently limited contraction of collagen lattices and reorganization of actin stress fibers in LX‐2 cells. DHA also decreased the phosphorylation of myosin light chain that is responsible for the contractile force of HSCs. Furthermore, gain‐ or loss‐of‐function analyses exhibited a FXR‐ and S1PR2‐dependent mechanism of inhibiting HSC contraction by DHA, and DHA decreased S1PR2 expression by modulating FXR activation. Subsequent work revealed that inhibition of both Ca2+‐dependent and Ca2+‐sensitization signaling transductions contributed to DHA‐induced HSC relaxation. In summary, these findings suggest that DHA could restrict HSC contraction through modulating FXR/S1PR2 pathway‐mediated Ca2+‐dependent and Ca2+‐sensitization signaling. Our discoveries make DHA a potential candidate for portal hypertension. © 2016 IUBMB Life 68(5):376–387, 2016
Where have all the inosines gone? Conflicting evidence for A‐to‐I editing of the anticodon of higher eukaryotic questions the dogma of a universal wobble‐mediated decoding of CGN codons
Authors: Igloi Gabor L. , Aldinger Carolin A.
Published: March 2016

Codon–anticodon recognition between triplets of an mRNA and a specific tRNA is the key element in the translation of the genetic code. In general, the precision of this process is dominated by a strict Watson‐Crick base‐pairing scheme. However, the degeneracy of the genetic code led Crick to propose the Wobble Hypothesis, permitting a less restraining interaction with the third base of the codon and involving the participation of inosine for decoding C‐ending codons. The concept that the anticodon base A34 of
in all eukaryotes, eubacteria, and plant chloroplasts is converted to I34 is firmly anchored in the literature despite conflicting evidence for its existence in higher eukaryote cytoplasmic
. Here, we provide additional data and summarize the arguments favoring and contradicting post‐transcriptional deamination of this position. A hypothesis that resolves the apparent conflict is proposed. © 2016 IUBMB Life, 68(6):419–422, 2016
Modeling and Forecasting Large Realized Covariance Matrices and Portfolio Choice
Authors: Callot Laurent A. F. , Kock Anders B. , Medeiros Marcelo C.
Published: March 2016

We consider modeling and forecasting large realized covariance matrices by penalized vector autoregressive models. We consider Lasso‐type estimators to reduce the dimensionality and provide strong theoretical guarantees on the forecast capability of our procedure. We show that we can forecast realized covariance matrices almost as precisely as if we had known the true driving dynamics of these in advance. We next investigate the sources of these driving dynamics as well as the performance of the proposed models for forecasting the realized covariance matrices of the 30 Dow Jones stocks. We find that the dynamics are not stable as the data are aggregated from the daily to lower frequencies. Furthermore, we are able beat our benchmark by a wide margin. Finally, we investigate the economic value of our forecasts in a portfolio selection exercise and find that in certain cases an investor is willing to pay a considerable amount in order get access to our forecasts. Copyright © 2016 John Wiley & Sons, Ltd.
Advantages of contrast‐enhanced ultrasonography over computed tomography for the detection of persistent type II endoleak after embolization: A case report
Authors: Cury Maysa Heineck , Cury Marcus Vinícius Martins , Godoy Marcos Roberto , Matielo Marcelo Fernando
Published: March 2016

The aim of this case report is to describe the use of contrast‐enhanced ultrasonography in the detection of a type II endoleak after prior embolization with Onyx. A 74‐year‐old male patient with hypertension previously underwent endovascular repair of a 7.1‐cm infrarenal aortic aneurysm. CT angiography surveillance revealed a type II endoleak associated with aneurysm sac expansion. Selective transarterial embolization of the endoleak was performed, but it was not possible to detect the persistent endoleak using CT angiography because of image artifacts caused by Onyx. Contrast‐enhanced ultrasonography enabled us to detect the persistent endoleak in this patient. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:522–526, 2016
Oxidation–reduction potential and lipid oxidation in ready‐to‐eat blue mussels in red sauce: criteria for package design
Authors: Bhunia Kanishka , Ovissipour Mahmoudreza , Rasco Barbara , Tang Juming , Sablani Shyam S
Published: March 2016

