bluuebunny/crossref_metadata_2025 huggingface dataset:
Bio‐Based Hyperbranched Polyurethane Nanocomposites
Authors: Karak Niranjan
Published: June 2015

This article describes bio‐based hyperbranched polyurethane nanocomposites with special emphasis on vegetable oil–based polyurethanes. The article also demonstrates the importance of such nanocomposites and the roles of nanomaterials on ultimate performance of such polymeric materials. Materials and methods for preparation of bio‐based hyperbranched polyurethanes and their nanocomposite are also discussed. Fourier transformed infrared spectroscopic, X‐ray diffraction, thermogravimetric analysis, differential scanning calorimetric, scanning electron microscopic, and transmission electron microscopic studies are briefly mentioned to characterize such nanocomposites. Physicomechanical, chemical, thermal, and biological attributes like biodegradability and biocompatibility of the nanocomposites are also demonstrated in this article. The article shows that the fabrication of appropriate nanocomposites of bio‐based hyperbranched polyurethane using suitable nanomaterials is the key guideline to achieve desired performance or new set of exciting performance for such environmentally benign materials. Finally, the article emphasizes various applications of bio‐based hyperbranched polyurethanes and their nanocomposites.
Polymers Applications in Petroleum Production
Authors: Lucas Elizabete F. , Spinelli Luciana S. , Khalil Carlos N.
Published: June 2015

This article overviews the application of macromolecules in the various exploration and production operations of the petroleum industry. The main molecules utilized are presented as well as those with potential application in different functions, with a description of the operations in which they are used, their action mechanism and preliminary laboratory tests. Aspects related to the solubility of polymer additives are also covered since the polymers are used in liquid media (hydrophilic or hydrophobic), such that they have to be soluble to allow dispersal or suspension, depending on the action mechanism involved in each application. In the end, aspects of toxicity, economics, environmental impact, and occupational health and safety are discussed.
Analytical sensitivity analysis of transient groundwater flow in a bounded model domain using the adjoint method
Authors: Lu Zhiming , Vesselinov Velimir V.
Published: June 2015

Sensitivity analyses are an important component of any modeling exercise. We have developed an analytical methodology based on the adjoint method to compute sensitivities of a state variable (hydraulic head) to model parameters (hydraulic conductivity and storage coefficient) for transient groundwater flow in a confined and randomly heterogeneous aquifer under ambient and pumping conditions. For a special case of two‐dimensional rectangular domains, these sensitivities are represented in terms of the problem configuration (the domain size, boundary configuration, medium properties, pumping schedules and rates, and observation locations and times), and there is no need to actually solve the adjoint equations. As an example, we present analyses of the obtained solution for typical groundwater flow conditions. Analytical solutions allow us to calculate sensitivities efficiently, which can be useful for model‐based analyses such as parameter estimation, data‐worth evaluation, and optimal experimental design related to sampling frequency and locations of observation wells. The analytical approach is not limited to groundwater applications but can be extended to any other mathematical problem with similar governing equations and under similar conceptual conditions.
Chaperones, Chaperonins and Heat‐Shock Proteins
Authors: Consalvi Valerio , Chiaraluce Roberta
Published: June 2015

The protein folding of a nascent polypeptide is the decoding of the linear information contained in the primary sequence into the native and functionally active three‐dimensional conformation. Chaperone proteins and folding catalysts may contribute to successful folding into the native and active protein conformation in the crowded cellular environment, thus avoiding aggregation of non‐native protein forms. Molecular chaperonesin vivoplay a pivotal role in the maintenance of the proteome quality control and in the correct balance between protein folding and degradation. The unbalance of the equilibrium between protein synthesis, protein folding and protein degradation may contribute to protein misfolding and aggregation which may lead to the onset of several degenerative diseases associated with protein aggregation, such as Alzheimer's and Huntington's disease.

Key Concepts

The native protein conformation is the active and functional form of the proteinin vivo.

Protein chaperones assist several proteins in the folding to their native conformation.

Protein chaperones contribute to maintain the correct balance between protein synthesis and degradation.

Chaperones are ubiquitous proteins and are present in all the cells and in all the cellular compartments.

Most of chaperones require adenosine triphosphate for their function.

