bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective spectrofluorimetric method for determination of Lisinopril in pharmaceutical preparations and in presence of hydrochlorothiazide: Application to content uniformity testing
Authors: Derayea Sayed M. , Badr El‐Din Khalid M. , Mohammed Fatma F.
Published: July 2017

A novel sensitive and cost‐effective spectrofluorimetric method has been developed and validated for determination of lisinopril (an angiotensin converting enzyme inhibitor) in its pure form and pharmaceutical preparations. The method is based on the reaction of the drug with ninhydrin and phenylacetaldehyde in buffered medium (pH 7.0) to form a highly fluorescent product measured at 460 nm after excitation at 390 nm. Different experimental parameters were optimized and calibration curve was constructed. The fluorescence‐concentration relationship was linear in the range of 0.15–4.0 μg mL−1. The calculated Limit of detection (LOD) and Limit of quantitation (LOQ) were 0.04 and 0.12 μg mL−1, respectively. The method was successfully applied for the analysis of pharmaceutical preparations containing the studied drug either alone or co‐formulated with hydrochlorothiazide. The obtained results were in agreement with those of the reported method in respect to accuracy and precession. Moreover, the method was applied content uniformity testing according to United States Pharmacopeia (USP) guidelines.
Creating 3D physical models to probe student understanding of macromolecular structure
Authors: Cooper A. Kat , Oliver‐Hoyo M. T.
Published: July 2017

The high degree of complexity of macromolecular structure is extremely difficult for students to process. Students struggle to translate the simplified two‐dimensional representations commonly used in biochemistry instruction to three‐dimensional aspects crucial in understanding structure–property relationships. We designed four different physical models to address student understanding of electrostatics and noncovalent interactions and their relationship to macromolecular structure. In this study, we have tested these models in classroom settings to determine if these models are effective in engaging students at an appropriate level of difficulty and focusing student attention on the principles of electrostatic attractions. This article describes how to create these unique models for four targeted areas related to macromolecular structure: protein secondary structure, protein tertiary structure, membrane protein solubility, and DNA structure. We also provide evidence that merits their use in classroom settings based on the analysis of assembled models and a behavioral assessment of students enrolled in an introductory biochemistry course. By providing students with three‐dimensional models that can be physically manipulated, barriers to understanding representations of these complex structures can be lowered and the focus shifted to addressing the foundational concepts behind these properties. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(6):491–500, 2017.
Fabrication of Hollow Mesoporous Nanosized ZSM‐5 Catalyst with Superior Methanol‐to‐Hydrocarbons Performance by Controllable Desilication
Authors: Fu Tingjun , Qi Ruiyue , Wan Weili , Shao Juan , Wen John Z. , Li Zhong
Published: July 2017

This work aims to improve the catalyst lifetime of ZSM‐5 for the methanol‐to‐hydrocarbons conversion by tuning the pore structure and external surface area on nano‐ZSM‐5 (100 nm). Several differently pore‐structured samples were synthesized based on the controllable desilication of nano‐ZSM‐5 by prolonging the alkali‐treatment time and introducing tetrapropylammonium hydroxide (TPAOH) into NaOH solution. 2 h NaOH treatment produced mesoporous ZSM‐5 with well‐maintained interior, and the catalytic lifetime was prolonged from 60 to 127 h along with increased isoparaffins selectivity owing to improved diffusion and accessibility of internal weak acid sites. If prolonging the treating time to 15 h, nano‐ZSM‐5 with initially formed hollow structure (HI‐Z5) was achieved, which shows relatively short lifetime of 85 h and high aromatics selectivity. After a secondary treatment of HI‐Z5 with fresh NaOH solution for 5 h, the formed thin shell and clean interior significantly improved diffusion, and the lifetime increased from 85 to 115 h. The aromatics selectivity was also increased by the enhanced acidity. Mesopores were introduced into the shell of HI‐Z5 after treating it with a freshly mixed solution of NaOH and TPAOH. The external surface area exhibited a 94 % increase, resulting in a high isoparaffins selectivity and a long lifetime of 149 h.
Nano‐confined Mo2C Particles Embedded in a Porous Carbon Matrix: A Promising Anode for Ultra‐stable Na Storage
Authors: Liao Hanxiao , Hou Hongshuai , Zhang Yan , Qiu Xiaoqing , Ji Xiaobo
Published: July 2017

Transition‐metal carbides (TMCs) are emerging as promising electrode materials for electrochemical energy storage devices, owing to their good conductivity and stability. Herein, Mo2C nanoparticles have been successfully encapsulated into a porous N‐doped carbon matrix through in situ confined carbonization. When evaluated as an anode material for sodium‐ion batteries (SIBs), the resultant Mo2C/N‐doped composite (Mo2C‐NC) exhibited a high rate capability and excellent cycle stability with a high capacity retention of 95.4 % after 2500 cycles. The prominent sodium storage performances can be attributed to its special nanoarchitecture, which provides a synergistic effect to offer shortened Na+/e− transfer pathways, highly effective restraint through particle agglomeration, and a buffer for the drastic volume change during the prolonged cycles. Owing to the efficient one‐pot procedure and high electrochemical performances, the porous Mo2C/N‐doped carbon hybrids are great potential anode materials for rechargeable SIBs.
Cyclopropyl Group: An Excited‐State Aromaticity Indicator?
Authors: Ayub Rabia , Papadakis Raffaello , Jorner Kjell , Zietz Burkhard , Ottosson Henrik
Published: July 2017

