bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of left ventricular stretching in model cultivations with neonatal cardiomyocytes in a whole‐heart bioreactor
Authors: Hülsmann Jörn , Aubin Hug , Wehrmann Alexander , Lichtenberg Artur , Akhyari Payam
Published: December 2016

Here, we investigate the impact of integrated three‐dimensional (3D) left ventricular (LV) stretching on myocardial maturation in a whole‐heart bioreactor setting. Therefore, decellularized rat hearts were selectively repopulated with rodent neonatal cardiomyocytes (5 · 106 cells per heart) and cultured over 5 days. Continuous medium perfusion was maintained through the coronary artery system in a customized whole‐heart bioreactor system with or without integrated biomechanical stimulation of LV. 3D repopulation effectiveness and cellular vitality were evaluated by repetitive metabolic WST‐1 assays and 3D confocal microscopy analysis through fluorescent staining, also assessing cellular organization. Moreover, specific myocardial vitality was verified by detecting spontaneous electrophysiological activity using a multielectrode assay. Western blot analysis of cardiac myosin heavychain (MHC) and quantitative RT‐PCR for Connexin 43 was used to analyze cardiomyocyte maturation. Decellularized whole‐heart constructs repopulated with neonatal cardiomyocytes (repopWHC) showed vital 3D cell populations throughout the repopulation sites within the LV with a significant increase in metabolic activity (326 ± 113% for stimulated constructs vs. 162 ± 32% for non‐stimulated controls after 96 h of continuous cultivation as compared to their state 24 h after injection, directly prior to bioreactor cultivation). Further, bioreactor cultivation under integrated mechanical LV stimulation not only led to a higher degree of cellular organization and an increased MHC content, but also to a significant increase of Cx43 gene expression resulting in a regain of 60 ± 19% of native neonatal hearts expression level in contrast to 20 ± 9% for non‐stimulated controls (P = 0.03). Therefore, our study suggests that the integration of LV stretching into whole‐heart bioreactor cultivation may enhance cardiac maturation not only by promoting cellular organization but also through adaptive protein and gene expression with particular implications for the formation of the conductive apparatus. Further, this study emphasizes the importance of suitable bioprocessing strategies within sophisticated bioreactor systems as tools for customized stimulation and cultivation of tissue engineered tissues and organs. Biotechnol. Bioeng. 2017;114: 1107–1117. © 2016 Wiley Periodicals, Inc.
Engineering the N‐terminal end of CelA results in improved performance and growth of Caldicellulosiruptor bescii on crystalline cellulose
Authors: Kim Sun‐Ki , Chung Daehwan , Himmel Michael E. , Bomble Yannick J. , Westpheling Janet
Published: December 2016

CelA is the most abundant enzyme secreted by Caldicellulosiruptor bescii and has been shown to outperform mixtures of commercially available exo‐ and endoglucanases in vitro. CelA contains both a glycoside hydrolase family 9 endoglucanase and a glycoside hydrolase family 48 exoglucanase known to be synergistic in their activity, connected by three cellulose‐binding domains via linker peptides. Here, repeated aspartate residues were introduced into the N‐terminal ends of CelA GH9 and GH48 domains to improve secretion efficiency and/or catalytic efficiency of CelA. Among several constructs, the highest activity on carboxymethylcellulose (CMC), 0.81 ± 0.03 mg/mL was observed for the C. bescii strain containing CelA with 5‐aspartate tag at the N‐terminal end of GH9 domain—an 82% increase over wild type CelA. In addition, expression of CelA with N‐terminal repeated aspartate residues in C. bescii results in a dramatic increase in its ability to grow on Avicel. Biotechnol. Bioeng. 2017;114: 945–950. © 2016 Wiley Periodicals, Inc.
Enantiomeric resolution, stereochemical assignment and toxicity evaluation of TPA enantiomers
Authors: Chi Yulang , Wu Zhijun , Zhong Yi , Dong Sijun
Published: December 2016

Tetrahydro‐α‐(1‐methylethyl)‐2‐oxo‐1(2H)‐pyrimidineacetic acid (TPA) is a critical intermediate in the synthesis of HIV protease inhibitors. A simple and efficient method for the separation and determination of TPA enantiomers was developed. The TPA was separated into its enantiomers with an enantiomeric purity of 99% using an HPLC system equipped with a Chiralpak OD‐H column. Semi‐preparative HPLC enantioseparations were carried out for further enrichment of the enantiomers. The validity of this method was evaluated on the basis of its precision, accuracy, linearity and recovery. The method was observed to be suitable for the rapid separation and semi‐preparation of TPA isomers. The separated enantiomers were identified by optical rotation and high‐resolution electrospray ionization mass spectrometry. Furthermore, the stereochemical structures of the TPA enantiomers were definitively confirmed using a combination of experimental and calculated electronic circular dichroism spectra. The toxicity of the separated pure enantiomers against Oryzias melastigma was evaluated using the median lethal concentration (LC50) values. The results indicated that (S)‐(−)‐TPA is ~2.5 times more toxic than its enantiomorphism.
General solutions to decompose heterogeneous compositions using antibody afucosylation as a model system
Authors: Chung John D. , Zhan Peter L.
Published: December 2016