Chaperones prevent protein misfolding and aggregation that may be associated to several degenerative diseases.
m
RNA
Splicing: Role of sn
RNA
s
Authors: Padgett Richard A
Published: June 2015

Eukaryotic genomes code for many types of non‐coding RNAs (ncRNAs). One class of these ncRNAs is termed small nuclear RNAs (snRNAs). The snRNAs are, in turn, complexed with proteins to form small nuclear ribonucleoprotein particles (snRNPs). Many of these snRNPs are involved in the nuclear maturation of primary transcripts of messenger RNAs (mRNAs). Certain snRNAs are involved in the formation and function of spliceosomes, the large ribonucleoprotein structures in which pre‐mRNA splicing takes place. Most metazoan genomes contain two distinct types of spliceosomes which differ primarily in their snRNA composition. Biochemical, genetic and structural evidences suggest that snRNAs are core components of the catalytic centre of the spliceosomes.

Key Concepts

Eukaryotic genes often contain introns that are removed by RNA splicing.

RNA splicing takes place in large complexes of RNAs and proteins called spliceosomes.

Small nuclear RNAs (snRNAs) are essential parts of spliceosomes.

snRNAs are complexed with proteins to form snRNPs which are recruited to unspliced primary RNA transcripts and direct the formation of spliceosomes.

Evidence is growing that the snRNAs compose much if not all of the active site of the spliceosome suggesting that spliceosomes, like ribosomes, are RNA machines.
Major Histocompatibility Complex (
MHC
): Mouse
Authors: Stuart Patrick M
Published: June 2015

The major histocompatibility complex (MHC) of the mouse, which is called the
H2
complex, is located on chromosome 17. It contains genes critical to the functioning of the immune system, the products of which are intimately involved in the initiation of immune responses. The proteins made by these genes display a significant amount of polymorphism, or sequence variability. Few genes possess this degree of polymorphism, but it is critical to the immune response and to the survival of a species. The chief characteristic of MHC molecules is their ability to bind small peptides. These bound peptides along with specific areas of the MHC molecule are the structures that interact with the T‐cell receptor (TCR) leading to activation of a T‐cell immune response, which in turn can active other cells of immune system. Thus, they determine which TCRs are functional which in turn indicates which peptides a T cell will respond to.

Key Concepts

The historical background and the genetics of MHC development are described.

The expression and function of MHC class I genes is described.

MHC class I molecules are expressed on virtually all nucleated cells and function to present foreign and self‐antigens to the immune system.

MHC class I expression is dependent on peptide binding in the peptide binding groove of the molecule.

MHC class I polymorphism is important for species resistance to infectious disease.

The expression and function of MHC class II genes is described.

MHC class II expression is required for generation and function of CD4 T cells.

Nonclassical class I molecules bind a variety of peptide and nonpeptide antigens that are commonly expressed by pathogenic organisms. .

The function of other genes found within the H2 complex is described.
Life Sciences in Late Antiquity and the Early Middle Ages
Authors: Frampton Michael
Published: June 2015

The life sciences in late antiquity (ad 300–600) and the early Middle Ages (ad 600–1000) centre around the study of three primary categories of ensouled or animate creatures, namely, plants (botany), animals (zoology) and man (anthropology). Major subdisciplines within these general areas of study include pharmacology, medicine, agriculture and veterinary science. The ancient Greek and Roman life scientists of the classical period (600 bc–ad 300) established much of the data and many of the fundamental concepts concerning the nature of the cosmos and its living inhabitants which scholars of the post‐classical period (ad 300–1000) would inherit. The history of the late ancient and the early medieval life sciences is essentially the story of the preservation, dissemination and partial elaboration of classical Graeco‐Roman learning within several very different political, linguistic and religious contexts following the dissolution of the political and cultural synthesis that had been established under the Roman Empire (27 bc–ad 476).

Key Concepts

Life science in the classical (ad 300–600) and post‐classical (ad 600–1000) periods centres around the study of three primary categories of ensouled or animate creatures, plants (botany), animals (zoology) and man (anthropology) and includes the subdisciplines of medicine, pharmacology, agriculture and veterinary science.

Soul (Greekpsyche; Latinanima) is the life principle of plants, animals and people, of which there are three broad species: the vegetative, sensitive and rational.

Classical anatomy, physiology, medicine, botany and zoology are tacitly accepted in the post‐classical period.