The cyclopropyl (cPr) group, which is a well‐known probe for detecting radical character at atoms to which it is connected, is tested as an indicator for aromaticity in the first ππ* triplet and singlet excited states (T1 and S1). Baird's rule says that the π‐electron counts for aromaticity and antiaromaticity in the T1 and S1 states are opposite to Hückel's rule in the ground state (S0). Our hypothesis is that the cPr group, as a result of Baird's rule, will remain closed when attached to an excited‐state aromatic ring, enabling it to be used as an indicator to distinguish excited‐state aromatic rings from excited‐state antiaromatic and nonaromatic rings. Quantum chemical calculations and photoreactivity experiments support our hypothesis; calculated aromaticity indices reveal that openings of cPr substituents on [4n]annulenes ruin the excited‐state aromaticity in energetically unfavorable processes. Yet, polycyclic compounds influenced by excited‐state aromaticity (e.g., biphenylene), as well as 4nπ‐electron heterocycles with two or more heteroatoms represent limitations.
Modified Bruggeman models for prediction of CO2 permeance in polycarbonate/silica nanocomposite membranes
Authors: Idris Alamin , Man Zakaria , Maulud Abdulhalim Shah , Uddin Fahim
Published: July 2017

The polycarbonate membranes performances are improved by the incorporation of silica nanoparticles into the polymer matrix. Prepared PC/silica nanocomposite membranes with various silica content are considered and the experimental relative permeance of CO2 gas at 200 kPa (2 bar) feed pressure are used as reference in the predictions using the existing theoretical models such as Maxwell‐Wagner‐Sillar, Bruggeman, Lewis‐Nielsen, Pal, and modified Pal models. TEM and BET analysis were used to characterize the silica nanoparticles; FESEM was used to characterize the morphology of the nanocomposite membranes. The TEM image of the silica nanoparticles reveals that the nanoparticles are mostly spherical. BET results reveal that the surface area and pore diameter of the silica nanoparticles are 618.8 m2/g and 0.28 nm, respectively. The existing models have resulted in poor predictions with errors AARE % of 26.52 to 28.02 %. Observation by FESEM image shows that the dispersed particles are surrounded by interfacial voids and rigidified polymer layer. Modified Bruggeman models that consider the interfacial volume show appreciable prediction with AARE 4.59 % being obtained with the pseudo‐two‐phase Bruggeman model. Moreover, when the model considered pseudo‐three‐phase morphology, the AARE % value reduced to 3.92 %. Thus, the contribution due to the interfacial rigidified layer was minimal.
Welche Vorstellungen, Interessen und Selbstwirksamkeitserwartungen zu naturwissenschaftlichen Tätigkeiten weisen Studierende der Naturwissenschaften auf?
Authors: Wentorf Wilfried , Höffler Tim N. , Parchmann Ilka
Published: July 2017

Die Vorstellungen Jugendlicher über konkrete naturwissenschaftliche Tätigkeitsfelder und ihre eigenen diesbezüglichen Interessen und Einstellungen werden geprägt durch den naturwissenschaftlichen Unterricht und die Fachlehrerinnen und ‐lehrer als Multiplikatoren und Repräsentanten dieser Domäne. Vorgestellt wird eine Studie, in der an fünf Universitätsstandorten Lehramtsstudierende und Fachstudierende zu Beginn ihres Studiums nach ihren eigenen Vorstellungen, Interessen und Selbstwirksamkeitserwartungen bezüglich konkreter naturwissenschaftlicher Tätigkeiten befragt wurden (N=563). Auf Basis dieser Konzepte über Naturwissenschaften wird diskutiert, welche Chancen und Schwierigkeiten sich für die das transportiert Bild heutiger Naturwissenschaften ergeben könnten.
Biodegradation and Co‐Metabolism of Monochlorophenols and 2,4‐Dichlorophenol by Microbial Consortium
Authors: Patel Bhishma P. , Kumar Arvind
Published: July 2017

In the present study, biodegradation of monochlorophenols (MCPs) and their co‐metabolism with 2,4‐dichlorophenol (2,4‐DCP) using mixed microbial consortium has been reported. The mixed consortium has shown 44 to 100% degradation of 50 to 300 mg L–1 3‐chlorophenol (3‐CP). While in case of 4‐CP, the degradation observed was 46 to 100% of 100 to 600 mg L−1 of initial concentrations. HPLC and spectrophotometric analysis indicated that the degradation occurred via a meta‐cleavage pathway. 4‐Chlorocatechol was observed as a common intermediate for both 3‐CP and 4‐CP degradation pathways. The transformation of 4‐chlorocatechol to maleylacetate via 5‐chloro 2‐hydroxymuconic semialdehyde indicated the complete degradation of both 3‐CP and 4‐CP. The co‐metabolic study of 2,4‐DCP in the presence of MCPs showed that the degradation of 2,4‐DCP increases in the presence of 3‐CP and 4‐CP. The biodegradation (mg L−1 per day) in the quaternary mixture of MCPs and DCP occurred in the order of 3‐CP > 4‐CP > DCP > 2‐CP. The biodegradation kinetics constants obtained for 3‐CP were Rm = 1.96 mg L−1 h−1, Ks = 47.23 mg L−1, Ki = 104.12 mg L−1, and for 4‐CP were Rm = 6.33 mg L−1 h−1, Ks = 1262 mg L−1, Ki = 1408.8 mg L−1 by Andrew's substrate inhibition model using MATLAB 6.5.
Keeping the focus on biophysics and actin filaments in Nagoya: A report of the 2016 “now in actin” symposium
Authors: Fujiwara Ikuko , Narita Akihiro
Published: July 2017

