bluuebunny/crossref_metadata_2025_split huggingface dataset:
Birth of the eukaryotes by a set of reactive innovations: New insights force us to relinquish gradual models
Authors: Speijer Dave 
Published: November 2015

Of two contending models for eukaryotic evolution the “archezoan“ has an amitochondriate eukaryote take up an endosymbiont, while “symbiogenesis“ states that an Archaeon became a eukaryote as the result of this uptake. If so, organelle formation resulting from new engulfments is simplified by the primordial symbiogenesis, and less informative regarding the bacterium‐to‐mitochondrion conversion. Gradualist archezoan visions still permeate evolutionary thinking, but are much less likely than symbiogenesis. Genuine amitochondriate eukaryotes have never been found and rapid, explosive adaptive periods characteristic of symbiogenetic models explain this. Mitochondrial proteomes, encoded by genes of “eukaryotic origin“ not easily linked to host or endosymbiont, can be understood in light of rapid adjustments to new evolutionary pressures. Symbiogenesis allows “expensive” eukaryotic inventions via efficient ATP generation by nascent mitochondria. However, efficient ATP production equals enhanced toxic internal ROS formation. The synergistic combination of these two driving forces gave rise to the rapid evolution of eukaryotes.Also watch the Video Abstract.
An ultra scale‐down approach identifies host cell protein differences across a panel of mAb producing CHO cell line variants
Authors: Hogwood Catherine E.M. , Ahmad Shahina S. , Tarrant Richard D. , Bracewell Daniel G. , Smales C. Mark 
Published: November 2015

AbstractDuring the manufacture of biopharmaceutical products, the final product must lie within strict pre‐set specifications, for example the host cell protein (HCP) content. A number of specific HCPs have been identified in particular products and the interactions between product/HCPs have also been recently investigated; however, a comparison of the HCP dynamics between related cell lines and their response to early downstream processing to aid process development and cell line selection has not been published. We have utilised a proteomic approach coupled with an ultra scale‐down study to determine the HCP profile dynamics, at harvest and during early downstream processing, across a panel of recombinant GS‐CHOK1SV antibody producing cell lines. The results reveal that cell culture viability upon harvest has the greatest impact upon shear sensitivity and HCP concentration. Whilst the general HCP population/profile was broadly similar across the cell lines, the actual amounts of some specific HCPs in the supernatant differed and a number of cell line specific differences in the response to early downstream processing were observed. We anticipate that such knowledge can now be applied to cell line selection and downstream processing development to target reduction/removal of general and specific problematic HCPs before and during downstream processing.
Pro‐region engineering for improved yeast display and secretion of brain derived neurotrophic factor
Authors: Burns Michael L. , Malott Thomas M. , Metcalf Kevin J. , Puguh Arthya , Chan Jonah R. , Shusta Eric V. 
Published: November 2015

AbstractBrain derived neurotrophic factor (BDNF) is a promising therapeutic candidate for a variety of neurological diseases. However, it is difficult to produce as a recombinant protein. In its native mammalian context, BDNF is first produced as a pro‐protein with subsequent proteolytic removal of the pro‐region to yield mature BDNF protein. Therefore, in an attempt to improve yeast as a host for heterologous BDNF production, the BDNF pro‐region was first evaluated for its effects on BDNF surface display and secretion. Addition of the wild‐type pro‐region to yeast BDNF production constructs improved BDNF folding both as a surface‐displayed and secreted protein in terms of binding its natural receptors TrkB and p75, but titers remained low. Looking to further enhance the chaperone‐like functions provided by the pro‐region, two rounds of directed evolution were performed, yielding mutated pro‐regions that further improved the display and secretion properties of BDNF. Subsequent optimization of the protease recognition site was used to control whether the produced protein was in pro‐ or mature BDNF forms. Taken together, we have demonstrated an effective strategy for improving BDNF compatibility with yeast protein engineering and secretion platforms.
Development and application of a UPLC‐MS/MS method for simultaneous determination of fenofibric acid and berberine in rat plasma: application to the drug–drug pharmacokinetic interaction study of fenofibrate combined with berberine after oral administration in rats
Authors: Li Guofei , Yang Fan , Liu Mei , Su Xianying , Zhao Mingming , Zhao Limei 
Published: November 2015