The interlocking concepts of (1) teleology, (2) the microcosm–macrocosm analogy and (3) the great chain of being provide common conceptual ground for the ancient (classical) and the late ancient/early medieval (post‐classical) world views.

Classical life science continues to flourish in diverse religious (Jewish, Christian and Muslim) and linguistic (Latin, Greek, Persian, Syriac and Arabic) cultures following the dissolution of the political and cultural synthesis that had been established under the Roman Empire.

Greek, Latin, Syriac and Arabic languages are the primary linguistic vehicles in the diffusion of classical knowledge throughout Europe and the Middle East.

Linguistic barriers are overcome by a handful of multilingual scholars who live on the borderland of two or more dominant cultures.

Christian and Muslim post‐classical scholars use their pagan classical heritage selectively by (1) choosing organisation, conciseness and practicality over theoretical and experimental elaboration and (2) adapting it to the sacred Scriptures of the Judaeo‐Christian (Old and New Testaments) and Muslim (Koranic) cultures.
MicroRNA Signatures as Biomarkers in Cancer
Authors: Adams Brian D , Slack Frank J
Published: June 2015

Microribonucleic acids (miRNAs) are a class of small noncoding RNAs that regulate gene expression posttranscriptionally and control many biological processes including tumourigenesis. Given that, miRNA levels are heavily dysregulated in tumour tissues, many of these RNAs have been identified as classifiers for particular cancer subtypes. In addition, miRNA gene signatures can provide prognostic value, are associated with tumourigenic processes such as metastasis and can identify certain tumour cell types including drug‐resistant and cancer stem cell populations. To gain a better molecular understanding of therapeutic response and disease relapse, there has been an impetus to develop miRNA biomarker profiles through less invasive strategies (i.e. from serum and other sources) rather than from repeated biopsy near the original tumour site. Through these techniques, miRNAs have been found to exist in cell‐free fractions, in exosomes and in circulating tumour cells. While it is still unclear about the mechanisms guiding the release of miRNAs into the serum and other sources, overall, miRNAs have the potential to be used in understanding the pathogenesis of disease prognosis and for diagnostic purposes and in the development of new therapeutic treatment regimens.

Key Concepts

MicroRNAs function as master regulators of gene expression at the posttranscriptional level.

MicroRNAs can function as oncogenes or tumour suppressors in a cell‐context‐dependent manner.

MicroRNAs are stable, found in serum and other biofluids and make good non‐invasive biomarkers.

MicroRNA profiles are associated with therapeutic treatments and disease outcomes.

MicroRNAs can themselves be therapeutic agents or therapeutic targets.
Gas Chromatography and Supercritical Fluid Chromatography with Selective Detection in Pesticide Analysis
Authors: Radović Jagoš R. , Carrasco Pilar B. , Bayona Josep M.
Published: June 2015

Analytical methods based on GC (gas chromatography) and SFC (supercritical fluid chromatography) for the determination of pesticides are presented. Organochlorine, organonophosphorous, pyretroids, phenylureas, sulfonilureas, carbamates, chloracetamides, and triazines are presented. Figures of merit and selected applications of the different methods are reported.
Minimizing Contextual Bias in Forensic Firearms Examinations
Authors: Mattijssen Erwin J.A.T. , Stoel Reinoud D. , Kerkhoff Wim
Published: June 2015

Solutions to cognitive and human factor challenges in forensic science are emerging [Dror, I.E. (2014). Practical solutions to cognitive and human factor challenges in forensic science, Forensic Science Policy & Management 4(3–4), 1–9.], but have not yet been widely communicated let alone applied in practice. Within the discipline of forensic firearms examination, a procedure has been developed and implemented that minimizes the effects of domain‐irrelevant information and maximizes the utilization of domain‐relevant information. This procedure, termedcontext management, is described and for this we distinguish between different types of contextual information that an examiner may come across. Contextual information may come from the trace (Level 1), the reference material (Level 2), the case information (Level 3), and the “base rate” information (Level 4) [Stoel, R., Berger, C., Kerkhoff, W., Mattijssen, E.J.A.T. & Dror, I. (2014). Minimizing Contextual Bias in Forensic Casework, inForensic Science and the Administration of Justice: Critical Issues and Directions, p. 67–86, SAGE.]. By going through the steps of the examination of a typical comparison case (i.e., checking and acceptance of the case, preassessment of the case, comparison of the markings, and peer review and reporting), it is illustrated how and when contextual information may influence the examiners' judgment and how this influence can be minimized by implementing context management.
Child Physical Abuse
Authors: Baxter Michael A. , Lowen Deborah E.
Published: June 2015