BACKGROUND

Ready‐to‐eat in‐package pasteurized blue mussels in red sauce requires refrigerated storage or in combination with an aerobic environment to prevent the growth of anaerobes. A low barrier packaging may create an aerobic environment; however, it causes lipid oxidation in mussels. Thus, evaluation of the oxidation–reduction potential (Eh) (aerobic/anaerobic nature of food) and lipid oxidation is essential. Three packaging materials with oxygen transmission rate (OTR) of 62 (F‐62), 40 (F‐40) and 3 (F‐3) cm3 m−2 day−1 were selected for this study. Lipid oxidation was measured by color changes in thiobarbituric acid reactive substances (TBARS) at 532 nm (TBARS@532) and 450 nm (TBARS@450).

RESULTS

Significantly higher (P < 0.05) TBARS@532 was found in mussels packaged in higher OTR film. TBARS@450 in mussels packaged with F‐62 and F‐40 gradually increased during refrigerated storage (3.5 ± 0.5 °C), but remained constant after 20 days of storage for mussels packaged with F‐3. The Eh of pasteurized sauce was not significantly affected (P > 0.05) by OTR and remained negative (< −80 mV) during storage. Negative Eh values can support the growth of anaerobes such as Clostridium botulinum. The headspace oxygen concentration was reduced by about 50% from its initial value during pasteurization, and then further declined during storage. The headspace oxygen concentration was higher in trays packaged with higher OTR film.

CONCLUSION

Mussels packed with high OTR film showed higher lipid oxidation, indicating that high barrier film is required for packaging of mussels. Pasteurized mussels must be kept in refrigerated storage to prevent growth of anaerobic proteolytic C. botulinum spores under temperature abuse. © 2016 Society of Chemical Industry
Visualization investigation on flow field of journal bearing with partial texture surface
Authors: Lin Qiyin , Wei Zhengying , Ma Shengli , Zhang Yubin , Wang Ning
Published: March 2016

The effect of partial texture surface on flow field of journal bearing is investigated experimentally using a visualization apparatus, which was less reported before. The visualization results show that there is a speeding‐up phenomenon in the movement of lubricant when lubricant flows from smooth surface region to dimple surface region, and the rising ratio of lubricant speed increases with the rotational speed of journal shaft. Copyright © 2016 John Wiley & Sons, Ltd.
Liver transplantation in Australia and New Zealand
Authors: McCaughan Geoffrey W. , Munn Stephen R.
Published: March 2016

Liver transplantation (LT) in Australia and New Zealand began in 1985. Over this time until December 2014, LT took place in 3700 adults and 800 children. LT is regulated with 1 unit, supported by the government, per state or region. Currently approximately 270 transplants take place per year. Organ donation rates are moderate in Australia (17 per 1 million of population) but very low in New Zealand (11 per 1 million of population). All the units share organ donors for fulminant hepatic failure cases (status 1). Recipient listing criteria and organ allocation criteria are commonly agreed to via National and Trans‐Tasman agreements, which are published online. Current survival rates indicate approximately 94% 1‐year survival with median survival in adults of approximately 20 years, whereas 75% of children are alive at 20 years. All units collaborate in research projects via the Australia and New Zealand Liver Transplant Registry and have published highly cited articles particularly on the prevention of hepatitis B virus recurrence. Outcomes for indigenous populations have also been analyzed. In conclusion, LT in Australia and New Zealand is well developed with transparent processes related to criteria for listing and organ allocation together with publication of outcomes. Liver Transplantation 22 830–838 2016 AASLD.
Improving durability of reinforced concrete structures by recycling wet‐ground MSWI bottom ash
Authors: Carsana M. , Gastaldi M. , Lollini F. , Redaelli E. , Bertolini L.
Published: March 2016