Abstract:With the purpose of carrying out pharmacokinetic interaction studies ofnberberine (BBR) and fenofibrate (FBT), an UPLC‐MS/MS method has been developed and validated. The analytes, BBR and fenofibric acid (FBA, metabolite of FBT) and the internal standard, tetrahydropalmatine, were extracted with dichloromethane–diethyl ether (3:2, v/v) and separated on an Agilent Eclipse XDB C18 column using a mobile phase composed of acetonitrile and water. With positive ion electrospray ionization, the analytes were monitored on a triple quadrupole mass spectrometer in multiple reaction monitoring mode. Linear calibration curves were obtained over the concentration ranges of 0.1–100.0 ng/mL for BBR and 10.0–50,000.0 ng/mL for FBA. For BBR and FBA, the intra‐ and inter‐day precisions were <11.5 and 11.9%, respectively. The accuracy was within 11.7% and 11.3%. The mean recoveries of BBR at three concentrations of 0.2, 20.0, 80.0 ng/mL were >85.6%, and those of FBA at three concentrations of 20.0, 2500.0, 40,000.0 ng/mL were >87.9%. Consequently, the proposed method was applied to the pharmacokinetic interaction study of FBT combined with BBR after oral administration in rats and was proved to be sensitive, specific and reliable to analyze BBR and FBA in biological samples simultaneously. Copyright © 2016 John Wiley & Sons, Ltd.
An HPLC method for the determination of a novel anti‐hypertension agent 6,7‐dimethoxy‐3‐[4‐(4‐fluorobenzyloxy)‐3‐methoxyphenylmethyl]quinazolin‐4(3H)‐one in rat plasma: application to pharmacokinetic study
Authors: Chang Rui‐Miao , Zeng Ai‐Guo , Du Wei , Xu Xin‐Ya , Zuo Sai‐Jie , Chang Chun , Fu Qiang 
Published: November 2015

Abstract6,7‐Dimethoxy‐3‐[4‐(4‐fluorobenzyloxy)‐3‐methoxyphenylmethyl] quinazolin‐4(3H)‐one (DFMQ‐19), a novel analog of 3‐benzylquinazolin‐4(3H)‐ones, may be considered as a drug candidate for the treatment of hypertension. The aim of this study was to develop and validate a reverse‐phase high‐performance liquid chromatography to determine the DFMQ‐19 in plasma and demonstrate its application in pharmacokinetic studies. Separation of DFMQ‐19 and IS (structural analog of DFMQ‐19) was performed using a Shim‐Pack VP‐ODS column and a mixture of acetonitrile and water as mobile phase. The HPLC method was validated according to the International Conference on Harmonization guidelines. The limit of detection and lower limit of quantitation were 0.05 and 0.1 μg/mL, respectively. The recovery rate of DFMQ‐19 from blood samples was >81% of the spiked amount. The RSD of the intra‐ and inter‐day precisions was within 7.5%, and RE of accuracy was between −14.4 and 4.5%. This method was successfully applied to the pharmacokinetic study after administration of DFMQ‐19. The pharmacokinetic parameters, such as half‐life, mean residence time and maximum concentration were determined. Based on these pharmacokinetic parameters, the oral bioavailability of DFMQ‐19 was calculated to be 13.42% in rat. Copyright © 2016 John Wiley & Sons, Ltd.
Gasification of Microalgae Using Supercritical Water and the Potential of Effluent Recycling
Authors: Elsayed Sherif , Boukis Nikolaos , Patzelt Dominik , Hindersin Stefan , Kerner Martin , Sauer Jörg 
Published: November 2015

AbstractThe gasification of microalgae in supercritical water was investigated in this work. The product gas contained mainly H2, CO2, CH4, and C2H6. Operation at high temperatures and lower biomass concentrations resulted in the highest carbon gasification efficiency and the lowest total organic carbon levels in the residual water. Due to its content of inorganic nutrients, the residual water was applied as cultivation medium for microalgae. However, algal growth in the untreated residual water was inhibited by the existence of potentially toxic substances evolved from gasification. Upon treatment by activated carbon filtration and ultraviolet light degradation, these substances were eliminated and cultivation in the residual water was possible. The major fraction of inorganic residues from gasification was recovered by means of water purging, increasing the potential of nutrient recycling for cultivation.
Mid‐Infrared Spectroscopy for Monitoring of Anaerobic Digestion Processes – Prospects and Challenges
Authors: Eccleston Robin , Wolf Christian , Balsam Matthias , Schulte Franziska , Bongards Michael , Rehorek Astrid 
Published: November 2015

