bluuebunny/crossref_metadata_2025 huggingface dataset:
A Practical Cryopreservation and Staining Protocol for Immunophenotyping in Population Studies
Authors: Barcelo Helene , Faul Jessica , Crimmins Eileen , Thyagarajan Bharat
Published: April 2018

Large population‐based cohort studies, through their prospective collection of a broad range of health information, represent an invaluable resource for novel insights into the pathogenesis of human diseases. Collection and cryopreservation of viable cells from blood samples is becoming increasingly common in large cohorts as these cells are a valuable resource for immunophenotyping and functional studies. The cryopreservation of peripheral blood mononuclear cells (PBMCs), thawing, and immunophenotyping protocols used to immunophenotype 9938 participants in the Health and Retirement Study (HRS) are described. The extensive quality control involved in a large‐scale immunophenotyping epidemiological study is also outlined. The existing literature on the effect of cryopreservation on various immune cell subsets including T, B, NK cells, monocytes, and dendritic cells is provided. © 2018 by John Wiley & Sons, Inc.
A Prospective Randomized, Double‐Blind, Two‐Period Crossover Pharmacokinetic Trial Comparing Green Coffee Bean Extract—A Botanically Sourced Caffeine—With a Synthetic USP Control
Authors: Morton Kayce , Knight Katelin , Kalman Douglas , Hewlings Susan
Published: April 2018

Coffee is a primary dietary source of the chlorogenic acids (CGAs) of phenolic compounds. Coffee contains caffeine and other phytonutrients, including CGAs. Caffeine on its own has been well characterized and descried pharmacokinetically in the literature, less so for CGAs. The purpose of this double‐blind crossover study was to determine the comparative pharmacokinetics of CGAs with caffeine (natural extract) with synthetic caffeine (US Pharmacopeia [USP] standard). Sixteen healthy male subjects were randomly assigned to take 1 dose of product 1, 60 mg of botanically sourced caffeine from 480 mg of green coffee bean extract, or product 2, 60 mg of synthetic USP caffeine, with 5 days between. Blood analysis was done to determine the levels of CGA compounds, more specifically 3‐, 4‐, and 5‐caffeoylquinic acid (CQA), and serum caffeine. The natural caffeine extract exhibited mean peak concentrations (Cmax) of 3‐CQA (11.4 ng/mL), 4‐CQA (6.84 ng/mL), and 5‐CQA (7.20 ng/mL). The mean systemic 4‐hour exposure (AUC0–4 h) was 3‐CQA (27.3 ng·h/mL), 4‐CQA (16.1 ng·h/mL), and 5‐CQA (15.7 ng·h/mL). The median tmax was 3‐CQA (1.00 hour), 4‐CQA (1.00 hour), and 5‐CQA (1.50 hours). The tmax of caffeine was 0.75 hours (natural extract) and 0.63 hours (synthetic caffeine). Cmax and AUC0–4 h of serum caffeine were statistically equivalent between products. The geometric least‐squares mean ratios (GMRs) of Cmax and AUC0–4 h of caffeine were 97.77% (natural extract) and 98.33% (synthetic caffeine). It would appear that CGA compounds from the natural caffeine extract are bioavailable, and 3‐CGA may be the compound most absorbed. In addition, caffeine sourced from natural extract versus synthetic were statistically similar for pharmacokinetic parameters. There were no adverse events or safety concerns.
One‐Pot Synthesis of Diverse γ‐Lactam Scaffolds Facilitated by a Nebulizer‐Based Continuous Flow Photoreactor
Authors: Ioannou Georgios I. , Montagnon Tamsyn , Kalaitzakis Dimitris , Pergantis Spiros A. , Vassilikogiannakis Georgios
Published: April 2018

The use of a modified prototype continuous flow reactor (CFR) as a pivotal part of a number of versatile singlet oxygen‐mediated reaction sequences is presented herein. These sequences target rapid access to structural complexity and diversity. The prototype reactor achieves high conversions and productivities by attaining large specific surface areas for these biphasic reactions. In the reactor, the reaction solution is nebulized (using either oxygen or air) and the resulting aerosol is irradiated by an LED jacket that surrounds the Pyrex reaction chamber. The one pot procedures developed herein are, according to many different criteria, both highly efficient and green. The key common intermediates and the source of both the complexity and variety of the final products are N‐acyl imminium ions (NAI; protonated N‐acyl enamines). The initial substrates are simple and readily accessible furans and the diverse array of products is composed of different complex γ‐lactams. Many of the products are of particular interest due to their close relationships to known biologically active molecules.
Large‐scale distribution patterns of mangrove nematodes: A global meta‐analysis
Authors: Brustolin Marco C. , Nagelkerken Ivan , Fonseca Gustavo
Published: April 2018