Municipal solid waste incineration (MSWI) generates high amounts of bottom ash that, after grinding, could be used as mineral addition for concrete. Wet grinding of the bottom ash can prevent the risk of deleterious expansion due to hydrogen evolution, associated to the presence of metallic aluminium. The pozzolanic behavior of the bottom ash may improve concrete resistance to the penetration of aggressive species. Advantages of recycling wet‐ground MSWI bottom ashes may even be higher when self‐compacting concrete (SCC) is used, which requires large quantity of fine powders (usually more than 500 kg/m3) to prevent segregation of the fresh mix. This paper describes the results of a research aimed at investigating the use of wet‐ground MSWI bottom ashes as mineral additions for the production of self‐compacting concrete. Several types of mineral additions (MSWI bottom ash, coal fly ash, and ground limestone) were used in replacement of 15, 30, and 45% of Portland cement. The results showed that the MSWI ash, added to the mix as a fine slurry obtained by wet‐grinding, led to the production of SCC concrete with compressive strength and resistance to chloride and carbonation similar, or even better, than those of concrete with same amount of coal fly ash.
Electrochromic Performance of Nickel Oxide Thin Film: Synthesis via Electrodeposition Technique
Authors: Kondalkar Vijay V. , Patil Pallavi B. , Mane Rahul M. , Patil Pramod S. , Choudhury Sipra , Bhosal Popatrao N.
Published: March 2016

Nanocrystalline Nickel oxide (NiO) thin films were electrochemically deposited onto ITO substrate at room temperature. In order to examine the optical absorption, crystal structure and surface morphology of deposited NiO thin films were characterized by means of UV–vis spectrophotometer, X‐ray diffraction (XRD) and scanning electron microscopy (SEM). The electrochromic (EC) performance of NiO thin film was investigated by means of cyclic voltammetry (CV), chronoamperometry (CA) and chronocoulometry (CC). The switching response of NiO thin film is found to be 5.62 s for coloration (tc) and 4.31 sec for bleaching (tb) with excellent reversibility. The electrochromic study shows highly reversible and the stable nature of electrochemically deposited NiO thin films which provides a versatile and promising application towards the fabrication of smart windows.
Development in Air Permeability of Natural Rubber Tire Tube Compound by Adding Variable Dosage of Nanoclay
Authors: Vasudeo Rane Ajay , VK Abitha , VR Uday , Samarth Nikesh , Jadhav Sainath , Patil Shivendra , VR Amit , Narute Suresh
Published: March 2016

Any material consisting of two or more components with different properties and distinct boundaries between their components can be referred to as a composite material. There are two groups of composites the first group comprises composites that are known as “filled materials”, the main feature of these materials is the existence of some basic or matrix material whose properties are improved by filling it with some particles and second group composites involves so called “reinforced materials”. The basic components of these materials are long and thin fibres possessing high strength and stiffness. Filler (particulate or thin fibers) is a solid material capable of changing the physical and chemical properties of materials by surface interaction or its lack thereof and by its own physical characteristics. High stiffness means that material exhibits low deformation under loading. Stiffness is an important property but it should be necessarily high. Ability of structure to have controlled deformation can be also important. Nano engineered polymeric materials are of great interest, rapidly growing new class of materials alternative to conventional filled polymers or polymer blends. Conventional clay plays the role of a loading agent or diluent without property enhancement or reinforcement and hence we have used nanoclay which imparts significant mechanical reinforcement and improved air permeability property for natural rubber based tube compound. Natural rubber/nanoclay along with other additives were mixed in a laboratory mixer for specified time and temperature, by determining rheological and curing properties rubber compounds were molded in to standard dimension sheets using a compression mold and molding machine thereafter specimens were prepared and characterized for hardness, modulus (100%, 200%), tensile strength, tension set, air permeability test and surface morphology.
Early Ataxia and Subsequent Parkinsonism: PLA2G6 Mutations Cause a Continuum Rather Than Three Discrete Phenotypes
Authors: Erro Roberto , Balint Bettina , Kurian Manju A. , Brugger Florian , Picillo Marina , Barone Paolo , Bhatia Kailash P. , Pellecchia Maria Teresa
Published: March 2016

View Supplementary Video 1

PLA2G6‐associated neurodegeneration comprises a heterogeneous spectrum of age‐related phenotypes, with three forms classically recognized, including infantile neuroaxonal dystrophy (INAD) with onset in infancy, atypical neuroaxonal dystrophy (atypical NAD) with onset in childhood, and dystonia‐parkinsonism (PARK14) with onset in early adulthood. We describe 3 cases that challenge this view, discuss the related literature, and suggest that PLA2G6 mutations cause a phenotypic continuum rather than three discrete phenotypes, further ensuing clinical implications.
Delusional Infestation in Parkinson's Disease
Authors: Davis Jennie L. , Kurek Julie A. , Sethi Kapil D. , Morgan John C.
Published: March 2016