Methods involving the use of mathematical models of competitive ligand—receptor binding to characterize mixtures of ligands in terms of compositions and properties of the component ligands have been developed. The associated mathematical equations explicitly relate component ligand physical–chemical properties and mole fractions to measurable properties of the mixture including steady state binding activity, 1/Kd,apparent or equivalently 1/EC50, and kinetic rate constants kon,apparent and koff,apparent allowing: (1) component ligand physical property determination and (2) mixture property predictions. Additionally, mathematical equations accounting for combinatorial considerations associated with ligand assembly are used to compute ligand mole fractions. The utility of the methods developed is demonstrated using published experimental ligand–receptor binding data obtained from mixtures of afucosylated antibodies that bind FcγRIIIa (CD16a) to: (1) extract component ligand physical property information that has hitherto evaded researchers, (2) predict experimental observations, and (3) provide explanations for unresolved experimental observations. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:500–510, 2017
Mammalian cell culture monitoring using in situ spectroscopy: Is your method really optimised?
Authors: André Silvère , Lagresle Sylvain , Hannas Zahia , Calvosa Éric , Duponchel Ludovic
Published: December 2016

In recent years, as a result of the process analytical technology initiative of the US Food and Drug Administration, many different works have been carried out on direct and in situ monitoring of critical parameters for mammalian cell cultures by Raman spectroscopy and multivariate regression techniques. However, despite interesting results, it cannot be said that the proposed monitoring strategies, which will reduce errors of the regression models and thus confidence limits of the predictions, are really optimized. Hence, the aim of this article is to optimize some critical steps of spectroscopic acquisition and data treatment in order to reach a higher level of accuracy and robustness of bioprocess monitoring. In this way, we propose first an original strategy to assess the most suited Raman acquisition time for the processes involved. In a second part, we demonstrate the importance of the interbatch variability on the accuracy of the predictive models with a particular focus on the optical probes adjustment. Finally, we propose a methodology for the optimization of the spectral variables selection in order to decrease prediction errors of multivariate regressions. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:308–316, 2017
An innovative model for integrating substance use treatment in schools
Authors: Ladegard Kristie , Ingram Amanda , Benningfield Margaret
Published: December 2016

Since legalization of marijuana in Colorado, youth marijuana use increased by 20%, which is 74% higher than the national average (National Survey on Drug Use and Health [NSDUH]). According to this same survey, the top 20 states with the highest rate of marijuana use for youth ages 12–17 years are those that have medical marijuana or have legalized recreational marijuana.
Keep your eye on …
Authors: Knopf Alison
Published: December 2016

New funding for mental health treatment

Harbingers of new‐onset MDD in children and teens

Trends in drug use by 8th, 10th, and 12th graders
Inability to pay for opioid use disorder treatment is main reason young adults don't get it
Authors: Knopf Alison
Published: December 2016

“Treatment on demand” is the watch call for helping young people who are misusing prescription opioids. But few of these young people do receive treatment, partly due to inability to pay, according to new research. Most alarmingly, a history of overdose was also correlated with an inability to access treatment.
A short but relevant history lesson
Authors: Fritz Gregory K.
Published: December 2016

I recently had the opportunity to learn more about the National Mental Health Association — now called Mental Health America — which caused me to reflect on the progress we have made in the United States regarding the treatment of the mentally ill. The occasion was the 100th anniversary of the Mental Health Association of Rhode Island (an affiliate of Mental Health America), where I was the recipient of The Bell Award. While I was honored to be the recipient, I didn't really know much about the Mental Health Association or this particular award. By the end of the evening, I was much more knowledgeable and somewhat wiser about a lot of history and where we fit into the evolution of mental treatment at this important juncture.
How to talk to your children about the election
Authors: Knopf Alison
Published: December 2016

“It's hard to be a parent tonight for a lot of us,” said Van Jones, a CNN political commentator, as the election returns were coming in during the early morning hours of Nov. 9, showing that Donald Trump was winning. “You tell your kids, ‘Don't be a bully.’ You tell your kids, ‘Don't be a bigot.’ You tell your kids, ‘Do your homework and be prepared,’” said Jones, who is black. “Then you have this outcome, and you have people putting children to bed tonight and they're afraid of breakfast.”
Night syncope: a case report
Authors: Loumaye Léopold , Blommaert Dominique
Published: December 2016

Key Clinical Message

“Idiopathic” ventricular fibrillations are rare and are estimated between 5% and 10% of survivors of hospital cardiac arrest, for at least some of them have as origin, a trigger in the Purkinje fibers. Interventional therapy could be an effective, long‐lasting solution for these recurrent malignant arrhythmias and should be considered.
Ambiguous subdural collection
Authors: Nakhla Jonathan , Bhashyam Niketh , Yassari Reza
Published: December 2016

Key Clinical Message

Prostate cancer metastasis to the dura is a rare occurrence. Metastasis to the dura can present as signs and symptoms of worsening mental status or neurological deficit. Therefore, malignant metastasis should be considered in a patient presenting with history of prostate cancer and worsening metal status without evidence of trauma.
Graphene Quantum Dots Decorated Titania Nanosheets Heterojunction: Efficient Charge Separation and Enhanced Visible‐Light Photocatalytic Performance
Authors: Bian Shiyue , Zhou Chenjuan , Li Peiran , Liu Jiyang , Dong Xiaoping , Xi Fengna
Published: December 2016

