bluuebunny/crossref_metadata_2025_split huggingface dataset:
Binding of methacycline to human serum albumin at subdomain IIA using multispectroscopic and molecular modeling methods
Authors: Dong Chengyu , Lu Ningning , Liu Ying 
Published: December 2012

ABSTRACTThis study was designed to examine the interaction of methacyline (METC) with human serum albumin (HSA) by multispectroscopy and a molecular modeling method under simulative physiological conditions. The quenching mechanism was suggested to be static quenching based on fluorescence and ultraviolet–visible (UV–Vis) spectroscopy. According to the Vant' Hoff equation, the values of enthalpy (∆H) and entropy change (∆S) were calculated to be −95.29 kJ/mol and −218.13 J/mol/K, indicating that the main driving force of the interaction between HSA and METC were hydrogen bonds and van der Waals's forces. By performing displacement measurements, the specific binding of METC in the vicinity of Sudlow's site I of HSA was clarified. An apparent distance of 3.05 nm between Trp214 and METC was obtained via the fluorescence resonance energy transfer (FRET) method. Furthermore, the binding details between METC and HSA were further confirmed by molecular docking studies, which revealed that METC was bound at subdomain IIA through multiple interactions, such as hydrophobic effect, polar forces, hydrogen bonding, etc. The results of three‐dimensional fluorescence and Fourier transform infrared (FTIR) spectroscopy showed that METC caused conformational and some microenvironmental changes in HSA and reduced the α‐helix significantly in the range of 52.3−40.4% in HSA secondary structure. Moreover, the coexistence of metal ions such as Ca2+, Al3+, Fe3+, Zn2+, Cu2+, Cr3+ and Cd2+ can decrease the binding constants of METC–HSA. Copyright © 2012 John Wiley & Sons, Ltd.
Expanded complexity of unstable repeat diseases
Authors: Polak Urszula , McIvor Elizabeth , Dent Sharon Y.R. , Wells Robert D. , Napierala Marek 
Published: December 2012

AbstractUnstable repeat diseases (URDs) share a common mutational phenomenon of changes in the copy number of short, tandemly repeated DNA sequences. More than 20 human neurological diseases are caused by instability, predominantly, expansion of microsatellite sequences. Changes in the repeat size initiate a cascade of pathological processes, frequently characteristic of a unique disease or a small subgroup of the URDs. Understanding of both the mechanism of repeat instability and molecular consequences of the repeat expansions is critical to developing successful therapies for these diseases. Recent technological breakthroughs in whole genome, transcriptome and proteome analyses will almost certainly lead to new discoveries regarding the mechanisms of repeat instability, the pathogenesis of URDs, and will facilitate development of novel therapeutic approaches. The aim of this review is to give a general overview of unstable repeats diseases, highlight the complexities of these diseases, and feature the emerging discoveries in the field. © 2012 BioFactors, 2013
H2S: A “Double face” molecule in health and disease
Authors: Masi Alessandra di , Ascenzi Paolo 
Published: December 2012

AbstractH2S is a colorless, poisonous, and flammable gas with the characteristic foul odor of rotten eggs. H2S is present in effluent from hydrothermal vents and sulfur springs, which have been proposed to act as “pores” in the Earth surface, providing a source of energy in the form of reducing equivalents and of iron‐sulfur centers. Remarkably, H2S‐producing machineries or H2S‐utilization capacity remain within a great diversity of microorganisms. In particular, two classes of bacteria have been identified, that is, sulfate‐ and sulfur‐reducing and sulfur‐oxidizing bacteria, both contributing to the balance of the H2S level. The human body produces H2S and uses it as a signaling molecule in several physiological processes. However, many diseases, including neurological diseases, cardiovascular diseases, inflammation, and metabolic disorders, have been linked to abnormal endogenous H2S functions and metabolism. Remarkably, in recent years, the therapeutic administration of H2S(‐donors) appears relevant in the treatment of some diseases. Here, H2S metabolism, as well as its physiological and pathological roles in humans is reviewed. Furthermore, the therapeutic use of H2S is discussed. © 2012 BioFactors, 2013
Engineering superficial zone features in tissue engineered cartilage
Authors: Chen Tony , Hilton Matthew J. , Brown Edward B. , Zuscik Michael J. , Awad Hani A. 
Published: December 2012