Mangroves harbor diverse invertebrate communities, suggesting that macroecological distribution patterns of habitat‐forming foundation species drive the associated faunal distribution. Whether these are driven by mangrove biogeography is still ambiguous. For small‐bodied taxa, local factors and landscape metrics might be as important as macroecology. We performed a meta‐analysis to address the following questions: (1) can richness of mangrove trees explain macroecological patterns of nematode richness? and (2) do local landscape attributes have equal or higher importance than biogeography in structuring nematode richness? Mangrove areas of Caribbean‐Southwest Atlantic, Western Indian, Central Indo‐Pacific, and Southwest Pacific biogeographic regions. We used random‐effects meta‐analyses based on natural logarithm of the response ratio (lnRR) to assess the importance of macroecology (i.e., biogeographic regions, latitude, longitude), local factors (i.e., aboveground mangrove biomass and tree richness), and landscape metrics (forest area and shape) in structuring nematode richness from 34 mangroves sites around the world. Latitude, mangrove forest area, and forest shape index explained 19% of the heterogeneity across studies. Richness was higher at low latitudes, closer to the equator. At local scales, richness increased slightly with landscape complexity and decreased with forest shape index. Our results contrast with biogeographic diversity patterns of mangrove‐associated taxa. Global‐scale nematode diversity may have evolved independently of mangrove tree richness, and diversity of small‐bodied metazoans is probably more closely driven by latitude and associated climates, rather than local, landscape, or global biogeographic patterns.
Bacterial communities associated with honeybee food stores are correlated with land use
Authors: Donkersley Philip , Rhodes Glenn , Pickup Roger W. , Jones Kevin C. , Wilson Kenneth
Published: April 2018

Microbial communities, associated with almost all metazoans, can be inherited from the environment. Although the honeybee (Apis mellifera L.) gut microbiome is well documented, studies of the gut focus on just a small component of the bee microbiome. Other key areas such as the comb, propolis, honey, and stored pollen (bee bread) are poorly understood. Furthermore, little is known about the relationship between the pollinator microbiome and its environment. Here we present a study of the bee bread microbiome and its relationship with land use. We estimated bacterial community composition using both Illumina MiSeq DNA sequencing and denaturing gradient gel electrophoresis (DGGE). Illumina was used to gain a deeper understanding of precise species diversity across samples. DGGE was used on a larger number of samples where the costs of MiSeq had become prohibitive and therefore allowed us to study a greater number of bee breads across broader geographical axes. The former demonstrates bee bread comprises, on average, 13 distinct bacterial phyla; Bacteroidetes, Firmicutes, Alpha‐proteobacteria, Beta‐proteobacteria, and Gamma‐proteobacteria were the five most abundant. The most common genera were Pseudomonas, Arsenophonus, Lactobacillus, Erwinia, and Acinetobacter. DGGE data show bacterial community composition and diversity varied spatially and temporally both within and between hives. Land use data were obtained from the 2007 Countryside Survey. Certain habitats, such as improved grasslands, are associated with low diversity bee breads, meaning that these environments may be poor sources of bee‐associated bacteria. Decreased bee bread bacterial diversity may result in reduced function within hives. Although the dispersal of microbes is ubiquitous, this study has demonstrated landscape‐level effects on microbial community composition.
Short‐term response of a declining woodland bird assemblage to the removal of a despotic competitor
Authors: Davitt Galen , Maute Kimberly , Major Richard E. , McDonald Paul G. , Maron Martine
Published: April 2018

Interspecific aggression by the noisy miner (Manorina melanocephala), a highly despotic species, is homogenizing woodland avifaunas across eastern Australia. Although a native species, the noisy miner's aggressive exclusion of small birds is a Key Threatening Process under national law. Large‐scale removal of noisy miners has been proposed as a management response to this threat following increases in miner presence due to anthropogenic land use practices. We tested this proposal by experimentally removing noisy miners from eucalypt woodland remnants (16–49 ha), assigned randomly as control (n = 12) or treatment (miner removal) sites (n = 12). Standardized bird surveys were conducted before and after removal, and generalized linear mixed models were used to investigate the effect of miner removal on bird assemblage metrics. Despite removing 3552 noisy miners in three sessions of systematic shooting, densities of noisy miners remained similarly high in treatment and control sites, even just 14 days after their removal. However, there was evidence of an increase in richness and abundance of small birds in treatment sites compared to controls—an effect we only expected to see if noisy miner densities were drastically reduced. We suggest that miner removal may have reduced the ability of the recolonizing miners to aggressively exclude small birds, even without substantially reducing miner densities, due to the breakdown of social structures that are central to the species' despotic behaviour. However, this effect on small birds is unlikely to persist in the long term. Synthesis and applications: Despite evidence from other studies that direct removal of noisy miners can result in rapid and sustained conservation benefit for bird communities at small scales, our findings cast doubt on the potential to scale‐up this management approach. The circumstances under which direct control of noisy miners can be achieved remain unresolved.
Stability of two layers dielectric‐electrolyte microflow subjected to an alternating external electric field
Authors: Demekhin Evgeny A. , Ganchenko Georgy S. , Gorbacheva Ekaterina V. , Amiroudine Sakir
Published: April 2018

The stability of the electroosmotic flow of the two‐phase system electrolyte‐dielectric with a free interface in the microchannel under an external electric field is examined theoretically. The mathematical model includes the Nernst–Plank equations for the ion concentrations. The linear stability of the 1D nonstationary solution with respect to the small, periodic perturbations along the channel, is studied. Two types of instability have been highlighted. The first is known as the long‐wave instability and is connected with the distortion of the free charge on the interface. In the long‐wave area, the results are in good agreement with the ones obtained theoretically and experimentally in the literature. The second type of instability is a short‐wave and mostly connected with the disturbance of the electrolyte conductivity. The short‐wave type of instability has not been found previously in the literature and constitutes the basis and the strength of the present work. It is revealed that with the increase of the external electric field frequency, the 1D flow is stabilized. The dependence of the flow on the other parameters of the system is qualitatively the same as for the constant electric field.
Overview of recent advances in phosphorus recovery for fertilizer production
Authors: Günther Susanne , Grunert Michael , Müller Susann
Published: April 2018