Regulatory systems in living cells are highly organized, enabling cells to response to various changes in their environments. Actin polymerization and depolymerization are crucial to establish cytoskeletal networks to maintain muscle contraction, cell motility, cell division, adhesion, organism development and more. To share and promote the biophysical understanding of such mechanisms in living creatures, the “Now in Actin Study: ‐Motor protein research reaching a new stage‐” symposium was organized at Nagoya University, Japan on 12 and 13, December 2016. The organizers invited emeritus professor of Nagoya and Osaka Universities Fumio Oosawa and leading scientists worldwide as keynote speakers, in addition to poster presentations on cell motility studies by many researchers. Studies employing various biophysical, biochemical, cell and molecular biological and mathematical approaches provided the latest understanding of mechanisms of cell motility functions driven by actin, microtubules, actin‐binding proteins, and other motor proteins.
Behavioral and stereological characterization of Hdc KO mice: Relation to Tourette syndrome
Authors: Abdurakhmanova Shamsiiat , Chary Karthik , Kettunen Mikko , Sierra Alejandra , Panula Pertti
Published: July 2017

A premature termination codon in the human histidine decarboxylase (Hdc) gene has been identified in a family suffering from Guilles de la Tourette syndrome (GTS). In the current study we investigated if mice lacking the histamine producing enzyme HDC share the morphological and cytological phenotype with GTS patients by using magnetic resonance (MRI) and diffusion tensor imaging (DTI), unbiased stereology and immunohistochemistry. Behavior of Hdc knock‐out (Hdc KO) mice was assessed in an open field test. The results of stereological, volumetric and DTI analysis measurements showed no significant differences between control and Hdc KO mice. The numbers and distribution of GABAergic parvalbumin or nitric oxide‐expressing and cholinergic interneurons were normal in Hdc KO mice. Cortical morphology and layering in adult Hdc KO mice were also preserved. In open field test Hdc KO mice showed impaired exploratory activity and habituation when introduced to novel environment. Our results indicate that Hdc deficiency in mice does not disturb the development of striatal and cortical interneurons and does not lead to the morphological and cytological phenotypes characterized by humans with GTS. Nevertheless, histamine deficiency leads to behavioral alterations probably due to neurotransmitter dysbalance on the level of the striatum.
Photochemical Water Splitting by Bismuth Chalcogenide Topological Insulators
Authors: Rajamathi Catherine R. , Gupta Uttam , Pal Koushik , Kumar Nitesh , Yang Hao , Sun Yan , Shekhar Chandra , Yan Binghai , Parkin Stuart , Waghmare Umesh V. , Felser Claudia , Rao C. N. R.
Published: July 2017

As one of the major areas of interest in catalysis revolves around 2D materials based on molybdenum sulfide, we have examined the catalytic properties of bismuth selenides and tellurides, which are among the first chalcogenides to be proven as topological insulators (TIs). We find significant photochemical H2 evolution activity with these TIs as catalysts. H2 evolution increases drastically in nanosheets of Bi2Te3 compared to single crystals. First‐principles calculations show that due to the topology, surface states participate and promote the hydrogen evolution.
Prospective Symbiosis of Green Chemistry and Energetic Materials
Authors: Kuchurov Ilya V. , Zharkov Mikhail N. , Fershtat Leonid L. , Makhova Nina N. , Zlotin Sergey G.
Published: July 2017

A global increase in environmental pollution demands the development of new “cleaner” chemical processes. Among urgent improvements, the replacement of traditional hydrocarbon‐derived toxic organic solvents with neoteric solvents less harmful for the environment is one of the most vital issues. As a result of the favorable combination of their unique properties, ionic liquids (ILs), dense gases, and supercritical fluids (SCFs) have gained considerable attention as suitable green chemistry media for the preparation and modification of important chemical compounds and materials. In particular, they have a significant potential in a specific and very important area of research associated with the manufacture and processing of high‐energy materials (HEMs). These large‐scale manufacturing processes, in which hazardous chemicals and extreme conditions are used, produce a huge amount of hard‐to‐dispose‐of waste. Furthermore, they are risky to staff, and any improvements that would reduce the fire and explosion risks of the corresponding processes are highly desirable. In this Review, useful applications of almost nonflammable ILs, dense gases, and SCFs (first of all, CO2) for nitration and other reactions used for manufacturing HEMs are considered. Recent advances in the field of energetic (oxygen‐balanced and hypergolic) ILs are summarized. Significant attention is paid to the SCF‐based micronization techniques, which improve the energetic performance of HEMs through an efficient control of the morphology and particle size distribution of the HEM fine particles, and to useful applications of SCFs in HEM processing that makes them less hazardous.
Monomorphic epitheliotropic intestinal T‐cell lymphoma in pleural effusion: A case report
Authors: Antoniadou F. , Dimitrakopoulou A. , Voutsinas P. M. , Vrettou K. , Vlahadami I. , Voulgarelis M. , Korkolopoulou P. , Kafasi N. , Mikou P.
Published: July 2017

Dissemination of lymphomas in serous effusions is quite common. Cytology aims to contribute in the clinical management of haematologic patients, providing an accurate and rapid diagnosis. Ancillary techniques such as immunocytochemistry and flow cytometry are essential to classify the lymphoma entity. Comprehensive awareness of the clinical picture and previous histologic documentation are essential for a lymphomatous effusion diagnosis. We report an unusual case of monomorphic epitheliotropic intestinal T‐cell lymphoma, formerly known as enteropathy associated T‐cell lymphoma (EATL) type II, spreading in the pleural cavity. Cell morphology and immunohistochemistry of the pleural fluid were consistent with the histology of a jejunal tumor previously excised. Flow cytometry data were consistent, though not pathognomonic for the disease. Serous effusions with evidence of lymphoma involvement should be thoroughly examined with cytology and adjuvant techniques to provide diagnosis for proper therapeutic strategies.
Natural succession on abandoned cropland effectively decreases the soil erodibility and improves the fungal diversity
Authors: Zhang Chao , Liu Guobin , Song Zilin , Qu Dong , Fang Linchuan , Deng Lei
Published: July 2017