AbstractA major challenge in cartilage tissue engineering is the need to recreate the native tissue's anisotropic extracellular matrix structure. This anisotropy has important mechanical and biological consequences and could be crucial for integrative repair. Here, we report that hydrodynamic conditions that mimic the motion‐induced flow fields in between the articular surfaces in the synovial joint induce the formation of a distinct superficial layer in tissue engineered cartilage hydrogels, with enhanced production of cartilage matrix proteoglycan and Type II collagen. Moreover, the flow stimulation at the surface induces the production of the surface zone protein Proteoglycan 4 (aka PRG4 or lubricin). Analysis of second harmonic generation signature of collagen in this superficial layer reveals a highly aligned fibrillar matrix that resembles the alignment pattern in native tissue's surface zone, suggesting that mimicking synovial fluid flow at the cartilage surface in hydrodynamic bioreactors could be key to creating engineered cartilage with superficial zone features. Biotechnol. Bioeng. 2013; 110: 1476–1486. © 2012 Wiley Periodicals, Inc.
Permeability of a growing biofilm in a porous media fluid flow analyzed by magnetic resonance displacement‐relaxation correlations
Authors: Vogt Sarah J. , Sanderlin Alexis B. , Seymour Joseph D. , Codd Sarah L. 
Published: December 2012

AbstractBiofilm growth in porous media is difficult to study non‐invasively due to the opaqueness and heterogeneity of the systems. Magnetic resonance is utilized to non‐invasively study water dynamics within porous media. Displacement‐relaxation correlation experiments were performed on fluid flow during biofilm growth in a model porous media of mono‐dispersed polystyrene beads. The spin–spinT2magnetic relaxation distinguishes between the biofilm phase and bulk fluid phase due to water–biopolymer interactions present in the biofilm, and the flow dynamics are measured using PGSE NMR experiments. By correlating these two measurements, the effects of biofilm growth on the fluid dynamics can be separated into a detailed analysis of both the biofilm phase and the fluid phase simultaneously within the same experiment. Within the displacement resolution of these experiments, no convective flow was measured through the biomass. An increased amount of longitudinal hydrodynamic dispersion indicates increased hydrodynamic mixing due to fluid channeling caused by biofilm growth. The effect of different biofilm growth conditions was measured by varying the strength of the bacterial growth medium. Biotechnol. Bioeng. 2013; 110: 1366–1375. © 2012 Wiley Periodicals, Inc.
The women on stieve's list: Victims of national socialism whose bodies were used for anatomical research
Authors: Hildebrandt Sabine 
Published: December 2012

AbstractResearch on the history of anatomy in the Third Reich has often concentrated on the influence of the National Socialist (NS) regime on anatomists and their consequent unethical activities. Only recently, the focus has shifted to NS victims whose bodies were used for anatomical purposes. As a first approach to learning more about the victims, this study investigated the persons whose names Hermann Stieve, chairman of the Anatomical Department at the University of Berlin, had listed after using their bodies for his research. The study draws a group portrait and recounts selected biographies of the 174 women and eight men on the list. Most women were of reproductive age, two‐thirds were German and a majority was executed for political reasons. Among the executed were at least two pregnant women. The corrected names, biographical data, and nationalities of all persons on the list are published here. None of them volunteered to be dissected, nor were the anatomists at the time interested in the victims' personal background. Future work will have to focus on the investigation of further biographies so that numbers can be turned back into people. This history is a reminder to modern anatomy that ethical body procurement and the anatomists' caring about the body donor is of the utmost importance in a discipline that introduces students to professional ethics in the medical teaching curriculum. Clin. Anat. 26:3–21, 2013. © 2012 Wiley Periodicals, Inc.
Early detection of clinically significant prostate cancer at diagnosis: a prospective study using a novel panel of TMPRSS2:ETS fusion gene markers
Authors: Chan Sam W. , Nguyen Phuong‐Nam , Violette Philippe , Brimo Fadi , Taguchi Yosh , Aprikian Armen , Chen Junjian Z. 
Published: December 2012