This Mini Review gives an overview of and respective references for the current situation regarding global phosphorus reserves and the legal situation for P recovery using Germany as the model. Apart from the well‐known pilot up to industrial/full scale recovery techniques, emerging chemical and bio‐based P recovery techniques are named without claiming to be all‐encompassing. Special attention is paid to the biological systems for P recovery that reveal ways for use of renewable resources as raw materials. A few chemically based recovery techniques like AirPrex®, (Ostara)PEARL™, AshDec®, and RecoPhos® have already been used to recover P at a rate and quality which allows for its sale as a fertilizer. Many chemically based processes are at the stage of investigation on a pilot or laboratory scale, e.g. P‐RoC, LeachPhos, and Mephrec®. All of the biologically based technologies like P‐Bac are still at an early stage of research and show promising results. Of all recovered materials struvite, calcium phosphate and biological bound phosphorous seem to have the best plant availability. Although there is no ultimate “one fits all” technology, potential P‐recovery plant operators can choose from a wide range of techniques which will best fit local raw material availability, economic and ecological situation.
Bioaugmentation of anaerobic digesters treating lignocellulosic feedstock by enriched microbial consortia
Authors: Ozbayram Emine Gozde , Kleinsteuber Sabine , Nikolausz Marcell , Ince Bahar , Ince Orhan
Published: April 2018

Three different bioaugmentation cultures enriched from natural and engineered cellulolytic environments (cow and goat rumen, a biogas reactor digesting sorghum biomass) were compared for their enhancement potential on the anaerobic digestion of wheat straw. Methane yields were determined in batch tests using the Automatic Methane Potential Test System operated for 30 days under mesophilic conditions. All cultures had positive effects on substrate degradation, and higher methane yields were observed in the bioaugmented reactors compared to control reactors set up with standard inoculum. However, the level of enhancement differed according to the type of the enrichment culture. Methane yield in batch reactors augmented with 2% cow rumen derived enrichment culture was increased by only 6%. In contrast, reactors amended with 2% goat rumen derived enrichment culture or with the bioaugmentation culture obtained from the biogas reactor digesting sorghum biomass produced 27 and 20% more methane, respectively. The highest methane yield was recorded in reactors amended with 6% goat rumen derived enrichment culture, which represented an increase by 36%. The microbial communities were quite similar at the end of the batch tests independently of the bioaugmentation sources, indicating that the introduced microbial communities of the enrichment cultures did not dominate the reactors.
Preliminary report: Late seizure recurrence years after epilepsy surgery may be associated with alterations in brain tissue transcriptome
Authors: Jehi Lara , Yehia Lamis , Peterson Charissa , Niazi Farshad , Busch Robyn , Prayson Richard , Ying Zhong , Bingaman William , Najm Imad , Eng Charis
Published: April 2018

We recently proposed that the maturation of a new epileptic focus (epileptogenesis) may explain late seizure recurrences, starting months to years after resective epilepsy surgery. We explore here the hypothesis that inherent transcriptomic changes may distinguish such “late relapsers.” An in‐depth clinical review of 2 patients with recurrent seizures starting years after surgery is contrasted to 4 controls who remained seizure‐free postoperatively. This clinical analysis is combined with RNA sequencing from the resected brain tissue, followed by unsupervised hierarchical clustering, independent pathway analysis, and multidimensional scaling analysis. Late‐recurrence patients clustered apart from seizure‐free patients, with late recurrence patients clustering together in the central space, whereas the seizure‐free patients clustered together in the periphery. We utilized RNA‐seq to identify differentially expressed genes between late‐recurrence and seizure‐free samples. We found 29 annotated genes with statistically significant differential expression (q < 0.05). The top canonical pathways identified as distinctly separating the late‐recurrence patients from the seizure‐free patients included the intrinsic prothrombin activation pathway (p = 1.55E‐06), the complement system (p = 4.57E‐05), and the atherosclerosis signaling pathway (p = 4.57E‐05). Our observations suggest that late recurrences after epilepsy surgery may be influenced partly by differences in gene expression in neuroinflammatory and brain healing/remodeling pathways. Such a hypothesis needs to be validated in the future.
Investigation of antioxidant activities of Pleurotus ostreatus stored at different temperatures
Authors: Bakir Temelkan , Karadeniz Mertcan , Unal Sabri
Published: April 2018

In this study, the antioxidant capacity of oyster mushroom (Pleurotus ostreatus) stored in five different temperature environments was investigated by DPPH (1,1 diphenyl‐2‐picryl hydrazyl) radical scavenging method. The antioxidant capacity results of oyster mushroom extracts were examined by spectroscopic measurements and expressed as percent of inhibition. The IC50 values of mushroom samples were calculated with DPPH method using calibration equations, and change in antioxidant properties was also tried to decipher by SEM images. The IC50 values of Pleurotus ostreatus for four different concentrations were also found in h+20°C > inh+4°C> inh−10°C> inh−20°C> inh−40°C, respectively. As a conclusion, the temperature factor of oyster mushroom in the range of −40°C to +20°C storage conditions is directly proportional to the change of antioxidant properties. The results have shown the importance of logistics and storage conditions in preserving the antioxidant properties of oyster mushroom and similar food samples.
Stability of Golden redfish (Sebastes marinus) during frozen storage as affected by raw material freshness and season of capture
Authors: Dang Huong Thi Thu , Gudjonsdóttir María , Karlsdóttir Magnea G. , Van Nguyen Minh , Tómasson Tumi , Arason Sigurjon
Published: April 2018