Changes in plants and soils during natural succession have been evaluated, but little is known about the effects of succession on the activities of soil microbes and their interactions with soil erodibility. We conducted a field study on the Chinese Loess Plateau, typical of this semiarid area, to determine the effect of secondary succession on the stability of soil structure against erosion and on the composition of soil fungal communities. Characteristics of plant, soil, and fungal communities were assessed across a 30‐yr chronosequence of grassland developed from abandoned cropland. The diversity and composition of the fungal communities were determined using high‐throughput sequencing of the internal transcribed spacer. Six grasslands were selected to represent different successional age classes: 0 (cropland), 5, 10, 15, 20, and 30 yr. Short‐term decreases (initial 5 yr) in the amounts of soil organic carbon, total nitrogen, available phosphorus, and fungal biomass and in fungal diversity had returned to original levels (i.e., cropland) within 15 yr and were much higher after continued succession. Abandoning cropland for succession caused the soil erodibility (K) decrease and the aboveground coverage, soil nutrient levels, content of larger (>5 mm) water‐stable aggregate, mean aggregate weight diameter, and diversity of the fungal communities improvement including arbuscular mycorrhizas (AMF), ectomycorrhizas (EMF), and saprotrophs. The fungal communities were dominated by Ascomycota, Zygomycota, Basidiomycota, and Glomeromycota during the succession. The successional patterns of the plant and fungal communities were similar, although distinct fungal communities were not observed in the two initial stages, suggesting that fungal succession may develop more slowly than plant succession. Plant root biomass, EMF, and soil organic carbon content accounted for most of the variation of soil erodibility (28.6%, 19.5%, and 11.8%, respectively), indicating their importance in shaping soil structure to prevent erosion. Our results demonstrated that abandoning cropland for natural succession could decrease soil erodibility and increase fungal diversity. EMF plays an important role in soil stability against erosion in the Loess Plateau. Abandoning cropland for natural succession should be recommended for alleviating soil erosion and improving the degraded soils in this area.
Chromatographic HPV‐16 E6/E7 plasmid vaccine purification employing L‐histidine and 1‐benzyl‐L‐histidine affinity ligands
Authors: Amorim Lúcia F. A. , Gaspar Rita , Pereira Patrícia , Černigoj Urh , Sousa Fani , Queiroz João António , Sousa Ângela
Published: July 2017

Affinity chromatography based on amino acids as interacting ligands was already indicated as an alternative compared to ion exchange or hydrophobic interaction for plasmid DNA purification. Understanding the recognition mechanisms occurring between histidine‐based ligands and nucleic acids enables more efficient purification of a DNA vaccine, as the binding and elution conditions can be adjusted in order to enhance the purification performance. Decreasing pH to slightly acidic conditions increases the positive charge of histidine ligand, what influences the type of interaction between chromatographic support and analytes. This was proven in this work, where hydrophobic effects established in the presence of ammonium sulfate were affected at pH 5.0 in comparison to pH 8.0, while electrostatic and cation‐π interactions were intensified. Histidine ligand at pH 5.0 interacts with phosphate groups or aromatic rings of plasmid DNA. Due to different responses of RNA and pDNA on mobile phase changes, the elution order between RNA and pDNA was changed with mobile phase pH decrease from 8.0 to 5.0. The phenomenon was more evident with L‐histidine ligand due to more hydrophilic character, leading to an improved selectivity of L‐histidine‐modified chromatographic monolith, allowing the product recovery with 99% of purity (RNA removal). With the 1‐benzyl‐ L‐histidine ligand, stronger and less selective interactions with the nucleic acids were observed due to the additional hydrophobicity associated with the phenyl aromatic ring. Optimization of sample displacement chromatography parameters (especially (NH4)2SO4 concentration) at slightly acidic pH enabled excellent isolation of pDNA, by the removal of RNA in a negative mode, with binding capacities above 1.5 mg pDNA per mL of chromatographic support.
Supramolecular gel electrophoresis of large DNA fragments
Authors: Tazawa Shohei , Kobayashi Kazuhiro , Oyoshi Takanori , Yamanaka Masamichi
Published: July 2017

Pulsed‐field gel electrophoresis is a frequent technique used to separate exceptionally large DNA fragments. In a typical continuous field electrophoresis, it is challenging to separate DNA fragments larger than 20 kbp because they migrate at a comparable rate. To overcome this challenge, it is necessary to develop a novel matrix for the electrophoresis. Here, we describe the electrophoresis of large DNA fragments up to 166 kbp using a supramolecular gel matrix and a typical continuous field electrophoresis system. C3‐symmetric tris‐urea self‐assembled into a supramolecular hydrogel in tris‐boric acid‐EDTA buffer, a typical buffer for DNA electrophoresis, and the supramolecular hydrogel was used as a matrix for electrophoresis to separate large DNA fragments. Three types of DNA marker, the λ‐Hind III digest (2 to 23 kbp), Lambda DNA‐Mono Cut Mix (10 to 49 kbp), and Marker 7 GT (10 to 165 kbp), were analyzed in this study. Large DNA fragments of greater than 100 kbp showed distinct mobility using a typical continuous field electrophoresis system.
Exposure effects of levonorgestrel on oogenesis in the fathead minnow (Pimephales promelas)
Authors: Frankel Tyler , Yonkos Lance , Frankel Jack
Published: July 2017