AbstractWe explore noninvasive clinical applications of multiple disease‐specific fusion markers recently discovered in prostate cancer to predict the risk of cancer occurrence and aggressiveness at diagnosis. A total of 92 men who were prostate‐specific antigen (PSA) screened and scheduled for diagnostic biopsy were enrolled for this study. Prospectively collected urine was blind coded for laboratory tests. RNA from urine sediments was analyzed using a panel of 6 TMPRSS2:ETS fusion markers with a sensitive quantitative PCR platform. The pathology reported 39 biopsy‐positive cases from 92 patients (42.4%). In urine test, 10 unique combinations of fusion types were detected in 32 of 92 (34.8%) prebiopsy samples. A novel combination of fusion markers, termed Fx (III, IV, ETS), was identified with a sensitivity of 51.3% and an odds ratio of 10.1 in detecting cancer on biopsy. Incorporating a categorical variable of Fx (III, IV, ETS) with urine PCA3 and serum PSA, a regression model was developed to predict biopsy outcomes with an overall accuracy of 77%. Moreover, the overexpression of Fx (III, IV, or ETS) was shown to be an independent predictor to the high‐grade cancer, with a predictive accuracy of 80% when coupled with PSA density. The individualized risk scores further stratified a high‐risk group that is composed of 92% high‐grade cancers and a low‐risk group that harbors mainly clinically insignificant cancers. In conclusion, we have identified a novel combination of fusion types very specific to the clinically significant prostate cancer and developed effective regression models to predict biopsy outcomes and aggressive cancers at diagnosis.
Boron‐Based Inhibitors of Acyl Protein Thioesterases 1 and 2
Authors: Zimmermann Tobias J. , Bürger Marco , Tashiro Etsu , Kondoh Yasumitsu , Martinez Nancy E. , Görmer Kristina , Rosin‐Steiner Sigrid , Shimizu Takeshi , Ozaki Shoichiro , Mikoshiba Katsuhiko , Watanabe Nobumoto , Hall Dennis , Vetter Ingrid R. , Osada Hiroyuki , Hedberg Christian , Waldmann Herbert 
Published: December 2012

AbstractRas proteins are of importance in cell proliferation, and hence their mutated forms play causative roles in many kinds of cancer in different tissues. Inhibition of the Ras‐depalmitoylating enzyme acyl protein thioesterases APT1 and ‐2 is a new approach to modulating the Ras cycle. Here we present boronic and borinic acid derivatives as a new class of potent and nontoxic APT inhibitors. These compounds were detected by extensive library screening using chemical arrays and turned out to inhibit human APT1 and ‐2 in a competitive mode. Furthermore, one of the molecules was demonstrated to inhibit Erk1/2 phosphorylation significantly.
A Synthetic, Species‐Specific Activator of Secondary Metabolism and Sporulation in Streptomyces coelicolor
Authors: Ahmed Salman , Craney Arryn , Pimentel‐Elardo Sheila M. , Nodwell Justin R. 
Published: December 2012

AbstractThe secondary metabolites produced by bacterial species serve many clinically useful purposes, and Streptomyces have been an abundant source of such compounds. However, a poor understanding of their regulatory cascades leads to an inability to isolate all of the secondary metabolites this genus is capable of producing. This study focuses on comparing synthetic small molecules that were found to alter the production of secondary metabolites in Streptomyces coelicolor. A survey of these molecules suggests that each has a distinct mechanism of action, and hence, could be used as a unique probe of secondary metabolism. A comparative analysis of two of these molecules, ARC2 and ARC6, confirmed that they modulate secondary metabolites in different ways. In a separate study, ARC2 was shown to give rise to a different phenotype through the inhibition of a target in fatty acid biosynthesis. The results of this study suggest that ARC6 does not have the same target, although it might target the same metabolic system. Furthermore, the results demonstrate that ARC2 and ARC6 act through distinct mechanisms and further suggest that chemical probes can be important tools in enhancing our understanding of secondary metabolism and the streptomycete life cycle.
Numerical and Experimental Study of Catalyst Loading and Body Effects on a Gas‐Liquid Trickle‐Flow Bed
Authors: Salimi M. , Hashemabadi S. H. , Noroozi S. , Heidari A. , Bazmi M. 
Published: December 2012

AbstractThe influence of tortuosity and fluid volume fractions on trickle‐flow bed performance was analyzed. Hydrodynamics of the gas‐liquid downward flow through trickle beds, filled with industrial trilobe catalysts, were investigated experimentally and numerically. The pressure drop and liquid holdup were measured at different gas and liquid velocities and in two different loading methods, namely, sock and dense catalyst loading. The effect of sharp corners on hydrodynamic parameters was considered in a bed with rectangular cross section. The reactor was simulated, considering a three‐phase model, appropriate porosity function, and interfacial forces based on the Eulerian‐Eulerian approach. Computational fluid dynamics (CFD) simulation results for pressure drop and liquid holdup agreed well with experimental data. Finally, the velocity distribution in two types of loading and the effect of bed geometry in CFD results demonstrated that pressure drop and liquid holdup were reduced compared to a cylindrical one due to high voidage at sharp corners.
Biomimetic Synthesis of a Water‐Soluble Conducting Polymer of 3,4‐Ethylene‐dioxythiophene
Authors: Nabid M. R. , Shamsianpour M. , Sedghi R. , Moghaddam A. B. , Asadi S. , Osati S. , Safari N. 
Published: December 2012