Child physical abuse is an all‐too‐common form of child maltreatment, second only to neglect. There are varying definitions of child physical abuse, but the most important point is that a child has sustained tissue injury. This can range from bruises to fractures to life‐threatening or fatal head trauma. Determining the incidence and prevalence of physical abuse is difficult for many reasons; national datasets almost certainly do not provide an accurate picture. There are multiple risk factors for child physical abuse, but children can be abused without any risk factors present. Diagnosing child physical abuse requires a thorough medical assessment including a detailed history, complete physical examination, and often ancillary studies such as labs and radiology studies. Abusive head trauma is the leading cause of death in abused children, and often leads to long‐term neurodevelopmental delays. Physically abused children may have short‐ and long‐term medical and mental health problems as a result of their experiences.
Biologically Templated Nanostructure Assemblies
Authors: Behrens Silke S.
Published: June 2015

Living organisms are able to manufacture a variety of sophisticated inorganic materials with precise control over chemical composition, crystal structure, and shape. Biomolecules offer unique functionalities such as specific recognition capabilities or catalytic activity. On the basis of these recognition capabilities, biological subunits are able to self‐assemble into defined superstructures with unique shapes. Furthermore, they may respond to multiple physical, chemical, or biological stimuli, and therefore provide a potential means for manufacturing nanomachines. However, naturally occurring inorganic materials are typically based on protein scaffolds with inorganic minerals, for example, iron oxide or calcium carbonate, which limits their technical application. Hence, the knowledge of biological concepts, functions, and design features has been exploited for manufacturing new, technologically important, and functional inorganic nanomaterials that have no isomorphous complement in nature.

One major challenge in manufacturing nanostructures by biotemplating has been the need to either modify traditional methodologies derived from chemistry or microelectronics or to develop new synthetic pathways in order to make the material synthesis compatible with the relatively labile biotemplates. Various chemical procedures illustrated by selected examples have been elaborated to direct the nucleation and deposition of inorganic materials (e.g., metals, alloys, or semiconductors) on bioassemblies or to link preformed inorganic building blocks to functional biomolecules. Bioassemblies template complex, multidimensional, and inorganic nanoarchitectures that are typically not available by conventional material synthesis. Recently, the templating ability of natural bioassemblies has been improved by means of genetic engineering. Moreover, it has been demonstrated that the biological functionality of the system may be retained under appropriate conditions, which allows the manufacturing of inorganic nanostructures with motility functions. The use of diverse nanostructured bioassemblies based on both proteins (e.g., cell components such as microtubules, microfilaments, and S‐layers) or microorganisms (i.e., viruses and diatoms) and deoxyribonucleic acid is discussed for their potential of templating of inorganic nanoarchitectures.
Human Metapneumovirus Matrix Protein
Authors: Leyrat Cedric , Renner Max , Grimes Jonathan M
Published: June 2015

The matrix protein (M) of paramyxoviruses plays a key role in determining virion morphology by directing viral assembly and budding. The structure of the human metapneumovirus M was solved by X‐ray crystallography, with two dimers in the asymmetric unit. The structure revealed the presence of a high‐affinity Ca2+binding site. Molecular dynamics simulations in combination with fluorescence‐based thermal shift assays predicted a secondary lower affinity site, located on the same face of the protein. The two binding sites have been shown to stabilize the protein structure, and their conservation across the human pneumoviruses suggests a role for calcium in regulating interactions required for assembly and budding of this subgroup of the paramyxoviruses.
Longitudinal analysis of respiratory outcomes among bauxite exposed workers in western Australia
Authors: Dennekamp Martine , de Klerk Nicholas Hubert , Reid Alison , Abramson Michael John , Cui Jisheng , Del Monaco Anthony , Fritschi Lin , Benke Geza Paul , Sim Malcolm Ross , Musk Arthur William
Published: June 2015

Introduction

Occupational exposure to bauxite is common in the aluminium industry but little is known about the associated health effects. This study investigates respiratory health in relation to respirable bauxite dust exposure longitudinally over a 13 year period.