Physicochemical changes of Icelandic golden redfish (Sebastes marinus) as affected by seasonal variation (June and November) and raw material freshness (processed 4 and 9 days postcatch) during frozen storage (at −25°C for 20 months) were studied to find optimal conditions for production of high‐quality frozen products. Thawing loss, cooking yield, and color of the fillets as well as chemical composition, water holding capacity, pH, total volatile basic nitrogen, lipid oxidation, and hydrolysis of the light and dark muscle were analyzed every 4 months of frozen storage. Lipid hydrolysis was the main degradation process in the light muscle, while the dark muscle was more affected by lipid oxidation. Fish caught in November showed greater instability in the analyzed parameters during storage than fish caught in June, which could be linked to differences in individual poly unsaturated fatty acids between the two seasons. The quality attributes of fish processed on day 9 were similar to fish processed 4 days postcatch, except slightly higher thawing loss and yellowness, were observed in fish processed 9 days postcatch. Stability of golden redfish through frozen storage was higher in the fish caught in June than in November.
Comparison of optimality systems for the optimal control of the obstacle problem
Authors: Harder Felix , Wachsmuth Gerd
Published: April 2018

We consider stationarity systems for the optimal control of the obstacle problem. The focus is on the comparison of several different systems which are provided in the literature. We obtain some novel results concerning the relations between these stationarity concepts.
The role of psychic distance in entry mode decisions: Magnifying the threat of opportunism or increasing the need for local knowledge?
Authors: Dow Douglas , Baack Daniel , Parente Ronaldo
Published: April 2018

Research Summary: With respect to entry mode decisions, psychic distance may play two contradictory roles. On one hand, the transaction cost perspective is concerned with opportunism. Psychic distance magnifies the threat of opportunism, which encourages higher levels of control by foreign firms. Conversely, the new internalization perspective emphasizes the role of complementary assets controlled by local entities. Distance increases the need to access local knowledge, which encourages firms to seek joint ventures. By adopting an experimental approach and measuring managers' a priori perceptions of distance, this article contributes to the literature by providing a more sophisticated approach for discriminating between these effects. The results indicate that distance magnifies the need for firms to access complementary assets; however, distance does not appear to magnify the threat of opportunism.

Managerial Summary: This article explores the role that psychic distance (i.e., differences across countries in culture, language, religion, etc.) plays in how firms enter foreign markets. Specifically, do they prefer wholly owned subsidiaries (WOS) or do they prefer to form joint ventures (JV) with local players? One perspective argues that firms are concerned about potential partners in a foreign market taking advantage of them; thus, they will prefer the greater control a WOS offers. Conversely, firms may simply recognize that these differences put them at a disadvantage and prefer a JV as a way to gain local knowledge. Our experiments indicate that the latter explanation dominates. When entering very different countries, managers seem to prefer JVs in order to access key local knowledge.
Metastasis‐associated lung adenocarcinoma transcript 1 as a common molecular driver in the pathogenesis of nonalcoholic steatohepatitis and chronic immune‐mediated liver damage
Authors: Sookoian Silvia , Flichman Diego , Garaycoechea Martin E. , San Martino Julio , Castaño Gustavo O. , Pirola Carlos J.
Published: April 2018

Long noncoding RNAs (lncRNAs) are functional molecules that orchestrate gene expression. To identify lncRNAs involved in nonalcoholic fatty liver disease (NAFLD) severity, we performed a multiscale study that included: (a) systems biology modeling that indicated metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) as a candidate lncRNA for exploring disease‐related associations, (b) translational exploration in the clinical setting, and (c) mechanistic modeling. MALAT1 liver profiling was performed in three consecutive phases, including an exploratory stage (liver samples from patients with NAFLD who were morbidly obese [n = 47] and from 13 individuals with normal liver histology); a replication stage (patients with NAFLD and metabolic syndrome [n =49]); and a hypothesis‐driven stage (patients with chronic hepatitis C and autoimmune liver diseases, [n = 65]). Liver abundance of MALAT1 was associated with NAFLD severity (P = 1 × 10–6); MALAT1 expression levels were up‐regulated 1.75‐fold (P = 0.029) and 3.6‐fold (P = 0.012) in patients with nonalcoholic steatohepatitis compared to those diagnosed with simple steatosis (discovery and replication set, respectively; analysis of covariance adjusted by age, homeostasis model assessment, and body mass index). Quantification of liver vascular endothelial growth factor A messenger RNA, a target of MALAT1, revealed a significant correlation between the two RNAs (R, 0.58; P = 5 × 10–8). Increased levels of MALAT1 were also associated with autoimmune liver diseases. Interactome assessment uncovered significant biological pathways, including Janus kinase‐signal transducers and activators of transcription and response to interferon‐γ. Conclusion: Deregulated expression of MALAT1 stratifies patients into the histologic phenotypes associated with NAFLD severity. MALAT1 up‐regulation seems to be a common molecular mechanism in immune‐mediated chronic inflammatory liver damage. This suggests that convergent pathophenotypes (inflammation and fibrosis) share similar molecular mediators. (Hepatology Communications 2018;2:654‐665)
Effects of attention during encoding on sex differences in object location memory
Authors: Barel Efrat
Published: April 2018

Attention plays a key role in memory processes and has been widely studied in various memory tasks. The role of attention in sex differences in object location memory is not clearly understood. In the present study, two experiments involving 186 participants and using an object array presented on paper were conducted to examine two encoding conditions: incidental and intentional. In each experiment, the participants were randomly assigned to divided versus full attention conditions. In the first experiment, which involved incidental encoding, women outperformed men in memorising location‐exchanged objects in both the full and in the divided attention condition. In the second experiment, which involved intentional encoding, women outperformed men in memorising location‐exchanged objects in the full attention condition, but not the divided attention condition. These findings deepen our knowledge regarding the role of attention in object location memory, specifically in terms of the conditions under which females have an advantage for detecting changes in an array of objects.
Embryo–fetal toxicity assessment of vonoprazan in rats and rabbits
Authors: Li Tianyi , Qiao Hongqun , Yue Peng , Cai Ming , He Xuejun
Published: April 2018