AbstractA novel biomimetic route for the synthesis of a water‐soluble poly(3,4‐ethylenedioxithiophene) (PEDT) in the presence of poly(styrene sulfonate) (PSS) and using iron(III)‐tetra(p‐sulfonatophenyl)porphyrin (FeIIITSPP), cobalt(III)‐tetra(p‐sulfonatophenyl)porphyrin (CoIIITSPP), manganese(III)‐tetra(p‐sulfonatophenyl)porphyrin (MnIIITSPP), and copper(II)‐tetra(p‐sulfonatophenyl)porphyrin (CuIITSPP) as effective catalysts is presented. The reactions were performed with different monomer, catalyst, template, and initiator concentrations. The absorbance of the polaron bands at various pH values indicated pH 2 as the best condition for polymerization. Precipitation or salting out was highly dependent on the mentioned factors. The formation of PEDT was confirmed by UV‐Vis and FT‐IR spectroscopy. Cyclic voltammetry proved the convenient electroactivity of the synthesized polymer. The presence of PSS that serves as a charge‐compensating dopant provides processability and water solubility and, in addition, a distinct advantage over similar reactions employing native enzymes due to higher stability and lower cost of the catalysts.
pH‐Dependent Coordination of AgI Ions by Histidine: Experiment, Theory, and a Model for SilE
Authors: Mirolo Laurent , Schmidt Tobias , Eckhardt Sonja , Meuwly Markus , Fromm Katharina M. 
Published: December 2012

AbstractArtificial implants and biomaterials lack the natural defense system of our body and, thus, have to be protected from bacterial adhesion and biofilm formation. In addition to the increasing number of implanted objects, the resistance of bacteria is also an important problem. Silver ions are well‐known for their antimicrobial properties, yet not a lot is known about their mode of action. Silver is expected to interact on many levels, thus the development of silver resistance is very difficult. Nevertheless, some bacteria are able to resist silver, even at higher concentrations. One such defense mechanism of bacteria against heavy‐metal intoxication includes an efflux system. SilE, a periplasmic silver‐binding protein that is involved in this defense mechanism, has been shown to possess numerous histidine functions, which strongly bind to silver atoms, as demonstrated by ourselves previously. Herein, we address the question of how histidine binds to silver ions as a function of pH value. This property is important because the local proton concentration in cells varies. Thus, we solved the crystal structures of histidine–silver complexes at different pH values and also investigated the influence of the amino‐acid configuration. These results were completed by DFT calculations on the binding strength and packing effects and led to the development of a model for the mode of action of SilE.
Surface‐Assisted Laser Desorption/Ionization Mass Spectrometric Detection of Biomolecules by Using Functional Single‐Walled Carbon Nanohorns as the Matrix
Authors: Ma Rongna , Lu Minghua , Ding Lin , Ju Huangxian , Cai Zongwei 
Published: December 2012

AbstractA surface‐assisted laser desorption/ionization time‐of‐flight mass spectrometric (SALDI‐TOF MS) method was developed for the analysis of small biomolecules by using functional single‐walled carbon nanohorns (SWNHs) as matrix. The functional SWNHs could transfer energy to the analyte under laser irradiation for accelerating its desorption and ionization, which led to low matrix effect, avoided fragmentation of the analyte, and provided high salt tolerance. Biomolecules including amino acids, peptides, and fatty acids could successfully be analyzed with about 3‐ and 5‐fold higher signals than those obtained using conventional matrix. By integrating the advantages of SWNHs and the recognition ability of aptamers, a selective approach was proposed for simultaneous capture, enrichment, ionization, and MS detection of adenosine triphosphate (ATP). This method showed a greatly improved detection limit (1.0 μM) for the analysis of ATP in complex biological samples. This newly designed protocol not only opened a new application of SWNHs, but also offered a new technique for selective MS analysis of biomolecules based on aptamer recognition systems.
One‐Pot Sequential Organocatalysis: Highly Stereoselective Synthesis of Trisubstituted Cyclohexanols
Authors: Dai Qipu , Arman Hadi , Zhao John Cong‐Gui 
Published: December 2012