Methods

An inception cohort study recruited 91 male bauxite miners and 363 male alumina refinery workers. Annual measurements of respiratory symptoms and lung function were made. Cumulative exposure to bauxite was derived from job histories and air monitoring data. Mixed‐effects modeling was used.

Results

No associations were found between cumulative bauxite exposure and respiratory symptoms or lung function. However, when analysis was restricted to the first three rounds, FEV1 was significantly lower in all exposure groups than in those unexposed but with no significant trend.

Conclusion

Increasing exposure to bauxite dust in the aluminum industry was not associated with respiratory symptoms or consistent decrements in lung function. Am. J. Ind. Med. 58:897–904, 2015. © 2015 Wiley Periodicals, Inc.
De novo, heterozygous, loss‐of‐function mutations in SYNGAP1 cause a syndromic form of intellectual disability
Authors: Parker Michael J. , Fryer Alan E. , Shears Deborah J. , Lachlan Katherine L. , McKee Shane A. , Magee Alex C. , Mohammed Shehla , Vasudevan Pradeep C. , Park Soo‐Mi , Benoit Valérie , Lederer Damien , Maystadt Isabelle , study DDD , FitzPatrick David R.
Published: June 2015

De novo mutations (DNM) in SYNGAP1, encoding Ras/Rap GTPase‐activating protein SynGAP, have been reported in individuals with nonsyndromic intellectual disability (ID). We identified 10 previously unreported individuals with SYNGAP1 DNM; seven via the Deciphering Developmental Disorders (DDD) Study, one through clinical analysis for copy number variation and the remaining two (monozygotic twins) via a research multi‐gene panel analysis. Seven of the nine heterozygous mutations are likely to result in loss‐of‐function (3 nonsense; 3 frameshift; 1 whole gene deletion). The remaining two mutations, one of which affected the monozygotic twins, were missense variants. Each individual carrying a DNM in SYNGAP1 had moderate‐to‐severe ID and 7/10 had epilepsy; typically myoclonic seizures, absences or drop attacks. 8/10 had hypotonia, 5/10 had significant constipation, 7/10 had wide‐based/unsteady gait, 3/10 had strabismus, and 2/10 had significant hip dysplasia. A proportion of the affected individuals had a similar, myopathic facial appearance, with broad nasal bridge, relatively long nose and full lower lip vermilion. A distinctive behavioral phenotype was also observed with aggressive/challenging behavior and significant sleep problems being common. 7/10 individuals had MR imaging of the brain each of which was reported as normal. The clinical features of the individuals reported here show significant overlap with those associated with 6p21.3 microdeletions, confirming that haploinsufficiency for SYNGAP1 is responsible for both disorders. © 2015 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.
Synthesis, characterization and catalytic, cytotoxic and antimicrobial activities of two novel cyclotriphosphazene‐based multisite ligands and their Ru(II) complexes
Authors: Erdener Çıralı Diğdem , Uyar Zafer , Koyuncu İsmail , Hacıoğlu Nurcihan
Published: June 2015

Two novel cyclotriphosphazene ligands (2 and 3) bearing 3‐oxypyridine groups and their corresponding Ru(II) complexes (4 and 5) were synthesized and their structures were characterized using Fourier transform infrared, 1H NMR and 31P NMR spectroscopic data and elemental analysis. The Ru(II) complexes were used as catalysts for catalytic transfer hydrogenation of p‐substituted acetophenone derivatives in the presence of KOH. Additionally, the cytotoxic activities of compounds 2, 3, 4, 5 were evaluated against PC3 (human prostate cancer), DLD‐1 (human colorectal cancer), HeLa (human cervical cancer) and PNT1A (normal human prostate) cell lines. Finally the antimicrobial activities of compounds 2, 3, 4, 5 were evaluated against a panel of Gram‐positive and Gram‐negative bacteria and yeast cultures. The complexes showed efficient catalytic activity towards transfer hydrogenation of acetophenone derivatives, especially those bearing electron‐withdrawing substituents on the para‐position of the aryl ring. The compounds were found to have moderate to high cytotoxic and antimicrobial activities, and Ru(II) complexation enhanced both cytotoxic and antimicrobial activities in comparison with the parent compounds. Copyright © 2015 John Wiley & Sons, Ltd.
The Development and Testing of a New Version of the Cognitive Reflection Test Applying Item Response Theory (IRT)
Authors: Primi Caterina , Morsanyi Kinga , Chiesi Francesca , Donati Maria Anna , Hamilton Jayne
Published: June 2015