Vonoprazan is a new potassium‐competitive acid blocker to treat acid‐related diseases. However, its safety during pregnancy is unclear. The aim of the study was to investigate the potential reproductive toxicity on the embryo–fetal development of vonoprazan. Vonoprazan acetate was administered by intravenous injection to pregnant rats (0, 2, 6 and 20 mg kg–1 day–1) and rabbits (0, 1.2, 3.6 and 12 mg kg–1 day–1) during the organogenetic period (gestation day 6–15 [rats] and 6–18 [rabbits]). Maternal reproductive endpoints were evaluated, together with effects on fetal growth and morphological development. In rats, no treatment‐related effects were found in the highest dose group (20 mg kg–1) and the maternal plasma exposure was ≥50‐fold the expected clinical human exposure. However, in rabbits, dose‐related clinical signs (soft or liquid feces) occurred in the 12 mg kg–1 group, which was regarded as a maternal toxicity. Besides, decreased maternal weight gain also was considered as a minimal maternal toxicity. At 12 mg kg–1, delayed fetal ossification was found as evidence of embryo–fetal growth retardation, which was related to decreased fetal and placental weights. There was no maternal and developmental toxicity in the 1.2 and 3.6 mg kg–1 groups. Thus, the no‐observed‐adverse‐effect levels of vonoprazan acetate in rabbits are considered 3.6 mg kg–1 day–1, which produced plasma exposure that was about 18‐fold human clinical exposure.
Encapsulated oligodendrocyte precursor cell fate is dependent on PDGF‐AA release kinetics in a 3D microparticle‐hydrogel drug delivery system
Authors: Pinezich Meghan R. , Russell Lauren N. , Murphy Nicholas P. , Lampe Kyle J.
Published: April 2018

Biomaterial drug delivery systems (DDS) can be used to regulate growth factor release and combat the limited intrinsic regeneration capabilities of central nervous system (CNS) tissue following injury and disease. Of particular interest are systems that aid in oligodendrocyte regeneration, as oligodendrocytes generate myelin which surrounds neuronal axons and helps transmit signals throughout the CNS. Oligodendrocyte precursor cells (OPCs) are found in small numbers in the adult CNS, but are unable to effectively differentiate following CNS injury. Delivery of signaling molecules can initiate a favorable OPC response, such as proliferation or differentiation. Here, we investigate the delivery of one such molecule, platelet derived growth factor‐AA (PDGF‐AA), from poly(lactic‐co‐glycolic) acid microparticles to OPCs in a 3D polyethylene glycol‐based hydrogel. The goal of this DDS was to better understand the relationship between PDGF‐AA release kinetics and OPC fate. The system approximates native brain tissue stiffness, while incorporating PDGF‐AA under seven different delivery scenarios. Within this DDS, supply of PDGF‐AA followed by PDGF‐AA withdrawal caused OPCs to upregulate gene expression of myelin basic protein (MBP) by factors of 1.6–9.2, whereas continuous supply of PDGF‐AA caused OPCs to remain proliferative. At the protein expression level, we observed an upregulation in O1, a marker for mature oligodendrocytes. Together, these results show that burst release followed by withdrawal of PDGF‐AA from a hydrogel DDS stimulates survival, proliferation, and differentiation of OPCsin vitro. Our results could inform the development of improved neural regeneration strategies that incorporate delivery of PDGF‐AA to the injured CNS. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2402–2411, 2018.
Highly efficient extracellular expression of naturally cytoplasmic Leuconostoc mesenteroides sucrose phosphorylase
Authors: Su Lingqia , Wang Tian , Yu Lingang , Wu Jing
Published: April 2018

BACKGROUND

We previously showed that extracellular production of naturally cytoplasmic proteins could be realized through co‐expression with phospholipase C (PLC), which enhances cell membrane permeability through limited hydrolysis of membrane phospholipids. Leuconostoc mesenteroides sucrose phosphorylase (SPLc), a naturally cytoplasmic enzyme, exhibits excellent properties for synthesis of α‐arbutin, but no systemic investigation of its preparation has thus far been reported.

RESULTS

Three PLCs were selected and expressed, without signal peptide, in Escherichia coli. More than 90% of the PLCs from Listeria monocytogenes and Bacillus cereus were present in the culture medium. When SPLc was co‐expressed with these PLCs, and the location of the PLC and SPLc genes in the co‐expression vector was optimized, the highest production was obtained when SPLc gene was inserted upstream of the B. cereus PLC gene, as in BL21(DE3)/pETDuet‐sp‐bcplc. SPLc production was then scaled up to a 3 L fermenter and fermentation conditions were optimized. When the initial medium contained 0.6 mmol L−1 ZnCl2 and protein expression was induced at a dry cell weight of 15 g L−1 by the addition of lactose at 0.2 g L−1 h−1 at 30 °C, the extracellular SPLc activity reached its highest level of 1445.1 U mL−1 This constituted 81.6% of total activity; the remainder of the enzyme (18.4%) remained inside the cells.