Titania nanosheets (TNSs) are of importance for photocatalytic application owing to the unique two‐dimensional (2D) morphology, high crystallinity and plentiful surface charge. However, the large band gap prohibited the efficient utilization of sun light. Herein, we employed graphene quantum dots (GQDs) as green photocatalytic promoter to decorate TNSs during the electrostatic flocculation. The obtained GQDs/TNSs heterojunction was systematically characterized, and the results demonstrated that the composite exhibited an intimate coupling of GQDs and TNSs, a markedly visible light absorption and therefore the enhanced separation efficiency of photogenerated charges. This composite photocatalyst shows enhanced photocatalytic performance for the photodegradation of Rhodamine B (RhB) under visible light irradiation in comparison with pure restacked TNSs (rs‐TNSs) and GQDs. Furthermore, this composite exhibited a superior reusability, and a high degradation ratio about 90 % was still achieved in the 5th cycle. Moreover, a possible mechanism was proposed and superoxide radicals, holes and hydroxyl radicals were determined as the active species.
A General Nickel‐Catalyzed Method for C−H Bond Alkynylation of Heteroarenes Through Chelation Assistance
Authors: Khake Shrikant M. , Soni Vineeta , Gonnade Rajesh G. , Punji Benudhar
Published: December 2016

A general nickel‐catalyzed method for the alkynylation of heteroarenes through monodentate chelation assistance is described. Many heterocycles, including indoles, pyrroles, imidazoles, and pyrazole, efficiently coupled with (triisopropylsilyl)alkynyl bromide, and synthetically important functional groups, such as halides, ether, nitrile, and nitro, are tolerated. Synthetic applicability of this Ni‐catalyzed method is demonstrated by the removal of the triisopropylsilyl group and further functionalization to triazolyl, benzofuranyl, and alkynyl arene derivatives. Preliminary mechanistic investigations of the alkynylation of indole suggest that the reaction proceeds through kinetically relevant C−H activation and follows a two‐electron redox pathway. A catalytically relevant Ni species, namely, [(Phen)3Ni]NiBr4 (PheN=1,10‐phenanthroline), was isolated and structurally characterized.
Cross‐conjugated Trienamine Catalysis with α′‐Alkylidene 2‐Cyclohexenones: Application in β,γ‐Regioselective Aza‐Diels–Alder Reaction
Authors: Zhou Zhi , Wang Zhou‐Xiang , Ouyang Qin , Xiao Wei , Du Wei , Chen Ying‐Chun
Published: December 2016

Endo‐type cross‐conjugated trienamines between highly congested α′‐alkylidene 2‐cyclohexenones and a chiral primary amine catalyst serve as HOMO‐raised dienophiles in inverse‐electron‐demand aza‐Diels–Alder cycloadditions with a number of 1‐azadiene substrates. The reactions exhibit exclusive β,γ‐regioselectivity, and multifunctional products with high molecular complexity are efficiently constructed in excellent diastereo‐ and enantioselectivity (>19:1 d.r., up to 99 % ee).
Study on the removal of fine particles by using water in a rotating packed bed
Authors: Li Ze‐Yan , Dong Kun , Liang Yan , Zhang Lili , Sun Baochang , Chu Guang‐Wen , Zou Hai‐Kui , Chen Jian‐Feng
Published: December 2016

This study presented an experimental investigation on the capture of fine particles from gas stream by water in a rotating packed bed (RPB). Experiments were carried out to investigate the effects of different operating conditions including packing types, rotation speed, gas‐liquid volumetric ratio, inlet particle concentration, and gas temperature on the removal efficiency of fine particles. The overall removal efficiency of fine particles can reach 98 % under the optimal operating conditions, which are a rotation speed of 1200 rpm, a gas‐liquid volumetric ratio of 600, a gas temperature of 100 °C, and the use of fine metal gauze packing. In addition, the correlation of removal efficiency of fine particles was deduced. It is observed that the predicted removal efficiency and outlet concentration of fine particles are in good agreement with the experimental values, with deviations within 10 % and 20 % respectively. This process exhibits the potential application of RPBs in simultaneous removal of fine particles and SO2 by liquid solution.
Quantitative validation of anti‐PTBP1antibody for diagnostic neuropathology use: Image analysis approach
Authors: Goceri Evgin , Goksel Behiye , Elder James B. , Puduvalli Vinay K. , Otero Jose J. , Gurcan Metin N.
Published: December 2016

Traditional diagnostic neuropathology relies on subjective interpretation of visual data obtained from a brightfield microscopy. This approach causes high variability, unsatisfactory reproducibility, and inability for multiplexing even among experts. These problems may affect patient outcomes and confound clinical decision‐making. Also, standard histological processing of pathological specimens leads to auto‐fluorescence and other artifacts, a reason why fluorescent microscopy is not routinely implemented in diagnostic pathology. To overcome these problems, objective and quantitative methods are required to help neuropathologists in their clinical decision‐making. Therefore, we propose a computerized image analysis method to validate anti‐PTBP1 antibody for its potential use in diagnostic neuropathology. Images were obtained from standard neuropathological specimens stained with anti‐PTBP1 antibody. First, the noise characteristics of the images were modeled and images are de‐noised according to the noise model. Next, images are filtered with sigma‐adaptive Gaussian filtering for normalization, and cell nuclei are detected and segmented with a k‐means–based deterministic approach. Experiments on 29 data sets from 3 cases of brain tumor and reactive gliosis show statistically significant differences between the number of positively stained nuclei in images stained with and without anti‐PTBP1 antibody. The experimental analysis of specimens from 3 different brain tumor groups and 1 reactive gliosis group indicates the feasibility of using anti‐PTBP1 antibody in diagnostic neuropathology, and computerized image analysis provides a systematic and quantitative approach to explore feasibility.
Theoretical Evaluation of Terahertz Sources Generated From SnGa4Q7 (Q=S, Se) as Infrared Nonlinear Optical Materials
Authors: Cheng Wen‐Dan , Lin Chen‐Sheng , Zhang Hao , Huang Yi‐Zhi , Chai Guo‐Liang
Published: December 2016