Delusional infestation (DI), a form of psychosis, has rarely been reported in patients with Parkinson disease (PD). The clinical presentation and successful treatment of DI is illustrated through 5 cases. Each patient developed DI during treatment for moderate to advanced Parkinson's disease, and only 2 had cognitive impairment. Two patients were on monotherapy: 1 on a dopamine agonist and the other on trihexyphenidyl. Three patients were receiving complex combination therapy with 2 to 5 different anti‐Parkinsonian medications at the onset of their delusion. Selective discontinuation or reduction of these medications was key to the resolution of DI in each patient. Although the medication adjustments differed, the changes resulted in the reduction of anticholinergic effects or extracellular striatal dopamine levels. This series emphasizes the clinical features and management strategies for this disruptive form of psychosis in patients with PD.
Atropinic (Anticholinergic) Burden in Parkinson's Disease
Authors: De Germay Sibylle , Montastruc Jean‐Louis , Rousseau Vanessa , Chebane Leila , Bondon‐Guitton Emmanuelle , Moulis Florence , Durrieu Genevieve , Bagheri Haleh , Rascol Olivier , Pariente Antoine , Bégaud Bernard , Montastruc François
Published: March 2016

Use of atropinic drugs remains controversial in Parkinson's disease (PD) because there is insufficient evidence about their efficacy and they can induce serious adverse drug reactions. Atropinic risk scales were developed to help to identify atropinic drugs in prescription forms and to evaluate their burden in clinical practice. In the present review, we discuss the few studies investigating atropinic burden in PD and present the results of our study indicating that atropinic drugs are still widely prescribed in PD (almost 3 of 5 prescriptions) with a clinically significant atropinic burden in around 1 of 6 PD patients. Drugs mainly responsible for high values of atropinic burden were those used for nonmotor symptoms. Clinically significant atropinic burdens were mainly induced by associations of several “low‐risk” drugs. Physicians must be aware that in addition to classical atropinic antiparkinsonian drugs, many others (psychotropics) can contribute to increased atropinic burden in PD patients. © 2016 International Parkinson and Movement Disorder Society
Isolation of lactobacillus reuteri from Peyer's patches and their effects on sIgA production and gut microbiota diversity
Authors: Wang Panpan , Li Ya , Xiao Hang , Shi Yonghui , Le Guo‐wei , Sun Jin
Published: March 2016

Scope

We previously reported that specific Lactobacillus reuteri colonized within mouse Peyer's patches (PP) effectively prevented high fat diet induced obesity and low‐grade chronic inflammation. We further investigated the role of PP Lactobacillus reuteri on sIgA production in rats in this study.

Methods and results

Lactobacilli were isolated from rat PP. All isolates were L. reuteri and belonged to three phenotypes according to amplified fragment length polymorphism analysis. Typical strains of two main clusters, PP1 and PP2, were used to treat control and vitamin A deficient (VAD) rats, respectively. The feeding of PP1 and PP2 affected sIgA and Lactobacillus diversity by strain‐specific manner. Free sIgA was significantly increased by PP1 (p = 0.069) and PP2 (p < 0.05) in the control rats but not in the VAD rats. Only PP1 significantly changed PP Lactobacillus diversity in the control rats (p < 0.05). However, PP2 specifically changed ileal Lactobacillus diversity in both control and VAD rats. Fecal sIgA was correlated with PP Lactobacillus diversity (R2 = 0.7958, p = 0.011).