The synthetic progestin levonorgestrel is commonly utilized in human oral contraceptives. It enters the environment as a component of wastewater treatment plant effluent, and has been measured at low ng/L concentrations in surface waters. It has been shown to activate fish androgen receptors, causing the physical masculinization of females, changes in reproductive behavior, and decreases in fecundity. In the present study, the effects of levonorgestrel exposure on early-stage oogenesis in the fathead minnow (Pimephales promelas) was examined. Adult females were exposed to 0, 10, or 100 ng/L levonorgestrel for 14 d using a flow-through exposure system. The ovaries from each female were then removed via dissection and weighed for gonadosomatic index (GSI) calculations, and oocytes from one lobe preserved in Serra's fixative. Total numbers of late-stage vitellogenic oocytes exhibiting a germinal vesicle were then quantified. In a second exposure, blood plasma samples were collected from adult females and analyzed for vitellogenin concentrations using enzyme-linked immunosorbent assay. Females exposed to both concentrations of levonorgestrel developed male secondary sexual characteristics in a dose-dependent manner, and ovaries contained significantly fewer late stage oocytes. Exposure to 100 ng/L of levonorgestrel resulted in decreased GSI and blood plasma vitellogenin concentrations. The results suggest that female exposure to levonorgestrel alone may have profound effects on reproduction in progestin-contaminated environments. Environ Toxicol Chem 2017;36:3299–3304. © 2017 SETAC
Hospital volume and mortality after transjugular intrahepatic portosystemic shunt creation in the United States
Authors: Sarwar Ammar , Zhou Lujia , Novack Victor , Tapper Elliot B. , Curry Michael , Malik Raza , Ahmed Muneeb
Published: July 2017

The link between higher procedure volume and better outcomes for surgical procedures is well established. We aimed to determine whether procedure volume affected inpatient mortality in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS). An epidemiological analysis of an all‐payer database recording hospitalizations during 2013 in the United States (Nationwide Readmissions Database) was performed. All patients ≥ 18 years old undergoing TIPS during a hospital admission (n = 5529) without concurrent or prior liver transplantation were selected. All‐cause inpatient mortality was assessed. Risk‐adjusted mortality was assessed for hospitals categorized into quintiles based on annual TIPS volume (very low, 1‐4/year; low, 5‐9/year; medium, 10‐19/year; high, 20‐29/year; and very high, ≥ 30/year). TIPS were placed in all 5529 patients (mean age, 57 years [standard deviation, ± 10.9 years]; women, n = 2071; men, n = 3458). Mortality decreased with rising annual TIPS volume (13% for very low to 6% for very high volume hospitals; P < 0.01). Elective admissions were more common in hospitals with higher annual TIPS volume (20.3% for very low to 30.8% for very high; P < 0.01). On multivariate analysis, compared with hospitals performing ≥30 TIPS per year, only hospitals performing 1‐4/year (adjusted odds ratio [aOR], 1.9; 95% confidence interval [CI], 1.21‐3.01; P = 0.01), 5‐9/year (aOR, 2.0; 95% CI, 1.25‐3.17; P < 0.01), and 10‐19/year (aOR, 1.9; 95% CI, 1.17‐3.00; P = 0.01) had higher inpatient mortality (20‐29/year: aOR, 1.4; 95% CI, 0.84‐2.84; P = 0.19). The absolute difference between risk‐adjusted mortality rate for very low volume and very high volume hospitals was 6.1% (13.9% versus 7.8%). TIPS volume of ≤ 20 TIPS/year, variceal bleeding, and nosocomial infections were independent risk factors for inpatient mortality in patients with both elective and emergent admissions. Conclusion: The risk of inpatient mortality is lower in hospitals performing ≥20 TIPS per year. Future research exploring preventable factors for higher mortality and benefits of patient transfer to higher volume centers is warranted. (Hepatology 2018;67:690‐699).
Gene cloning, characterization, and cytotoxic activity of methionine γ‐lyase from Clostridium novyi
Authors: Kulikova Vitalia V. , Morozova Elena A. , Revtovich Svetlana V. , Kotlov Mikhail I. , Anufrieva Natalya V. , Bazhulina Natalya P. , Raboni Samanta , Faggiano Serena , Gabellieri Edi , Cioni Patrizia , Belyi Yury F. , Mozzarelli Andrea , Demidkina Tatyana V.
Published: July 2017

The exploitation of methionine‐depleting enzyme methionine γ‐lyase (MGL) is a promising strategy against specific cancer cells that are strongly dependent on methionine. To identify MGL from different sources with high catalytic activity and efficient anticancer action, we have expressed and characterized MGL from Clostridium novyi and compared its catalytic efficiency with the previously studied MGL from Citrobacter freundii. The purified recombinant MGL exhibits kcat and kcat/Km for methionine γ‐elimination reaction that are 2.4‐ and 1.36‐fold higher than C. freundii enzyme, respectively, whereas absorption, fluorescence, and circular dichroism spectra are very similar, as expected on the basis of 87% sequence identity and high conservation of active site residues. The reactivity of cysteine residues with DTNB and iodoacetamide was investigated as well as the impact of their chemical modification on catalytic activity. This information is relevant because for increasing bioavailability and reducing immunogenity, MGL should be decorated with polyethylene glycol (PEG). It was found that Cys118 is a faster reacting residue, which results in a significant decrease in the γ‐elimination activity. Thus, the protection of Cys118 before conjugation with cysteine‐reacting PEG represents a valuable strategy to preserve MGL activity. The anticancer action of C. novyi MGL, evaluated in vitro against prostate (PC‐3), chronic myelogenous leucemia (K562), and breast (MDA‐MB‐231 and MCF7) cancer cells, exhibits IC50 of 1.3 U mL−1, 4.4 U mL−1, 1.2 U mL−1, and 3.4 U mL−1, respectively. A higher cytotoxicity of C. novyi MGL was found against cancer cells with respect to C. freundii MGL, with the exception of PC‐3, where a lower cytotoxicity was observed. © 2017 IUBMB Life, 69(9):668–676, 2017
BRD4 promotes gastric cancer progression through the transcriptional and epigenetic regulation of c‐MYC
Authors: Ba Mingchen , Long Hui , Yan Zhaofei , Wang Shuai , Wu Yinbing , Tu Yinuo , Gong Yuanfeng , Cui Shuzhong
Published: July 2017