We theoretically evaluated the integrated knowledge that contributes to conversion efficiency, including the phonon, photon, and electron properties of infrared nonlinear optical materials such as SnGa4Q7 (Q=S, Se), which are terahertz (THz) sources. Specifically, we developed a new formula to calculate the susceptibility of the difference frequency generation (DFG) optical process. By evaluating the characteristics of the materials themselves in the THz region, we found that a larger nonlinear susceptibility or a large figure of merit resulted in a large efficiency of the THz source by comparing the findings of SnGa4Se7 and SnGa4S7 under the same experimental conditions; furthermore, THz absorption was found to reduce the efficiency of the THz source for the two SnGa4Q7 (Q=S, Se) materials. The efficiency of the THz source also depended on the experimental conditions. A large crystal size, strong pump intensity, and small THz wavelength resulted in better efficiency of the THz source based on the DFG process. The efficiency was found to be a comprehensive index to evaluate the THz source based on the DFG process.
Accuracy of international ultrasound risk stratification systems in thyroid lesions cytologically classified as indeterminate
Authors: Trimboli Pierpaolo , Fulciniti Franco , Zilioli Valentina , Ceriani Luca , Giovanella Luca
Published: December 2016

Background

Eminent international societies have published their thyroid ultrasound risk stratification system (US‐RSS) to give a friendly tool for thyroidologists. In particular, American Thyroid Association (ATA), American Association Clinical Endocrinologists/American College of Endocrinologists and Associazione Medici Endocrinologi (AACE/ACE/AME), British Thyroid Association (BTA), and Thyroid Imaging Reporting and Data System (TIRADS) are often adopted for clinical practice. The reliability of these US‐RSS has not been evaluated in discriminating cancers from benignancy in nodules with indeterminate FNA.

Methods

Indeterminate thyroid lesions were searched in our database and only those with histology were finally included. The matching of US and histologic data of nodule's location and size were verified. All US images and clips were re‐evaluated and nodules classified according to the above US‐RSS.

Results

A series of 101 indeterminate lesions, diagnosed by FNA were included (mean size 2.4 cm) and a 21% of cancers was found at histology. When all lesions were classified by US‐RSS, poor accuracy (up to 54%) and specificity (up to 19%) were recorded. Highest sensitivity (91%) and NPV (94%) was obtained by BTA. Of relevance, the rate of nodules with indeterminate US risk recorded by BTA was significantly lower than the other (P < 0.001). At nodule's size analysis, cancers had significantly higher estimated volume (P < 0.05). When we considered the size thresholds proposed by guidelines, ATA system reached the highest sensitivity in detecting cancers (95%).

Conclusions

Even if international US‐RSS have suboptimal accuracy in indeterminate thyroid nodules, high sensitivity can be obtained using ATA system with specific dimensional cut‐offs. Diagn. Cytopathol. 2017;45:113–117. © 2016 Wiley Periodicals, Inc.
The importance of EZH2 and MOC‐31 expression in the differential diagnosis of benign and malignant effusions
Authors: Sadullahoglu Canan , Nart Deniz , Veral Ali
Published: December 2016

Background

All malignant tumors may spread throughout the pleural, peritoneal, and pericardial cavities. The presence of tumor cells in serosal fluid is a poor prognostic indicator. It may be difficult to differentiate nuclear atypia of mesothelial cells due to injury of serosal surfaces from mesothelioma or malignant epithelial tumor cells. Epithelial and mesothelial immunohistochemical markers can be used in such conditions. The aim of this study was to evaluate the expression of two immunohistochemical markers (MOC‐31 and EZH2) in serosal effusions.

Methods

The study included a total of 142 patients diagnosed with benign or malignant cytology between January 2012 and April 2014. MOC‐31 and EZH2 were applied to the cell blocks of 53 patients with benign cytology and 89 patients with malignant cytology determined based on the clinical, radiological data, histopathology diagnosis, and clinical follow‐up in the absence of any surgical material of the patient in the hospital archive system.

Results

None of the benign cases showed MOC‐31 and EZH2 expression, although these markers were positive in 96 and 93% respectively of the malignant cases.