AbstractTo develop an online probe that is not only sufficiently robust, but also able to measure crucial process variables in biogas plants is a tough challenge. Therefore, a mid‐infrared (MIR) spectroscopic attenuated total reflection (ATR) probe and robust probe fitting were established. A fully automated probe control, calibration after probe cleaning, and analysis of the absorption spectra using machine learning were implemented in order to reduce maintenance of the probe to a minimum. The relevant wavelengths in the MIR spectrum for organic acids, total alkalinity, and ammonium nitrogen concentration were identified. Finally, intensive lab testing was carried out, followed by operation of the complete online measurement system at an industrial biogas plant. In order to improve signal strength and sensitivity, microelectronic mechanical system (MEMS)‐based Fabry‐Pérot interferometers were also investigated.
Crystallisation from a Water‐in‐Oil Emulsion as a Route to Enantiomer Separation: The Case of dl‐Threonine
Authors: Gilks Sara E. , Davey Roger J. 
Published: November 2015

AbstractThe use of crystalliation as a means of separating enantiomers is well known. The utility of commonly applied seeding approaches is limited by the ultimate crystallisation of the antipode. Here we demonstrate how the combination of colloid science and crystal chemistry can lead to an emulsion based process yielding robust separation of a purified solid and impure liquid phases with ultimate product ee of up to 90 %. Threonine is used as a model to demonstrate the viability of the method but it is clear that extension to include, for example, simultaneous racemisation within the disperse phase is easily possible and would transform this from a separation to a preparation process.
Reversed Crystal Growth of RHO Zeolitic Imidazolate Framework (ZIF)
Authors: Self Katherine , Telfer Michael , Greer Heather F. , Zhou Wuzong 
Published: November 2015

AbstractRHO zeolitic imidazolate framework (ZIF), Zn1.33(O.OH)0.33(nim)1.167(pur), crystals with a rhombic dodecahedral morphology were synthesized by a solvothermal process. The growth of the crystals was studied over time using scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X‐ray diffraction (PXRD) and Brunauer–Emmett–Teller (BET) analyses, and a reversed crystal growth mechanism was revealed. Initially, precursor materials joined together to form disordered aggregates, which then underwent surface recrystallization forming a core–shell structure, in which a disordered core is encased in a layer of denser, less porous crystal. When the growth continued, the shell became less and less porous, until it was a layer of true single crystal. The crystallization then extended from the surface to the core over a six‐week period until, eventually, true single crystals were formed.
Synthesis and Biological Evaluation of Lactimidomycin and Its Analogues
Authors: Larsen Brian J. , Sun Zhankui , Lachacz Eric , Khomutnyk Yaroslav , Soellner Matthew B. , Nagorny Pavel 
Published: November 2015

AbstractThe studies culminating in the total synthesis of the glutarimide‐containing eukaryote translation elongation inhibitor lactimidomycin are described. The optimized synthetic route features a ZnII‐mediated intramolecular Horner–Wadsworth–Emmons (HWE) reaction resulting in a highly stereoselective formation of the strained 12‐membered macrolactone of lactimidomycin on a 423 mg scale. The presence of the E,Z‐diene functionality was found to be key for effective macrocyclizations as a complete removal of these unsaturation units resulted in exclusive formation of the dimer rather than monocyclic enoate. The synthetic route features a late‐stage installation of the glutarimide functionality via an asymmetric catalytic Mukaiyama aldol reaction, which allows for a quick generation of lactimidomycin homolog 55 containing two additional carbons in the glutarimide side chain. Similar to lactimidomycin, this analog was found to possess cytotoxicity against MDA‐MB‐231 breast cancer cells (GI50=1–3 μM) using in vitro 2D and 3D assays. Although lactimidomycin was found to be the most potent compound in terms of anticancer activity, 55 as well as truncated analogues 50–52 lacking the glutarimide side‐chain were found to be significantly less toxic against human mammary epithelial cells.
Determination of sperm concentration using flow cytometry with simultaneous analysis of sperm plasma membrane integrity in zebrafish Danio rerio
Authors: Yang Huiping , Daly Jonathan , Tiersch Terrence R. 
Published: November 2015