Although the significance of BRD4 in the epigenetic memory and cancer genesis has been intensively investigated, little is known about its function and potential roles during the generation and progression of gastric cancer. We report here that BRD4 increases the proliferation and represses the apoptosis of gastric cancer cells through activating c‐MYC via transcriptional and epigenetic regulation mechanisms. Expression analyses in both small and large cohort of sample show that BRD4 is highly expressed in gastric cancer tissues/cells when compared with the adjacent non‐tumor tissues/normal cells. We also find a positive correlation between the expression of BRD4 and c‐MYC in patient samples. The repression of BRD4 by siRNAs leads to the down‐regulation of c‐MYC in gastric cancer cells. Chromatin immunoprecipitation‐qPCR and luciferase assays show that BRD4 binds to and coordinately activates c‐MYC promoter, indicating that c‐MYC is transcriptional target of BRD4 and BRD4 regulates its basal expression. Further evidence show that the histone acetylation inhibitor reduces the binding of BRD4 as well as the histone activation level on c‐MYC promoter, and leads to the down‐regulation of c‐MYC, suggesting that BRD4 regulates the expression of c‐MYC through epigenetic mechanism. Functionally, the suppression of BRD4 leads to growth inhibition and apoptosis in gastric cancer cells. Force expression of c‐MYC alongside with BRD4 repression rescue the anti‐cancer effects caused by BRD4 repression. Collectively, our data not only uncovered the mechanism of BRD4 in regulating the proliferation of gastric cancer cells but also provides a new therapeutic strategy for this type of cancer.
3,4‐dihydroxybenzalacetone and caffeic acid phenethyl ester induce preconditioning ER stress and autophagy in SH‐SY5Y cells
Authors: Tomiyama Ryoichi , Takakura Ken , Takatou Shouhei , Le Thuong M. , Nishiuchi Takumi , Nakamura Yutaka , Konishi Tetsuya , Matsugo Seiichi , Hori Osamu
Published: July 2017

3,4‐dihydroxybenzalacetone (DBL) and Caffeic acid phenethyl ester (CAPE) are both catechol‐containing phenylpropanoid derivatives with diverse bioactivities. In the present study, we analyzed the ability of these compounds to activate the unfolded protein response (UPR) and the oxidative stress response. When human SH‐SY5Y neuroblastoma cells were treated with DBL or CAPE, the expression of endoplasmic reticulum (ER) stress‐related genes such as HSPA5, HYOU1, DDIT3, and SEC61b increased to a larger extent in response to CAPE treatment, while that of antioxidant genes such as HMOX1, GCLM, and NQO1 increased to a larger extent in response to DBL treatment. DNA microarray analysis confirmed the strong link of these compounds to ER stress. Regarding the mechanism, activation of the UPR by these compounds was associated with enhanced levels of oxidized proteins in the ER, and N‐acetyl cysteine (NAC), which provides anti‐oxidative effects, suppressed the induction of the UPR‐target genes. Furthermore, both compounds enhanced the expression of LC3‐II, a marker of autophagy, and 4‐Phenylbutyric acid (4‐PBA), a chemical chaperone that reduces ER stress, suppressed it. Finally, pretreatment of cells with DBL, CAPE or low doses of ER stressors protected cells against a neurotoxin 6‐hydroxydopamine (6‐OHDA) in an autophagy‐dependent manner. These results suggest that DBL and CAPE induce oxidized protein‐mediated ER stress and autophagy that may have a preconditioning effect in SH‐SY5Y cells.
17β‐estradiol rescues damages following traumatic brain injury from molecule to behavior in mice
Authors: Lu Huaihai , Ma Kun , Jin Liwei , Zhu He , Cao Ruiqi
Published: July 2017

Traumatic brain injury (TBI) is a public health concern, and causes cognitive dysfunction, emotional disorders, and neurodegeration, as well. The currently available treatments are all symptom‐oriented with unsatifying efficacy. It is highly demanded to understand its underlying mechanisms. Controlled cortical impact (CCI) was used to induce TBI in aged female mice subjected to ovariectomy. Brain damages were assessed with neurological severity score, brain infarction and edema. Morris water maze and elevated plus maze were applied to evaluate the levels of anxiety. Apoptosis in the hippocampus was assayed with Fluoro‐Jade B staining and TUNEL staining. Western blot was employed to measure the expression of NMDA receptor subunits and phosphorylation of ERK1/2, and biochemical assays were used to estimate oxidative stress. 17beta‐Estradiol (E2) was intraperitoneally administered at 10–80 μg/kg once per day for 7 consecutive days before or after CCI. Chronic administration of E2 both before and immediately after CCI conferred neuroprotection, reducing neurological severity score, brain infarction, and edema in TBI mice. Additionally, E2 improved many aspects of deleterious effects of TBI on the hippocampus, including neuronal apoptosis, dysfunction in spatial memory, reduction in NR2B, enhancement of oxidative stress, and activation of ERK1/2 pathway. The present study provides clue for the notion that E2 has therapeutic potential for both prevention and intervention of TBI‐induced brain damages.
Concentration‐dependent metabolic effects of metformin in healthy and Fanconi anemia lymphoblast cells
Authors: Ravera Silvia , Cossu Vanessa , Tappino Barbara , Nicchia Elena , Dufour Carlo , Cavani Simona , Sciutto Andrea , Bolognesi Claudia , Columbaro Marta , Degan Paolo , Cappelli Enrico
Published: July 2017