Conclusion

In conclusion, it could be considered cost‐effective to use a double immunohistochemical antibody kit for these two markers, MOC‐31 membranous and EZH2 nuclear staining, in the diagnosis of malignant effusions. Diagn. Cytopathol. 2017;45:118–124. © 2016 Wiley Periodicals, Inc.
Evaluation of KIMS immunoassays on a cobas c 501 analyzer for drugs of abuse and ethyl glucuronide testing in urine for forensic abstinence control
Authors: Neukamm Merja A. , Bahrami Arsham , Auwärter Volker , Mehne Felix M.P. , Höss Eva
Published: December 2016

For the medico‐psychological assessment (MPA) during driving licence re‐granting in Germany, abstinence control including urine samples is required. In these programmes, even small amounts of markers for drug or alcohol abuse have to be detected. Thus, the concentrations of the target compounds are very low, and, in consequence, the sensitivity of the applied screening method has to be much higher than for clinical use. Modified drugs of abuse and ethyl glucuronide immunoassays on a Roche cobas c 501 analyzer were evaluated for precision, accuracy, onboard calibration stability, cross reactivity, sensitivity, and specificity using authentic urine samples. Precision (intra‐day and inter‐day relative standard deviation (RSD) and accuracy (bias) at three concentrations were 12% or lower for all parameters. The calibrations remained stable (deviations <25%) for at least 28 days for all assays except amphetamines (21 days). Satisfactory cross reactivity was determined for the relevant analytes and also for several new psychoactive substances (NPS). The sensitivity was 100% for all parameters except methadone metabolite EDDP (92%) and fully met the sensitivity criteria for MPA urine testing. The presented kinetic interaction of microparticles in a solution (KIMS) immunoassays on a cobas c 501 thus provide a new method to reliably detect drug or alcohol consumption in abstinence control programmes requiring high sensitivity. Copyright © 2016 John Wiley & Sons, Ltd.
Increased pollinator habitat enhances cacao fruit set and predator conservation
Authors: Forbes Samantha J. , Northfield Tobin D.
Published: December 2016

The unique benefits of wild pollinators to the productivity of agricultural crops have become increasingly recognized in recent decades. However, declines in populations of wild pollinator species, largely driven by the conversion of natural habitat to agricultural land and broad‐spectrum pesticide use often lead reductions in the provision of pollination services and crop production. With growing evidence that targeted pollinator conservation improves crop yield and/or quality, particularly for pollination specialist crops, efforts are increasing to substitute agriculturally intensive practices with those that alleviate some of the negative impacts of agriculture on pollinators and the pollination services they provide, in part through the provision of suitable pollinator habitat. Further, similarities between the responses of some pollinators and predators to habitat management suggest that efforts to conserve pollinators may also encourage predator densities. We evaluated the effects of one habitat management practice, the addition of cacao fruit husks to a monoculture cacao farm, on the provision of pollination services and the densities of two groups of entomophagous predators. We also evaluated the impacts of cacao fruit husk addition on pollen limitation, by crossing this habitat manipulation with pollen supplementation treatments. The addition of cacao fruit husks increased the number of fruits per tree and along with hand pollination treatments, increased final yields indicating a promotion of the pollination ecosystem service provided by the specialist pollinators, midges. We also found that cacao fruit husk addition increased the densities of two predator groups, spiders and skinks. Further, the conservation of these predators did not inhibit pollination through pollinator capture or deterrence. The findings show that, with moderate habitat management, both pollinator and predator conservation can be compatible goals within a highly specialized plant–pollinator system. The effectiveness of this habitat manipulation may be attributable to the increased availability of alternative habitat and food resources for both pollinators and predators. The results exemplify a win‐win relationship between agricultural production and biological conservation, whereby agricultural practices to support vital pollinators and pollination services can increase production as well as support species conservation.
β‐Diketones as Scaffolds for Anticancer Drug Design – From Organic Building Blocks to Natural Products and Metallodrug Components
Authors: Kljun Jakob , Turel Iztok
Published: December 2016

The β‐diketone scaffold is a key intermediate in the synthesis of COX‐2 inhibitors, a type of non‐steroidal anti‐inflammatory agents of the coxib family, which have also been shown to have excellent anticancer potential at the preclinical stage of research. Moreover, it is also present in the family of natural products named curcuminoids. Both natural products and their synthetic analogues possess interesting antibacterial, neuroprotective and anticancer properties. Coordination compounds of curcuminoids with platinum‐group metals as potential anticancer agents are a hot topic of current research, with most scientific articles on this topic having been published in the last five years. Structurally simpler diketones, such as acetylacetone derivatives, are also employed in the design of new metal‐based agents. Most notably, the first metal‐based, non‐platinum anticancer compound to enter clinical trials was budotitane – cis‐diethoxy(1‐phenylbutane‐1,3‐dionato)titanium(IV). Recently, several studies of platinum‐group coordination and organometallic compounds, their biological evaluation and mode‐of‐action studies have been published in high‐impact journals in the field of inorganic and medicinal chemistry.
Antimicrobial activity of Fe‐loaded chitosan nanoparticles
Authors: Qian Junqing , Pan Cunli , Liang Changhai
Published: December 2016

To increase the antimicrobial activities of chitosan, chitosan nanoparticles loaded with Fe2+ or Fe3+ were prepared by surfactant‐assisted chitosan chelating Fe2+, Fe3+ and ionic gelation chitosan. Their chelating rates were determined by spectrophotometry. The particle sizes and zeta potentials of chitosan nanoparticles loaded with Fe2+ or Fe3+ were measured by size and zeta potential analysis. The nanoparticles antimicrobial activities were evaluated by different concentration against Escherichia coli, Staphylococcus aureus, Candida albicans in vitro. Results showed that the mean diameter of chitosan nanoparticles loaded with Fe2+ or Fe3+ were 206.4 and 195.2 nm, respectively. Their zeta potentials were +28.82 and +28.26 mV, respectively. The chelating rate of chitosan nanoparticles loaded with Fe2+ was greatly higher than with Fe3+. Their antimicrobial activity was showed greatly higher at lower concentrations compared to chitosan, and the antibacterial effect of chitosan nanoparticles loaded with Fe2+ or Fe3+ was preliminary observed.
Acute sensitivity of the vernal pool fairy shrimp, Branchinecta lynchi (Anostraca; Branchinectidae), and surrogate species to 10 chemicals
Authors: Ivey Chris D. , Besser John M. , Ingersoll Chris G. , Wang Ning , Rogers D. Christopher , Raimondo Sandy , Bauer Candice R. , Hammer Edward J.
Published: December 2016