The cognitive reflection test (CRT) is a short measure of a person's ability to resist intuitive response tendencies and to produce a normatively correct response, which is based on effortful reasoning. Although the CRT is a very popular measure, its psychometric properties have not been extensively investigated. A major limitation of the CRT is the difficulty of the items, which can lead to floor effects in populations other than highly educated adults. The present study aimed at investigating the psychometric properties of the CRT applying item response theory analyses (a two‐parameter logistic model) and at developing a new version of the scale (the CRT‐long), which is appropriate for participants with both lower and higher levels of cognitive reflection. The results demonstrated the good psychometric properties of the original, as well as the new scale. The validity of the new scale was also assessed by measuring correlations with various indicators of intelligence, numeracy, reasoning and decision‐making skills, and thinking dispositions. Moreover, we present evidence for the suitability of the new scale to be used with developmental samples. Finally, by comparing the performance of adolescents and young adults on the CRT and CRT‐long, we report the first investigation into the development of cognitive reflection. Copyright © 2015 John Wiley & Sons, Ltd.
Log‐gamma linear‐mixed effects models for multiple outcomes with application to a longitudinal glaucoma study
Authors: Zhang Peng , Luo Dandan , Li Pengfei , Sharpsten Lucie , Medeiros Felipe A.
Published: June 2015

Glaucoma is a progressive disease due to damage in the optic nerve with associated functional losses. Although the relationship between structural and functional progression in glaucoma is well established, there is disagreement on how this association evolves over time. In addressing this issue, we propose a new class of non‐Gaussian linear‐mixed models to estimate the correlations among subject‐specific effects in multivariate longitudinal studies with a skewed distribution of random effects, to be used in a study of glaucoma. This class provides an efficient estimation of subject‐specific effects by modeling the skewed random effects through the log‐gamma distribution. It also provides more reliable estimates of the correlations between the random effects. To validate the log‐gamma assumption against the usual normality assumption of the random effects, we propose a lack‐of‐fit test using the profile likelihood function of the shape parameter. We apply this method to data from a prospective observation study, the Diagnostic Innovations in Glaucoma Study, to present a statistically significant association between structural and functional change rates that leads to a better understanding of the progression of glaucoma over time.
Investigations into the Biosynthesis, Regulation, and Self‐Resistance of Toxoflavin in Pseudomonas protegens Pf‐5
Authors: Philmus Benjamin , Shaffer Brenda T. , Kidarsa Teresa A. , Yan Qing , Raaijmakers Jos M. , Begley Tadhg P. , Loper Joyce E.
Published: June 2015

Pseudomonas spp. are prolific producers of natural products from many structural classes. Here we show that the soil bacterium Pseudomonas protegens Pf‐5 is capable of producing trace levels of the triazine natural product toxoflavin (1) under microaerobic conditions. We evaluated toxoflavin production by derivatives of Pf‐5 with deletions in specific biosynthesis genes, which led us to propose a revised biosynthetic pathway for toxoflavin that shares the first two steps with riboflavin biosynthesis. We also report that toxM, which is not present in the well‐characterized cluster of Burkholderia glumae, encodes a monooxygenase that degrades toxoflavin. The toxoflavin degradation product of ToxM is identical to that of TflA, the toxoflavin lyase from Paenibacillus polymyxa. Toxoflavin production by P. protegens causes inhibition of several plant‐pathogenic bacteria, and introduction of toxM into the toxoflavin‐sensitive strain Pseudomonas syringae DC3000 results in resistance to toxoflavin.
Structure‐Based Mechanism of Oleate Hydratase from Elizabethkingia meningoseptica
Authors: Engleder Matthias , Pavkov‐Keller Tea , Emmerstorfer Anita , Hromic Altijana , Schrempf Sabine , Steinkellner Georg , Wriessnegger Tamara , Leitner Erich , Strohmeier Gernot A. , Kaluzna Iwona , Mink Daniel , Schürmann Martin , Wallner Silvia , Macheroux Peter , Gruber Karl , Pichler Harald
Published: June 2015