Metformin (MET) is the drug of choice for patients with type 2 diabetes and has been proposed for use in cancer therapy and for treating other metabolic diseases. More than 14,000 studies have been published addressing the cellular mechanisms affected by MET. However, several in vitro studies have used concentrations of the drug 10–100‐fold higher than the plasmatic concentration measured in patients. Here, we evaluated the biochemical, metabolic, and morphologic effects of various concentrations of MET. Moreover, we tested the effect of MET on Fanconi Anemia (FA) cells, a DNA repair genetic disease with defects in energetic and glucose metabolism, as well as on human promyelocytic leukemia (HL60) cell lines. We found that the response of wild‐type cells to MET is concentration dependent. Low concentrations (15 and 150 µM) increase both oxidative phosphorylation and the oxidative stress response, acting on the AMPK/Sirt1 pathway, while the high concentration (1.5 mM) inhibits the respiratory chain, alters cell morphology, becoming toxic to the cells. In FA cells, MET was unable to correct the energetic/respiratory defect and did not improve the response to oxidative stress and DNA damage. By contrast, HL60 cells appear sensitive also at 150 μM. Our findings underline the importance of the MET concentration in evaluating the effect of this drug on cell metabolism and demonstrate that data obtained from in vitro experiments, that have used high concentrations of MET, cannot be readily translated into improving our understanding of the cellular effects of metformin when used in the clinical setting.
Salting‐out extraction of bio‐based isobutanol from an aqueous solution
Authors: Yi Conghua , Zhang Yulei , Xie Shaoqu , Song Wenli , Qiu Xueqing
Published: July 2017

BACKGROUND

More efficient downstream separation technologies need to be explored due to the low concentration of bio‐based isobutanol in the fermentation broth. The salting‐out extraction of isobutanol from its aqueous solution by employing nine salts (K4P2O7·3H2O, K2HPO4·3H2O, K3PO4·3H2O, K2CO3, K2SO4, KCl, Na2CO3, Na2SO4, NaCl) as salting‐out agents and three organic solvents (2‐ethyl‐1‐hexanol, cyclopentanol, 2‐methyl‐2‐butanol) as extractants were investigated at 298.15 K.

RESULTS

The recovery was greatly influenced by the salt concentration and types of salts and organic solvents. When the initial molar K4P2O7 concentration was equal to or higher than 1.01 mol kg‐1 and the mass ratio of aqueous isobutanol solution to 2‐ethyl‐1‐hexanol was 1:1, the recovery of isobutanol reached 100%, and more than 91.62% of water was removed from the organic phase.

CONCLUSION

The salting‐out effects of different anions in nine salts were ordered in the sequence: Cl‐ < SO42‐ < HPO42‐ < CO32‐ < PO43‐ < P2O74‐ at the same initial molar salt concentration and using the same organic solvent. 2‐Ethyl‐1‐hexanol was verified to be the most suitable extractant. The distribution behavior and salting‐out extraction effects can be evaluated by tie‐line correlations and solubility correlation. © 2017 Society of Chemical Industry
Microbial communities in carbonate rocks—from soil via groundwater to rocks
Authors: Meier Aileen , Singh Manu K. , Kastner Anne , Merten Dirk , Büchel Georg , Kothe Erika
Published: July 2017

Microbial communities in soil, groundwater, and rock of two sites in limestone were investigated to determine community parameters differentiating habitats in two lithostratigraphic untis. Lower Muschelkalk and Middle Muschelkalk associated soils, groundwater, and rock samples showed different, but overlapping microbial communities linked to carbon fluxes. The microbial diversities in soil were highest, groundwater revealed overlapping taxa but lower diversity, and rock samples were predominantly characterized by endospore forming bacteria and few archaea. Physiological profiles could establish a differentiation between habitats (soil, groundwater, rock). From community analyses and physiological profiles, different element cycles in limestone could be identified for the three habitats. While in soil, nitrogen cycling was identified as specific determinant, in rock methanogenesis linked carbonate rock to atmospheric methane cycles. These patterns specifically allowed for delineation of lithostratigraphic connections to physiological parameters.
A comprehensive data set for tropical cyclone storm surge‐induced inundation for the east coast of India
Authors: Sahoo Bishnupriya , Bhaskaran Prasad K.
Published: July 2017