CONCLUSION

This is the first report describing extracellular expression of sucrose phosphorylase, and the highest yield ever reported was obtained. This provides the basis for industrial‐scale production and application of sucrose phosphorylase. It also provides a potential method for improving the production of other proteins and fine chemicals. © 2018 Society of Chemical Industry
New Pyrazole‐ and Benzimidazole‐derived Ligand Systems
Authors: Nozari Mohammad , Addison Anthony W. , Reeves GorDan T. , Zeller Matthias , Jasinski Jerry P. , Kaur Manpreet , Gilbert Jayakumar G. , Hamilton Clifton R. , Popovitch Jonathan M. , Wolf Lawrence M. , Crist Lindsay E. , Bastida Natalia
Published: April 2018

A series of N‐containing heterocyclic compounds have been synthesized using approaches such as the well‐known Knorr synthesis, and a facile N‐alkylation method. This series of compounds includes pyrazole derivatives, tris(2‐benzimidazolylmethyl)amine derivatives, and “pincer” ligands. Characterization methods include 1H NMR, FT‐IR, CHN analyses, UV‐vis spectroscopy, and fluorimetry, while X‐ray crystal structures are reported for most of the compounds. The crystallographic results affirm a 13C NMR method for isomer assignment of substituted pyrazoles.
Design, Synthesis and In Vitro Antitubercular Evaluation of Isatin‐ciprofloxacin Hybrids with Hydrogen Bonding Capacity
Authors: Fan Yi‐Lei , Liu Min , Zhang Feng‐zhi , Zhang Shu
Published: April 2018

A series of novel isatin‐ciprofloxacin hybrids inhaling oxime, semicarbazone, and thiosemicarbazone groups with hydrogen bonding capacity were designed, synthesized, and evaluated for their in vitro antitubercular activities against Mycobacterium tuberculosis (MTB) H37Rv and multidrug‐resistant‐TB (MDR‐TB). All hybrids endowed with potential activities against the tested MTB H37Rv and MDR‐TB strains with minimum inhibitory concentration (MIC) in a range of 0.20 to 128 μg/mL. In particular, the most active hybrid 5e (MIC: 0.20 and 0.5 μg/mL) was four and two times more active than the parent ciprofloxacin (MIC: 0.78 μg/mL) and rifampicin (MIC: 0.39 μg/mL) against MTB H37Rv, and 4–>256 times more potent than the three references ciprofloxacin (MIC: 2.0 μg/mL), rifampicin (MIC: 32 μg/mL), and isoniazid (>128 μg/mL) against MDR‐TB. Thus, this kind of hybrids holds great promise as future anti‐TB agents against both drug‐sensitive and drug‐resistant MTB strains infection.
Rapid Synthesis of 2‐Alkanol‐substituted Pyrrolo[2,3‐b]quinoxalines from Propargylic Alcohols via Copper‐free Sonogashira Coupling Reaction at Room Temperature
Authors: Fakharian Mahsa , Keivanloo Ali , Nabid Mohammad Reza
Published: April 2018

A practical and efficient procedure is established for the synthesis of 2‐alkanol‐substituted pyrrolo[2,3‐b]quinoxalines by the reaction of N‐alkyl‐3‐chloroquinoxaline‐2‐amines with propargylic alcohols. The reaction is carried out in the absence of any copper salt but in the presence of a catalytic amount of Pd(PPh3)2Cl2 at room temperature. The Sonogashira coupling reaction step in this procedure is fast, producing clean products with high yields without contamination by unwanted homocoupling Glaser reaction products. The synthesized pyrroloquinoxaline derivatives are also screened against the three bacterial strains Micrococcus luteus, pseudomonas aeruginosa, and Bacillus subtilis.
Synthesis, Characterization, and Antimicrobial Screening of 4″‐methyl‐2,2″‐diaryl‐4,2′:4′,5″‐terthiazole Derivatives
Authors: Nalawade Jitendra , Mhaske Pravin C. , Shinde Abhijit , Patil Sachin V. , Choudhari Prafulla B. , Bobade Vivek D.
Published: April 2018

A series of novel 4″‐methyl‐2,2″‐diaryl‐4,2′:4′,5″‐terthiazole (8a‐p) derivatives has been synthesized and screened for antibacterial activity against four pathogenic bacteria, Escherichia coli, Pseudomonas flurescence, Staphylococcus aureus, and Bacillus subtilis. Among them, compounds 8a and 8j exhibited excellent antibacterial activity with minimum inhibitory concentration range of 1.0 to 5.3 μg/mL and compounds 8m and 8p exhibited moderate to good antibacterial activity with minimum inhibitory concentration range of 16.9 to 29.7 μg/mL against all tested strains. All the synthesized compounds were screened for their in vitro antifungal activity against Cocinida candida. Most of the compounds reported moderate antifungal activity. This study provides valuable directions to our ongoing endeavor of rationally designing more potent antimicrobial agent.
Synthesis and Antimicrobial Activities of Novel Quinazolinone Acylhydrazone Derivatives Containing the Indole Moiety
Authors: Li Xiao‐Qin , Gan Yi‐Yuan , Meng Jiao , Li Wen , Chen Jie , Qi Ya‐Yun , Tian Kun , Ouyang Gui‐Ping , Wang Zhen‐Chao
Published: April 2018