AbstractControl of sperm concentration is required to ensure consistent and reproducible results for cryopreservation and in vitro fertilization protocols. Determination of sperm concentration is traditionally performed with a counting chamber (e.g., hemocytometer), or more recently with a spectrophotometer. For small‐sized biomedical model fishes, the availability of sperm sample is limited to microliters, so it is desirable to develop fast and accurate approaches for concentration determination that also minimize sample use. In this study, a new approach was developed for sperm concentration determination using a flow cytometer (Accuri C6, BD Biosciences, San Jose, CA) with simultaneous measurement of sperm membrane integrity after fluorescent staining with SYBR®−14 and propidium iodide (PI) in sperm from Zebrafish Danio rerio. The goal was to develop a protocol for simultaneous determination of sperm quality and quantity by flow cytometry. The objectives were to (1) determine the effects of sample volume (250 and 500 µl) and analysis volume (10 and 50 µl) on the accuracy of particle counting using standard volumetric validation beads; (2) identify the effective range of sperm concentrations that flow cytometry can measure; (3) test the precision and reproducibility of the sperm concentration measurements; and (4) verify the flow cytometry approach by comparison with measurement with a hemocytometer and a microspectrophotometer. Sample volumes of 250 and 500 µl and analysis volumes of 10 and 50 µl did not affect bead count with the factory‐set flow rates of “medium” or “fast,” and the precision and accuracy was retained across a concentration range of 1 × 103−1 × 107 cells/ml. The approach developed in this study was comparable to traditional methodologies such as hemocytometer or microspectrophotometer. This study provides an efficient, accurate, and rapid method for determination of sperm concentration using flow cytometry while providing simultaneous assessment of sperm membrane integrity. Such approaches can reduce the time needed for quantity assessment and maximize the use of valuable sperm samples. © 2015 International Society for Advancement of Cytometry
Perceived coercion in inpatients with Anorexia nervosa: Associations with illness severity and hospital course
Authors: Schreyer Colleen C. , Coughlin Janelle W. , Makhzoumi Saniha H. , Redgrave Graham W. , Hansen Jennifer L. , Guarda Angela S. 
Published: November 2015

ABSTRACTObjectiveThe use of coercion in the treatment for anorexia nervosa (AN) is controversial and the limited studies to date have focused on involuntary treatment. However, coercive pressure for treatment that does not include legal measures is common in voluntarily admitted patients with AN. Empirical data examining the effect of non‐legal forms of coerced care on hospital outcomes are needed.MethodParticipants (N = 202) with AN, Avoidant/Restrictive Food Intake Disorder (ARFID), or subthreshold AN admitted to a hospital‐based behavioral specialty program completed questionnaires assessing illness severity and perceived coercion around the admissions process. Hospital course variables included inpatient length of stay, successful transition to a step‐down partial hospitalization program, and achievement of target weight prior to program discharge.ResultsHigher perceived coercion at admission was associated with increased drive for thinness and body dissatisfaction, but not with admission BMI. Perceived coercion was not related to inpatient length of stay, rate of weight gain, or achievement of target weight although it was predictive of premature drop‐out prior to transition to an integrated partial hospitalization program.DiscussionThese results, from an adequately powered sample, demonstrate that perceived coercion at admission to a hospital‐based behavioral treatment program was not associated with rate of inpatient weight gain or achieving weight restoration, suggesting that coercive pressure to enter treatment does not necessarily undermine formation of a therapeutic alliance or clinical progress. Future studies should examine perceived coercion and long‐term outcomes, patient views on coercive pressures, and the effect of different forms of leveraged treatment. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:407–412).
Uranyl Complexes with (Meth)acrylate Anions
Authors: Klepov Vladislav V. , Serezhkina Larisa B. , Pushkin Denis V. , Alekseev Evgeny V. , Grigor'ev Mikhail S. , Sergeeva Olga A. , Shimin Nikita A. , Serezhkin Victor N. 
Published: November 2015

AbstractTwo isostructural series with general formulae [R(H2O)6][UO2(CH2CHCOO)3]2 (R = Mg, Co, or Ni) and [R(H2O)6][UO2{CH2C(CH3)COO}3]2·8H2O (R = Mg or Zn) have been synthesized and characterized by single‐crystal X‐ray diffraction and IR spectroscopy. The acrylate and methacrylate series of complexes crystallize in the monoclinic crystal system with the space groups P21/c and P21/n, respectively. The crystal structures of all the studied compounds have similar main structural units, specifically, octahedral aqua complexes [R(H2O)6]2+ and tris(carboxylato) complexes [UO2L3]– (L = acrylate or methacrylate anion). Despite this, there are significant structural differences between the two series that lead to the inclusion of outer‐sphere water molecules in the structures of the methacrylate series. The intermolecular interactions in the acrylate series were studied by the method of molecular Voronoi–Dirichlet polyhedra and compared with those in previously studied acetate compounds. The structures of the methacrylate series of complexes demonstrate an important role of π···π interactions in the molecular packing of the complexes.
Effect of tamarind (Tamarindus indica L.) seed on antioxidant activity, phytocompounds, physicochemical characteristics, and sensory acceptability of enriched cookies and mango juice
Authors: Natukunda Sheilla , Muyonga John H. , Mukisa Ivan M. 
Published: November 2015