The Indian Ocean region is one among the six major cyclone prone regions in the world with an annual average of about five to six cyclones. Prior studies conducted for this region are location‐specific and confined to storm surge characteristic and associated inundation. A detailed study to develop precomputed scenarios on storm surge and inundation maps for the entire Indian coast is still lacking for emergency preparedness. An effort in this direction can drastically reduce preparedness time in the eventuality of a real cyclone approaching its landfall location for effective coastal zone management measures. The present study is a motivation in this direction leading to the generation of a comprehensive data set on storm surges and associated coastal flooding for entire Odisha coast located in the east coast of India and that can be extended to other coastal regions as well. Historically, the Odisha State experiences highest number of cyclone strikes with the highest risk of exposure to storm surge and inundation. The novelty of this study is in the preparation of a comprehensive storm data set using synthetic tracks simulated with various combinations of landfall location, angle of attack, intensity, and forward translation speed. It also generates possible storm surge and inundation associated with intensified cyclones expected in a changing climate scenario. Further, the study also correlates power dissipation index with storm tide all along this coast. The distribution of surge height follows a third‐order polynomial to wind speed. An in‐depth analysis was also carried out to understand the characteristics of storm surge height and extent of coastal inundation with respect to coastal geomorphology, angle of attack, and varying forward speed of cyclones. The authors believe that information and analysis from this comprehensive data set will have immense potential in understanding the impacts from tropical cyclone climatology and disaster management applications.
Augmentation of fracture healing by hydroxyapatite/collagen paste and bone morphogenetic protein‐2 evaluated using a rat femur osteotomy model
Authors: Wei Xuetao , Egawa Satoru , Matsumoto Renpei , Yasuda Hiroaki , Hirai Keigo , Yoshii Toshitaka , Okawa Atsushi , Nakajima Takehiko , Sotome Shinichi
Published: July 2017

In fracture treatment, biological bone union generally depends on the bone's natural fracture healing capacity, even in surgically treated cases. Hydroxyapatite/collagen composite (HAp/Col) has high osteoconductivity and stimulates osteogenic progenitors. Furthermore, it has the potent capacity to adsorb bone morphogenetic proteins (BMPs). In this study, we prepared an injectable HAp/Col paste and evaluated its augmentation of bone union. Furthermore, the effect of HAp/Col paste combined with BMP‐2 was also evaluated. We used a rat femur osteotomy model with a defect size of 1 mm. Male Wistar rats were assigned to one of the following four groups; a control group without any implant, a HAp/Col implant group, a group that received an absorbable collagen sponge (ACS) implant impregnated with BMP‐2 (1 μg), and a group that received a HAp/Col implant impregnated with BMP‐2 implant. Micro‐CT analysis, three‐point bending tests, and histological evaluation were performed. Bone union was achieved in two of eight cases in the HAp/Col group, five of eight cases in the ACS + BMP‐2 group, and all cases in the HAp/Col + BMP‐2 group at 8 weeks post‐surgery. The control group did not achieve bone union. In addition, in the HAp/Col + BMP‐2 group, the biomechanical strength of the fused femurs was comparable to that of the contralateral intact femur; the ratio of the mechanical load at the breaking point of the osteotomy side relative to that of the contralateral side was 1.00 ± 0.151 (SD). These results indicate that HAp/Col paste with or without BMP‐2 augments bone union. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:129–137, 2018.
Growth plate expression profiling: Large and small breed dogs provide new insights in endochondral bone formation
Authors: Teunissen Michelle , Riemers Frank M. , van Leenen Dik , Groot Koerkamp Marian J. A. , Meij Björn P. , Alblas Jacqueline , Penning Louis C. , Miranda‐Bedate Alberto , Tryfonidou Marianna A.
Published: July 2017

The difference in the adult height of mammals, and hence in endochondral bone formation, is not yet fully understood and may serve to identify targets for bone and cartilage regeneration. In line with this hypothesis, the intra‐species disparity between the adult height of Great Danes and Miniature Poodles was investigated at a transcriptional level. Microarray analysis of the growth plate of five Great Danes and five Miniature Poodles revealed 2,981 unique genes that were differentially expressed, including many genes with an unknown role in skeletal development. A signaling pathway impact analysis indicated activation of the cell cycle, extracellular matrix receptor interaction and the tight junction pathway, and inhibition of pathways associated with inflammation and the complement cascade. In additional validation steps, the gene expression profile of the separate growth plate zones for both dog breeds were determined. Given that the BMP signaling is known for its crucial role in skeletal development and fracture healing, and BMP‐2 is used in orthopaedic and spine procedures for bone augmentation, further investigations concentrated on the BMP pathway.The canonical BMP‐2 and BMP‐6 signaling pathway was activated in the Great Danes compared to Miniature Poodles. In conclusion, investigating the differential expression of genes involved in endochondral bone formation in small and large breed dogs, could be a game changing strategy to provide new insights in growth plate development and identify new targets for bone and cartilage regeneration. © 2017 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 36:138–148, 2018.
Diagnostics for generalized linear hierarchical models in network meta‐analysis
Authors: Zhao Hong , Hodges James S. , Carlin Bradley P.
Published: July 2017

Network meta‐analysis (NMA) combines direct and indirect evidence comparing more than 2 treatments. Inconsistency arises when these 2 information sources differ. Previous work focuses on inconsistency detection, but little has been done on how to proceed after identifying inconsistency. The key issue is whether inconsistency changes an NMA's substantive conclusions. In this paper, we examine such discrepancies from a diagnostic point of view. Our methods seek to detect influential and outlying observations in NMA at a trial‐by‐arm level. These observations may have a large effect on the parameter estimates in NMA, or they may deviate markedly from other observations. We develop formal diagnostics for a Bayesian hierarchical model to check the effect of deleting any observation. Diagnostics are specified for generalized linear hierarchical NMA models and investigated for both published and simulated datasets. Results from our example dataset using either contrast‐ or arm‐based models and from the simulated datasets indicate that the sources of inconsistency in NMA tend not to be influential, though results from the example dataset suggest that they are likely to be outliers. This mimics a familiar result from linear model theory, in which outliers with low leverage are not influential. Future extensions include incorporating baseline covariates and individual‐level patient data.