A series of novel quinazolinone acylhydrazone derivatives containing the indole moiety were designed, synthesized, and evaluated for their inhibition activities against some important phytopathogens in vitro. Antibacterial experiments indicated that some compounds exhibited remarkable inhibition activities against tested bacteria. Especially, the EC50 values of 7a (EC50 = 55.13 μg/mL against Xoo, EC50 = 56.92 μg/mL against Rs) demonstrated the best antibacterial activities against Xoo and Rs than the other compounds, and the control agents Bismerthiazol (EC50 = 89.80 μg/mL against Xoo) and Thiodiazole copper (EC50 = 189.52 μg/mL against Rs), moreover, compound 7o (EC50 = 50.80 μg/mL) displayed the excellent activity against Xac than the control Bismerthiazol (EC50 = 56.92 μg/mL).
Microreview: Pyrrol‐3‐yl squaraines (including indol‐3‐yl squaraines)
Authors: Lynch Daniel E. , Hamilton Darren G.
Published: April 2018

Pyrrol‐3‐yl squaraine dyes are prepared by the condensation of 3,4‐dihydroxycyclobut‐3‐ene‐1,2‐dione with two‐molar equivalence of a 2,5‐disubstituted pyrrole possessing a free β‐position, or substituted indoles with a similarly free β‐position. From the first reported syntheses of two indol‐3‐yl squaraines in 1966, numerous pyrrol‐3‐yl squaraines (including indol‐3‐yl squaraines) have been reported in both the scientific and patent literatures. This microreview highlights the synthesis, history, spectroscopy, and applications of pyrrol‐3‐yl squaraines from their first preparation to the present date.
Intermolecular interaction of fosinopril with bovine serum albumin (BSA): The multi‐spectroscopic and computational investigation
Authors: Zhou Kai‐Li , Pan Dong‐Qi , Lou Yan‐Yue , Shi Jie‐Hua
Published: April 2018

The intermolecular interaction of fosinopril, an angiotensin converting enzyme inhibitor with bovine serum albumin (BSA), has been investigated in physiological buffer (pH 7.4) by multi‐spectroscopic methods and molecular docking technique. The results obtained from fluorescence and UV absorption spectroscopy revealed that the fluorescence quenching mechanism of BSA induced by fosinopril was mediated by the combined dynamic and static quenching, and the static quenching was dominant in this system. The binding constant, Kb, value was found to lie between 2.69 × 103 and 9.55 × 103 M−1 at experimental temperatures (293, 298, 303, and 308 K), implying the low or intermediate binding affinity between fosinopril and BSA. Competitive binding experiments with site markers (phenylbutazone and diazepam) suggested that fosinopril preferentially bound to the site I in sub‐domain IIA on BSA, as evidenced by molecular docking analysis. The negative sign for enthalpy change (ΔH0) and entropy change (ΔS0) indicated that van der Waals force and hydrogen bonds played important roles in the fosinopril‐BSA interaction, and 8‐anilino‐1‐naphthalenesulfonate binding assay experiments offered evidence of the involvements of hydrophobic interactions. Moreover, spectroscopic results (synchronous fluorescence, 3‐dimensional fluorescence, and Fourier transform infrared spectroscopy) indicated a slight conformational change in BSA upon fosinopril interaction.
A sensitive, high‐throughput, and ecofriendly method for the determination of lumefantrine, artemether, and its active metabolite dihydroartemisinin by supercritical fluid chromatography and tandem mass spectrometry
Authors: Yang Yinxian , Gao Hailing , Hou Shanshan , Su Ruijuan , Liu Hongzhuo , Sun Jin
Published: April 2018

A quick and sensitive supercritical fluid chromatography with tandem mass spectrometry method for the simultaneous determination of lumefantrine, artemether, and its active metabolite dihydroartemisinin in rat plasma was developed and validated. The chromatographic separation was performed on an ACQUITY UPC2™ BEH 2‐EP column within 2.5 min by gradient elution using compressed CO2 and methanol containing 2 mM ammonium acetate as the mobile phases. Detection was achieved by multiple reaction monitoring using electrospray ionization in the positive ionization mode. For sample preparation, 50 μL of the sample was processed by modified high‐throughput, one‐step protein precipitation using hydrogen peroxide as a stabilizer to protect the endoperoxide‐containing artemisinin derivatives from degradation. The calibration curves were linear over the concentration range of 2.0–1000 ng/mL for both artemether and dihydroartemisinin, and 1.0–5000 ng/mL for lumefantrine. The values of selectivity, lower limit of quantification, linearity, accuracy, precision, matrix effects, stability, and recovery met the acceptable range according to the Food and Drug Administration guidelines. The developed method enables high resolution and speed as well as low cost, low solvent consumption, and short time and was successfully applied to pharmacokinetic studies through the intravenous administration of an artemether–lumefantrine lipid emulsion in rats.
Cyclic band compression in toroidal capillary electrophoresis delivers an unlimited number of theoretical plates with a quadratic growth in time and a constant peak capacity
Authors: Kist Tarso B. Ledur
Published: April 2018

Analytical instruments able to provide extremely high sensitivities, separation efficiencies, and peak capacities are important for both applied sciences and basic research. It is even more interesting if this can be achieved within organic, aqueous, and physiological solutions without restricting the operation parameters, such as buffer pH, temperature, ionic strength, and background electrolyte composition. Toroidal capillary electrophoresis offers this potential, as was recently proposed and demonstrated. In this platform, the analytes perform continuous round trips inside a fused‐silica capillary having a torus‐like shape. In the present work, the equations of the number of plates and peak capacity are deduced when on‐column cyclic thermal band compression is applied. They are expressed as a function of the number of turns performed by the analyte, axial length of the toroid, number of microholes (reservoirs), compression factor, number of compression events performed per turn, and applied voltage. It was found that the variances of the bands reach a steady state, regardless of the number of dispersion mechanisms present. Consequently, the number of theoretical plates grows indefinitely as the square of time. The expression of peak capacity shows a well‐defined limiting value that remains constant over time.
Malleostapedotomy in stapes revision surgery: Is an endoscopic approach possible?
Authors: Iannella Giannicola , Angeletti Diletta , Manno Alessandra , Pasquariello Benedetta , Re Massimo , Magliulo Giuseppe
Published: April 2018

Objectives/Hypothesis

The purpose of the present study was to show our preliminary results regarding the endoscopic ear surgery application in malleostapedotomy surgery.