Conclusion

Modulation of sIgA production by PP L. reuteri of rat is dependent on vitamin A and change of Lactobacillus diversity in PP.
Zinc delays the progression of obesity‐related glomerulopathy in mice via down‐regulating P38 MAPK‐mediated inflammation
Authors: Luo Manyu , Luo Ping , Zhang Zhiguo , Payne Kristen , Watson Sara , Wu Hao , Tan Yi , Ding Yushuang , Sun Weixia , Yin Xinmin , Zhang Xiang , Liu Gilbert , Wintergerst Kupper , Miao Lining , Cai Lu
Published: March 2016

Objective

Obesity, particularly child obesity, is one of the most common public health problems in the world and raises the risk of end‐stage renal disease. Zinc (Zn) is essential for multiple organs in terms of normal structure and function; however, effects of Zn deficiency or supplementation among young individuals with obesity have not been well studied.

Methods

Weaned mice were fed high‐fat diets (HFD) with varied contents of Zn (Zn deficient, adequate, and supplemented) for 3 or 6 months. This study examined associations between renal pathogenesis and dietary Zn levels, specifically assessing inflammatory pathways by utilizing P38 MAPK inhibitor SB203580.

Results

HFD feeding induced typical syndromes of obesity‐related renal disorders, which worsened by Zn marginal deficiency. The progression of obesity‐related renal disorders was delayed by Zn supplementation. HFD induced renal inflammation, reflected by increased P38 MAPK phosphorylation along with increases of inflammatory cytokines MCP‐1, IL‐1β, IL‐6, and TNF‐α. P38 MAPK inhibition prevented renal pathological changes in mice fed with HFD and HFD/Zn deficiency.

Conclusions

P38 MAPK mediated the renal inflammatory responses, which played a central role in the pathogenesis of HFD‐induced renal disorders. Zn could delay the progression of obesity‐related kidney disease by down‐regulating P38 MAPK‐mediated inflammation.
MicroRNA‐29b promotes the adipogenic differentiation of human adipose tissue‐derived stromal cells
Authors: Zhang Xi‐Mei , Wang Li‐Hong , Su Dong‐Ju , Zhu Dan , Li Qiu‐Ming , Chi Mei‐Hua
Published: March 2016

Objective

Obesity is primarily characterized by the accumulation of large amounts of fat in adipose tissue. Within the adipose tissue, adipocytes are derived from adipose tissue‐derived stromal cells (ADSCs) via a specialized cell lineage differentiation process, and ADSCs play a key role in the generation and metabolism of adipose tissue. This study investigated whether microRNAs (miRNAs) play a role in adipocyte differentiation.

Methods

Using luciferase reporter and ChIP assays, the relationship between miR‐29b, SP1, and TNF‐α was examined.

Results

During the normal adipogenic differentiation of ADSCs, up‐regulation of miR‐29b promoted adipogenesis by enhancing SP1‐mediated inhibition of TNF‐α.

Conclusions

This study investigated the regulatory role of miR‐29b during the adipogenic differentiation of ADSCs and found that miR‐29b is an effective positive regulator of adipogenesis.
Diblock copolymers of polystyrene‐b‐poly(1,3‐cyclohexadiene) exhibiting unique three‐phase microdomain morphologies
Authors: Misichronis Konstantinos , Chen Jihua , Kahk Jong K. , Imel Adam , Dadmun Mark , Hong Kunlun , Hadjichristidis Nikos , Mays Jimmy W. , Avgeropoulos Apostolos
Published: March 2016

The synthesis and molecular characterization of a series of conformationally asymmetric polystyrene‐block‐poly(1,3‐cyclohexadiene) (PS‐b‐PCHD) diblock copolymers (PCHD: ∼90% 1,4 and ∼10% 1,2), by sequential anionic copolymerization high vacuum techniques, is reported. A wide range of volume fractions (0.27 ≤ ϕPS ≤ 0.91) was studied by transmission electron microscopy and small‐angle X‐ray scattering in order to explore in detail the microphase separation behavior of these flexible/semiflexible diblock copolymers. Unusual morphologies, consisting of PCHD core(PCHD‐1,4)–shell(PCHD‐1,2) cylinders in PS matrix and three‐phase (PS, PCHD‐1,4, PCHD‐1,2) four‐layer lamellae, were observed suggesting that the chain stiffness of the PCHD block and the strong dependence of the interaction parameter χ on the PCHD microstructures are important factors for the formation of this unusual microphase separation behavior in PS‐b‐PCHD diblock copolymers. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 1564–1572