Vernal pool fairy shrimp, Branchinecta lynchi, (Branchiopoda; Anostraca) and other fairy shrimp species have been listed as threatened or endangered under the US Endangered Species Act. Because few data exist about the sensitivity of Branchinecta spp. to toxic effects of contaminants, it is difficult to determine whether they are adequately protected by water quality criteria. A series of acute (24-h) lethality/immobilization tests was conducted with 3 species of fairy shrimp (B. lynchi, Branchinecta lindahli, and Thamnocephalus platyurus) and 10 chemicals with varying modes of toxic action: ammonia, potassium, chloride, sulfate, chromium(VI), copper, nickel, zinc, alachlor, and metolachlor. The same chemicals were tested in 48-h tests with other branchiopods (the cladocerans Daphnia magna and Ceriodaphnia dubia) and an amphipod (Hyalella azteca), and in 96-h tests with snails (Physa gyrina and Lymnaea stagnalis). Median effect concentrations (EC50s) for B. lynchi were strongly correlated (r2 = 0.975) with EC50s for the commercially available fairy shrimp species T. platyurus for most chemicals tested. Comparison of EC50s for fairy shrimp and EC50s for invertebrate taxa tested concurrently and with other published toxicity data indicated that fairy shrimp were relatively sensitive to potassium and several trace metals compared with other invertebrate taxa, although cladocerans, amphipods, and mussels had similar broad toxicant sensitivity. Interspecies correlation estimation models for predicting toxicity to fairy shrimp from surrogate species indicated that models with cladocerans and freshwater mussels as surrogates produced the best predictions of the sensitivity of fairy shrimp to contaminants. The results of these studies indicate that fairy shrimp are relatively sensitive to a range of toxicants, but Endangered Species Act-listed fairy shrimp of the genus Branchinecta were not consistently more sensitive than other fairy shrimp taxa. Environ Toxicol Chem 2017;36:797–806. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.
Mixture toxicity of phostebupirim and cyfluthrin: Species-specific responses
Authors: de Perre Chloe , Murphy Tracye M. , Lydy Michael J.
Published: December 2016

Currently, the potential impact of insecticide mixtures to nontarget organisms is largely unknown, and additional study is needed. The present study investigated the mixture toxicity of the organophosphate insecticide phostebupirim and the pyrethroid insecticide cyfluthrin using 4 nontarget species including Daphnia magna, Hyalella azteca, Pimephales promelas (fathead minnow), and Danio rerio (zebrafish). For each species, the toxicity of equipotent mixtures was compared with the expected toxicity estimated using the independent action (IA) and concentration addition (CA) models. Lethal and sublethal responses to D. magna and H. azteca were best described with the IA model. For both fish species, mixture toxicity was significantly higher than that estimated using either mixture model. The synergism noted in fish exposed to the combination of phostebupirim and cyfluthrin was confirmed by exposing P. promelas larvae to a nontoxic dose of phostebupirim and a range of toxic cyfluthrin concentrations, and vice versa. Sublethal and lethal concentrations to fish were up to 7 times lower for the mixture than in concurrently run individual compound exposures. Potential mechanisms for the synergistic responses found in fish are presented. Environ Toxicol Chem 2017;36:1947–1954. © 2016 SETAC
Societal stability and environmental change: Examining the archaeology‐soil erosion paradox
Authors: Brown Antony G. , Walsh Kevin
Published: December 2016

This paper critically examines the soil exhaustion and societal collapse hypothesis both theoretically and empirically. The persistence of civilizations, especially in the Mediterranean, despite intensive and presumably erosive arable farming creates what is described here as the archaeology soil erosion paradox. This paper examines the data used to estimate past erosion and weathering rates before presenting case studies that engage with the theoretical arguments. Study 1 shows 5000 years of high slope erosion rates with both soil use and agriculture continuously maintained in the catchment. Study 2 shows how ancient agricultural terraces were constructed as part of an integrated agricultural system that fed the ancient city of Stymphalos—now abandoned. Study 3 presents a recent example of how after the removal of terraces high soil erosion rates result during intense rainstorms but that arable agriculture can still be maintained while external costs are borne by other parties. What these case studies have in common is the creation of soil, and increased weathering rates while productivity is maintained due to a combination of soft bedrock and/or agricultural terraces. In societal terms this may not be sustainable but it does not necessarily lead to land abandonment or societal collapse.
Impact of genotyping errors on statistical power of association tests in genomic analyses: A case study
Authors: Hou Lin , Sun Ning , Mane Shrikant , Sayward Fred , Rajeevan Nallakkandi , Cheung Kei‐Hoi , Cho Kelly , Pyarajan Saiju , Aslan Mihaela , Miller Perry , Harvey Philip D. , Gaziano J. Michael , Concato John , Zhao Hongyu
Published: December 2016