Hydratases provide access to secondary and tertiary alcohols by regio‐ and/or stereospecifically adding water to carbon‐carbon double bonds. Thereby, hydroxy groups are introduced without the need for costly cofactor recycling, and that makes this approach highly interesting on an industrial scale. Here we present the first crystal structure of a recombinant oleate hydratase originating from Elizabethkingia meningoseptica in the presence of flavin adenine dinucleotide (FAD). A structure‐based mutagenesis study targeting active site residues identified E122 and Y241 as crucial for the activation of a water molecule and for protonation of the double bond, respectively. Moreover, we also observed that two‐electron reduction of FAD results in a sevenfold increase in the substrate hydration rate. We propose the first reaction mechanism for this enzyme class that explains the requirement for the flavin cofactor and the involvement of conserved amino acid residues in this regio‐ and stereoselective hydration.
Synthesis, Characterization, and Repair of a Flexible O6‐2′‐Deoxyguanosine‐alkylene‐O6‐2′‐deoxyguanosine Intrastrand Cross‐Link
Authors: O'Flaherty Derek K. , Wilds Christopher J.
Published: June 2015

Oligonucleotides tethered by an alkylene linkage between the O6‐atoms of two consecutive 2′‐deoxyguanosines, which lack a phosphodiester linkage between these residues, have been synthesized as a model system of intrastrand cross‐linked (IaCL) DNA. UV thermal denaturation studies of duplexes formed between these butylene‐ and heptylene‐linked oligonucleotides with their complementary DNA sequences revealed about 20 °C reduction in stability relative to the unmodified duplex. Circular dichroism spectra of the model IaCL duplexes displayed a signature characteristic of B‐form DNA, suggesting minimal global perturbations are induced by the lesion. The model IaCL containing duplexes were investigated as substrates of O6‐alkylguanine DNA alkyltransferase (AGT) proteins from human and E. coli (Ada‐C and OGT). Human AGT was found to repair both model IaCL duplexes with greater efficiency towards the heptylene versus butylene analog adding to our knowledge of substrates this protein can repair.
Design, Synthesis, and Characterization of a Photoactivatable Caged Prodrug of Imatinib
Authors: Zindler Melanie , Pinchuk Boris , Renn Christian , Horbert Rebecca , Döbber Alexander , Peifer Christian
Published: June 2015

Imatinib is the first protein kinase inhibitor approved for clinical use and is a seminal drug for the concept of targeted therapy. Herein we report on the design, synthesis, photokinetic properties, and in vitro enzymatic evaluation of a photoactivatable caged prodrug of imatinib. This approach allows spatial and temporal control over the activation of imatinib triggered by ultraviolet light. The successful application of the photoactivation concept to this significant kinase inhibitor provides further evidence for the caging technique as a feasible approach in the kinase field. The presented photoactivatable imatinib prodrug will be highly useful as a pharmacological tool to study the impact of imatinib toward biological systems in greater detail.
Safety, tolerability, pharmacokinetics, and pharmacodynamic effects of naloxegol at peripheral and central nervous system receptors in healthy male subjects: A single ascending‐dose study
Authors: Eldon Michael A. , Kugler Alan R. , Medve Robert A. , Bui Khanh , Butler Kathleen , Sostek Mark
Published: June 2015

This randomized, double‐blind, placebo‐controlled, ascending‐dose, crossover study evaluated single oral doses of naloxegol (NKTR‐118; 8, 15, 30, 60, 125, 250, 500, and 1000 mg), a PEGylated derivative of naloxone, for safety and tolerability, antagonism of peripheral and central nervous system (CNS) effects of intravenous morphine, and pharmacokinetics. Healthy men were randomized 1:1 to naloxegol or naloxegol‐matching placebo administered with morphine and lactulose in a 2‐period crossover design. Periods were separated by a 5‐ to 7‐day washout. Assessments included safety, tolerability, orocecal transit time (OCTT), pupillary miosis, and pharmacokinetics. The study was completed by 46 subjects. The most common adverse events were somnolence, dizziness, headache, and nausea. Greater reversal of morphine‐induced delay in OCTT occurred with increasing naloxegol dose, demonstrating dose‐ordered antagonism of morphine's peripheral gastrointestinal effects. Forty‐four subjects showed no reversal of pupillary miosis; 2 showed potential partial reversal at 250 and 1000 mg, indicating negligible antagonism of morphine's CNS effects at doses ≤ 125 mg. Rapid absorption, linear pharmacokinetics up to 1000 mg, and low to moderate between‐subject pharmacokinetic variability was observed. The pharmacokinetics of morphine or its glucuronide metabolites were unaltered by concurrent naloxegol administration. Naloxegol was generally safe and well tolerated at single doses up to 1000 mg.
Mesoporous Alumina Nanoparticles as Host Tunnel‐like Pores for Removal and Recovery of Insecticides from Environmental Samples
Authors: Derbalah Aly , El‐Safty Sherif A. , Shenashen Mohamed A. , Abdel Ghany Nabil A.
Published: June 2015