AbstractTamarind seeds are not consumed despite their high antioxidative activity. In this study, 0–10% tamarind seed powder (TSP) was incorporated into mango juice and cookies. Total phenolics (Folin–Ciocalteu assay), antioxidant activity (2,2‐diphenyl‐1 picrylhydrazyl (DPPH) radical scavenging assay), flavonoid (aluminum chloride assay), condensed tannins content (Vanillin‐HCl assay), and consumer acceptability (n = 50) of the products were determined. TSP increased the pH and viscosity and reduced titratable acidity of juice. Incorporation of TSP increased the: total phenolic content (6.84 ± 0.21 to 88.44 ± 0.8 mg GAE/100 mL); flavonoid (4.64 ± 0.03–21.7 ± 0.36 mg CE/100 mL); condensed tannins (0.24 ± 0.01–21.81 ± 0.08 mg CE/100 mL) and total antioxidant activity (4.65 ± 0.88–21.70 ± 0.03 mg VCE/100 mL) of juice. A similar trend was observed for cookies. Maximum sensorially acceptable TSP levels were 1.5% and 6%, respectively, for juice and cookies. TSP can thus be utilized as a source of natural antioxidants in food products.
Effect of environment and genotypes on the physicochemical quality of the grains of newly developed wheat inbred lines
Authors: Mutwali Noha I. A. , Mustafa Abdelmoniem I. , Gorafi Yasir S. A. , Mohamed Ahmed Isam A. 
Published: November 2015

AbstractTo meet the increased demand for wheat consumption, wheat cultivation in Sudan expanded southward to latitudes lower than 15°N, entering a new and warmer environment. Consequently, wheat breeders developed several wheat genotypes with high yields under these environmental conditions; however, the evaluation of the end‐use quality of these genotypes is scarce. In this study, we assessed the end‐use quality attributes of 20 wheat genotypes grown in three different environments in the Sudan (Wad Medani, Hudeiba, and Dongola). The results showed significant differences (P ≤ 0.01) in all quality tests among environments, genotypes and genotypes Versus environments. The findings obtained, covered wide ranges of test weight (TW, 76.6–85.25 kg/hL), thousand kernel weight (TKW, 28.70–48.48 g), protein (PC, 9.96–14.06%), wet gluten (WG, 28.63–46.53%), gluten index (GI, 36.36–92.77%), water holding capacity (WHC, 168.42–219.32%), falling number (FN, 508.00–974.67 sec), and sedimentation value (SV, 19.00–40.00 mL). Analysis of the traits, genotypes, and traits versus genotypes showed varied correlations in the three growing environments. The genotype G3 grown in either one or all of the three environments exhibits worthy performance and stability for most of the tested quality traits. The crossing of this genotype with high yield genotypes could produce cultivars with sufficient quality and marketability.
Factors associated with the sensitivity of fine‐needle aspiration cytology for the diagnosis of follicular variant papillary thyroid carcinoma
Authors: Chai Young Jun , Suh Hyunsuk , Yi Jin Wook , Yu Hyeong Won , Lee Joon‐Hyop , Kim Su‐jin , Won Jae‐Kyung , Lee Kyu Eun 
Published: November 2015

BackgroundThe purpose of this study was to evaluate the factors associated with diagnostic accuracy of preoperative fine‐needle aspiration (FNA) for follicular variant papillary thyroid carcinoma (FVPTC).MethodsThe patients with FVPTC who underwent thyroidectomy were divided into 2 groups: “group A” (Bethesda category II, III, or IV) versus “group B” (category V or VI).ResultsA total of 225 patients (117 in group A and 108 in group B) were included. Group B was associated with older age, malignant ultrasonographic features, smaller tumor size, extrathyroidal extension, higher stage, and B‐type Raf (BRAF)V600E mutation compared with group A. In multivariable analysis, malignant ultrasonographic features and tumor size ≤3.0 cm were independent predictive factors for group B.ConclusionFVPTCs >3.0 cm are unlikely to be diagnosed as category V or VI. Clinicians should keep FVPTC in mind and consider diagnostic lobectomy for the nodules regardless of FNA or ultrasonographic findings. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1467–E1471, 2016