A key step in genomic studies is to assess high throughput measurements across millions of markers for each participant's DNA, either using microarrays or sequencing techniques. Accurate genotype calling is essential for downstream statistical analysis of genotype‐phenotype associations, and next generation sequencing (NGS) has recently become a more common approach in genomic studies. How the accuracy of variant calling in NGS‐based studies affects downstream association analysis has not, however, been studied using empirical data in which both microarrays and NGS were available. In this article, we investigate the impact of variant calling errors on the statistical power to identify associations between single nucleotides and disease, and on associations between multiple rare variants and disease. Both differential and nondifferential genotyping errors are considered. Our results show that the power of burden tests for rare variants is strongly influenced by the specificity in variant calling, but is rather robust with regard to sensitivity. By using the variant calling accuracies estimated from a substudy of a Cooperative Studies Program project conducted by the Department of Veterans Affairs, we show that the power of association tests is mostly retained with commonly adopted variant calling pipelines. An R package, GWAS.PC, is provided to accommodate power analysis that takes account of genotyping errors (http://zhaocenter.org/software/).
Integration of gene expression and methylation to unravel biological networks in glioblastoma patients
Authors: Gadaleta Francesco , Bessonov Kyrylo , Van Steen Kristel
Published: December 2016

The vast amount of heterogeneous omics data, encompassing a broad range of biomolecular information, requires novel methods of analysis, including those that integrate the available levels of information. In this work, we describe Regression2Net, a computational approach that is able to integrate gene expression and genomic or methylation data in two steps. First, penalized regressions are used to build Expression‐Expression (EEnet) and Expression‐Genomic or Expression‐Methylation (EMnet) networks. Second, network theory is used to highlight important communities of genes. When applying our approach, Regression2Net to gene expression and methylation profiles for individuals with glioblastoma multiforme, we identified, respectively, 284 and 447 potentially interesting genes in relation to glioblastoma pathology. These genes showed at least one connection in the integrated networks ANDnet and XORnet derived from aforementioned EEnet and EMnet networks. Although the edges in ANDnet occur in both EEnet and EMnet, the edges in XORnet occur in EMnet but not in EEnet. In‐depth biological analysis of connected genes in ANDnet and XORnet revealed genes that are related to energy metabolism, cell cycle control (AATF), immune system response, and several cancer types. Importantly, we observed significant overrepresentation of cancer‐related pathways including glioma, especially in the XORnet network, suggesting a nonignorable role of methylation in glioblastoma multiforma. In the ANDnet, we furthermore identified potential glioma suppressor genes ACCN3 and ACCN4 linked to the NBPF1 neuroblastoma breakpoint family, as well as numerous ABC transporter genes (ABCA1, ABCB1) suggesting drug resistance of glioblastoma tumors.
Quantification of peatland water storage capacity using the water table fluctuation method
Authors: Bourgault Marc‐André , Larocque Marie , Garneau Michelle
Published: December 2016

Peat specific yield (SY) is an important parameter involved in many peatland hydrological functions such as flood attenuation, baseflow contribution to rivers, and maintaining groundwater levels in surficial aquifers. However, general knowledge on peatland water storage capacity is still very limited, due in part to the technical difficulties related to in situ measurements. The objectives of this study were to quantify vertical SY variations of water tables in peatlands using the water table fluctuation (WTF) method and to better understand the factors controlling peatland water storage capacity. The method was tested in five ombrotrophic peatlands located in the St. Lawrence Lowlands (southern Québec, Canada). In each peatland, water table wells were installed at three locations (up‐gradient, mid‐gradient, and down‐gradient). Near each well, a 1‐m long peat core (8 cm × 8 cm) was sampled, and subsamples were used to determine SY with standard gravitational drainage method. A larger peat sample (25 cm × 60 cm × 40 cm) was also collected in one peatland to estimate SY using a laboratory drainage method. In all sites, the mean water table depth ranged from 9 to 49 cm below the peat surface, with annual fluctuations varying between 15 and 29 cm for all locations. The WTF method produced similar results to the gravitational drainage experiments, with values ranging between 0.13 and 0.99 for the WTF method and between 0.01 and 0.95 for the gravitational drainage experiments. SY was found to rapidly decrease with depth within 20 cm, independently of the within‐site location and the mean annual water table depth. Dominant factors explaining SY variations were identified using analysis of variance. The most important factor was peatland site, followed by peat depth and seasonality. Variations in storage capacity considering site and seasonality followed regional effective growing degree days and evapotranspiration patterns. This work provides new data on spatial variations of peatland water storage capacity using an easily implemented method that requires only water table measurements and precipitation data.
Effect on surface character and mechanical property of unsintered hydroxyapatite/poly‐l‐lactic acid (uHA/PLLA) material by UV treatment
Authors: Moroi Akinori , Okuno Masaki , Kobayashi Go , Gamo Hitoshi , Serizawa Izumi , Yoshizawa Kunio , Ikawa Hiroumi , Ueki Koichiro
Published: December 2016