AbstractA highly diastereoselective (d.r. >99:1) and enantioselective (ee value up to 96 %) synthesis of trisubstituted cyclohexanols was achieved by using a one‐pot sequential organocatalysis that involved a quinidine thiourea‐catalyzed tandem Henry–Michael reaction between nitromethane and 7‐oxo‐hept‐5‐en‐1‐als followed by a tetramethyl guanidine (TMG)‐catalyzed tandem retro‐Henry–Henry reaction on the reaction products of the tandem Henry–Michael reaction. Through a mechanistic study, it has also been demonstrated that similar results may also be achieved with this one‐pot sequential organocatalysis by using the racemic Henry product as the substrate.
Fast Track API Manufacturing from Shake Flask to Production Scale Using a 1000‐L Single‐Use Facility
Authors: Minow Benjamin , de Witt Hugo , Knabben Ingo 
Published: December 2012

AbstractA systematic and integrated use of single‐use technologies was combined with a robust monoclonal antibody platform, which led to a substantial reduction of manufacturing costs, reduced timelines and increased flexibility in clinical manufacturing. A direct scale‐up of a high titer monoclonal antibody‐expressing CHO DG44‐based cell culture platform was performed from shake flasks to a 1000 L production scale in a completely single‐use manufacturing facility. The scale‐up was done on the basis of calculating the specific volumetric power input which allowed a direct transfer from small culture volumes to the production scale. The timelines for process development were reduced to 3 months from the Research Cell Bank to the drug substance with highly optimized cells and appropriate culture conditions.
Single‐Use Technologies for Biopharmaceutical Production: Report from the Working Group Bioprocess Technology – Upstream Processing
Authors: Meusel Wolfram , Kauling Jörg , Löffelholz Christian 
Published: December 2012

AbstractThe main goal of the Bioprocess Technology working group is to overcome existing knowledge deficits in the bioprocess characterization of single‐use bioreactors. The required methods have been investigated extensively, evaluated for their suitability for certain single‐use bioreactors, and summarized into a basic structure in the so‐called conceptual matrix. Development of standard operating procedures for the methods selected as well as their verification in interlaboratory tests guarantee that in the future a spectrum of unified and validated methods can be used to compare different bioreactor types objectively.
The Impact of Geology of Recharge Areas on Groundwater Quality: A Case Study of Zhob River Basin, Pakistan
Authors: Umar Muhammad , Waseem Amir , Sabir Muhammad Amjad , Kassi Akhtar Muhammad , Khan Abdul Salam 
Published: December 2012

AbstractGroundwater is a major source of water supply for domestic and irrigation uses in semiarid, remote but rapidly developing Kilasaifullah district part of Zhob River Basin, located at Pakistan–Afghanistan Border. Zhob River is among few major rivers of perennial nature in Balochistan, which flows from WSW to ENE and falls in Gomal River, a tributary of Indus River. Keeping in view the important geopolitical position and rapid development of the region, this study is primarily focused on groundwater chemistry for contamination sources as well as agriculture development. Water samples from open and tube wells are analyzed and calculated for electrical conductivity (EC), total dissolved solids (TDS), turbidity, pH, K+, Na+, Ca2+, Mg2+, HCO, Cl−, NO, SO, PO, sodium percent (Na%), sodium adsorption ratio (SAR), Kelly's index (KI), and heavy metals (Fe, Cu, Cr, Zn, Pb, and Mn). On the basis of the chemical constituents two zones within the study area are identified and possible causes of the contaminants are pointed out. Two recharge areas were responsible for the different chemical results in groundwater, e.g., zone A was recharged from NNW saline geological formations (Nisai, Khojak, Multana, Bostan formations, and Muslim Bagh ophiolites), which are concentrated with high sodium and chloride. On the other hand Zone B was sourced from SSW from carbonate rich rocks (Alozai, Loralai, Parh formations, and Muslim Bagh ophiolites). The groundwater is classified as C2–S1, C3–S1, C3–S2, C4–S2 on the basis of EC and SAR values which indicate that most of the water of both zones can be used for irrigation safely except the samples plotted in C3–S2 and C4–S2 categories which could be dangerous for soil and crops. Groundwater samples are plotted in good to permissible limits with some samples excellent to good and few samples belong to doubtful category based on sodium percent. Groundwater of zone A is unsuitable for irrigation use due to higher values of KI (more than one) but water of zone B are good for irrigation based on KI. In general, water of both zones is suitable for irrigation but care should be taken during the selection of crops which are sensitive to alkalinity or sodium hazards particularly in zone A.