Study Design

Case series.

Methods

Six patients (four females and two males) who underwent endoscopic ear surgery as revision surgery for otosclerosis were enrolled in this study. For endoscopic malleostapedotomy surgery, rigid angled endoscopes at 0 ° and 30 ° with a length of 14 cm and an outer diameter of 3 and 4 mm were used. A superelastic nitinol stapes prosthesis was used to connect the malleus neck to the oval window.

Results

During endoscopic ear surgery, a lateral ossicular chain fixation was present in all cases. The mean operative time in the study group was 81 minutes (range, 73–89 minutes). A statistically significant difference between preoperative and postoperative hearing findings was observed (P = .007). No cases of sensorineural hearing loss or persistent vertigo were observed in the study sample. No cases of prosthesis displacement or prosthesis extrusion occurred after a mean follow‐up of 11.5 months.

Conclusions

In 100% of treated cases, the endoscope proved to be adequate for the visualization of the malleus handle and incus, and of their possible abnormalities. Despite the difficulty related to endoscopic single‐handed work, none of the surgical steps of endoscopic malleostapedotomy were considered not feasible by endoscopic ear surgery.

Level of Evidence

4. Laryngoscope, 2611–2614, 2018
Survey of endoscopic skull base surgery practice patterns among otolaryngologists
Authors: Wannemuehler Todd J. , Rabbani Cyrus C. , Burgeson Jack E. , Illing Elisa A. , Walgama Evan S. , Wu Arthur W. , Ting Jonathan Y.
Published: April 2018

Background

Endoscopic skull base surgery (ESBS) is a rapidly expanding field. Despite divergent reported preferences for reconstructive techniques and perioperative management, limited data exist regarding contemporary practice patterns among otolaryngologists performing ESBS. This study aims to elucidate current practice patterns, primarily the volumes of cases performed and secondarily a variety of other perioperative preferences.

Methods

An anonymous 32‐item electronic survey examining perioperative ESBS preferences was distributed to the American Rhinologic Society membership. Statistical significance between variables was determined utilizing Student t, chi‐square, and Fisher exact tests.

Results

Seventy otolaryngologists completed the survey. The effective response rate was approximately 22.5%. Sixty percent of respondents were in full‐time academic practice and 70% had completed rhinology/skull base fellowships. Annually, 43.3 mean ESBS cases were performed (29.1 private practice vs. 52.9 academic practice, P = .009). Academic practice averaged 24.1 expanded cases versus only 11 in private practice (P = .01). Of respondents, 55.7% stood on the same side as the neurosurgeon and 72.9% remained present for the entire case. Current procedural terminology coding and antibiotic regimens were widely divergent; 31.4% never placed lumbar drains preoperatively, while 41.4% did so for anticipated high‐flow cerebrospinal fluid leaks. While considerable variation in reconstructive techniques were noted, intradural defect repairs utilized vascularized flaps 86.3% of the time versus only 51.3% for extradural repairs (P < 0.001). Major complications were rare. Postoperative restrictions varied considerably, with most activity limitations between 2–8 weeks and positive airway pressure use for 2–6 weeks. Most respondents started saline irrigations 0–2 weeks postoperatively.

Conclusions

Based on responses from fellowship‐ and non‐fellowship‐trained otolaryngologists in various practice settings, there remains considerable variation in the perioperative management of patients undergoing ESBS.

Level of Evidence

5
Therapeutic Cannabis and Endocannabinoid Signaling System Modulator Use in Otolaryngology Patients
Authors: Bryant Lucas M. , Daniels Kelly E. , Cognetti David M. , Tassone Patrick , Luginbuhl Adam J. , Curry Joseph M.
Published: April 2018

Objectives

1) review benefits and risks of cannabis use, with emphasis on otolaryngic disease processes; 2) define and review the endocannabinoid signaling system (ESS); and 3) review state and federal regulations for the use and research of cannabis and ESS modulators.

Methods

This manuscript is a review of the current literature relevant to the stated objectives.

Results

Cannabis (marijuana) use is increasing. It is the most widely used illicit substance in the world. There is increasing interest in its therapeutic potential due to changing perceptions, new research, and legislation changes controlling its use. The legal classification of cannabis is complicated due to varied and conflicting state and federal laws. There are currently two synthetic cannabinoid drugs that are FDA approved. Current indications for use include chemotherapy‐related nausea and vomiting, cachexia, and appetite loss. Research has demonstrated potential benefit for use in many other pathologies including pain, inflammatory states, and malignancy. Data exists demonstrating potential antineoplastic benefit in oral, thyroid, and skin cancers.

Conclusions

ESS modulators may play both a causal and therapeutic role in several disorders seen in otolaryngology patients. The use of cannabis and cannabinoids is not without risk. There is a need for further research to better understand both the adverse and therapeutic effects of cannabis use. With increasing rates of consumption, elevated public awareness, and rapidly changing legislation, it is helpful for the otolaryngologist to be aware of both the adverse manifestations of use and the potential therapeutic benefits when talking with patients.