Materials fabricated with unsintered hydroxyapatite/poly‐l‐lactic acid (uHA/PLLA) exhibit biological activity and biocompatibility, but are also hydrophobic. This hydrophobicity limits the ability of cells or tissues to adhere to the surface of the material and thereby prevents the materials from exhibiting effective biological activity. In this study, we examined the effects of ultraviolet (UV) treatment on the hydrophobicity of uHA/PLLA. We compared the contact angle, mechanical strength, cell attachment, and cell differentiation capacity between untreated uHA/PLLA and uHA/PLLA treated with UV light. The contact angle of UV‐treated uHA/PLLA was significantly reduced compared with that of untreated uHA/PLLA. However, there were no differences in mechanical strength between untreated uHA/PLLA and UV‐treated uHA/PLLA. Notably, the ability of cells to adhere to UV‐treated uHA/PLLA was significantly increased compared with that of untreated uHA/PLLA. Similarly, there were significant differences between UV‐treated uHA/PLLA and untreated uHA/PLLA in alkaline phosphatase assays. These findings demonstrated that UV irradiation of uHA/PLLA improved the surface hydrophilicity without changing the mechanical strength of the material; thus, UV treatment of uHA/PLLA may facilitate the use of this material in biomedical applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 191–200, 2018.
CRMP4 Inhibits Bone Formation by Negatively Regulating BMP and RhoA Signaling
Authors: Abdallah Basem M , Figeac Florence , Larsen Kenneth H , Ditzel Nicholas , Keshari Pankaj , Isa Adiba , Jafari Abbas , Andersen Thomas L , Delaisse Jean-Marie , Goshima Yoshio , Ohshima Toshio , Kassem Moustapha
Published: December 2016

We identified the neuroprotein collapsing response mediator protein-4 (CRMP4) as a noncanonical osteogenic factor that regulates the differentiation of mouse bone marrow skeletal stem cells (bone marrow stromal stem cells [mBMSCs]) into osteoblastic cells. CRMP4 is the only member of the CRMP1–CRMP5 family to be expressed by mBMSCs and in osteoprogenitors of both adult mouse and human bones. In vitro gain-of-function and loss-of-function of CRMP4 in murine stromal cells revealed its inhibitory effect on osteoblast differentiation. In addition, Crmp4-deficient mice (Crmp4–/–) displayed a 40% increase in bone mass, increased mineral apposition rate, and bone formation rate, compared to wild-type controls. Increased bone mass in Crmp4–/– mice was associated with enhanced BMP2 signaling and BMP2-induced osteoblast differentiation in Crmp4–/– osteoblasts (OBs). Furthermore, Crmp4–/– OBs exhibited enhanced activation of RhoA/focal adhesion kinase (FAK) signaling that led to cytoskeletal changes with increased cell spreading. In addition, Crmp4–/– OBs exhibited increased cell proliferation that was mediated via inhibiting cyclin-dependent kinase inhibitor 1B, p27Kip1 and upregulating cyclin D1 expression which are targets of RhoA signaling pathway. Our findings identify CRMP4 as a novel negative regulator of osteoblast differentiation. © 2016 American Society for Bone and Mineral Research.
Hairy and Enhancer of Split‐Related With YRPW Motif‐Like (HeyL) Is Dispensable for Bone Remodeling in Mice
Authors: Canalis Ernesto , Zanotti Stefano
Published: December 2016

Notch induces Hairy Enhancer of Split (Hes)1 and Hes‐related with YRPW motif (Hey) Hey1, Hey2 and Hey‐like (HeyL) expression in osteoblasts, but it is not known whether any of these target genes mediates the effect of Notch in the skeleton. We demonstrated that Notch1 activation in osteoblasts/osteocytes induces Hes1, Hey1, Hey2, and HeyL, but HeyL was induced to a greater extent than other target genes. To characterize HeyL null mice for their skeletal phenotype, microcomputed tomography (µCT) and histomorphometric analysis of HeyL null and sex‐matched littermate controls was performed. µCT demonstrated modest cancellous bone osteopenia in 1 month old male mice and normal microarchitecture in 3 month old male HeyL null mice. Female HeyL null mice were not different from controls at either 1 or 3 months of age. Bone histomorphometry did not demonstrate differences between HeyL null mice of either sex and littermate controls. In conclusion, HeyL null mice do not exhibit an obvious skeletal phenotype demonstrating that HeyL is dispensable for skeletal homeostasis. J. Cell. Biochem. 118: 1819–1826, 2017. © 2016 Wiley Periodicals, Inc.
Isolation, identification, and characterization of cancer stem cells: A review
Authors: Abbaszadegan Mohammad Reza , Bagheri Vahid , Razavi Mahya Shariat , Momtazi Amir Abbas , Sahebkar Amirhossein , Gholamin Mehran
Published: December 2016

Cancer stem cells (CSCs) or tumor‐initiating cells (TICs) as a small subset of neoplastic cells are able to produce a tumor (tumorigenesis), maintain the population of tumorigenic cells (self‐renewal), and generate the heterogeneous cells constructing the entire tumor (pluripotency). The research on stationary and circulating CSCs due to resistance to conventional therapies and inability in complete eradication of cancer is critical for developing novel therapeutic strategies for a more effective reduction in the risk of tumor metastasis and cancer recurrence. This review compiles information about different methods of detection and dissociation, side population, cellular markers, and establishment culture of CSCs, as well as characteristics of CSCs such as tumorigenicity, and signaling pathways associated with self‐renewal and the capability of the same histological tumor regeneration in various cancers.