Water contamination with lindane, which is a persistent, toxic, and priority insecticide, is a major problem worldwide. This study presents the fabrication of mesoporous alumina nanoparticles (MA–NPs) with a large surface‐area‐to‐volume ratio, active surface sites, and open channel pores to trap/adsorb insecticide molecules, such as lindane. Key factors, such as temperature, pH (i.e., 4.5), adsorbate–adsorbent concentration, and contact time, influence the thermodynamics and kinetics of heterogeneous lindane–MA–NP adsorption. Results show that the maximum adsorption capacity (qm) of lindane is 25.54 mg g−1 at 20 °C. MA–NPs also exhibits a high uptake efficiency (>80 %) of lindane after 20 cycles, which results in effective regeneration and reusability characteristics. MA–NPs were also applied in real environmental samples from tap and lake water sources contaminated with lindane. The results indicate that the MA–NPs show evidence of their environmental impact, their potential influence on the removal and recovery of lindane, and their possible contribution to waste management.
Application of a Bayesian nonparametric model to derive toxicity estimates based on the response of Antarctic microbial communities to fuel‐contaminated soil
Authors: Arbel Julyan , King Catherine K. , Raymond Ben , Winsley Tristrom , Mengersen Kerrie L.
Published: June 2015

Ecotoxicology is primarily concerned with predicting the effects of toxic substances on the biological components of the ecosystem. In remote, high latitude environments such as Antarctica, where field work is logistically difficult and expensive, and where access to adequate numbers of soil invertebrates is limited and response times of biota are slow, appropriate modeling tools using microbial community responses can be valuable as an alternative to traditional single‐species toxicity tests. In this study, we apply a Bayesian nonparametric model to a soil microbial data set acquired across a hydrocarbon contamination gradient at the site of a fuel spill in Antarctica. We model community change in terms of OTUs (operational taxonomic units) in response to a range of total petroleum hydrocarbon (TPH) concentrations. The Shannon diversity of the microbial community, clustering of OTUs into groups with similar behavior with respect to TPH, and effective concentration values at level x, which represent the TPH concentration that causes x% change in the community, are presented. This model is broadly applicable to other complex data sets with similar data structure and inferential requirements on the response of communities to environmental parameters and stressors.
Posture Control for Personal Mobility Robot Using Feedback Compensation with Unstable Pole
Authors: Hirose Noriaki , Tajima Ryosuke , Sukigara Kazutoshi , Tsusaka Yuji
Published: June 2015

This paper presents a novel posture control approach using feedback compensation with an unstable pole. For a narrow and small personal mobility robot (PMR), this is needed in order to control its posture for achieving quick turning and high acceleration. However, in the conventional control approach that uses the posture angle as a controlled variable, the zero moment point (ZMP) does not settle to the desired point in the following cases: an unknown disturbance force given to the PMR, a fluctuation in the center of gravity of the PMR, and a change in the conditions between the tires and the road surface. In this paper, a novel control method using feedback compensation with an unstable pole is proposed to achieve the desired ZMP in the steady state. The proposed controller changes the control input for the actuator of posture control to zero in order to achieve the desired posture angle. The effectiveness of the proposed approach is verified through experiments using a prototype of the PMR.
Birthday Issues!
Authors: Hindson Karen
Published: June 2015

Editor Karen Hindson congratulates Luis Oro on his 70th birthday and talks about his key role in ChemPubSoc Europe and the journals they own.
Central habituation and distraction alter C‐fibre‐mediated laser‐evoked potential amplitudes
Authors: Hüllemann P. , Shao Y.Q. , Manthey G. , Binder A. , Baron R.
Published: June 2015

Background

Recent studies applied laser‐evoked potentials (LEP) for the analysis of small nerve fibre function and focused on the detection of stable C‐fibre‐mediated potentials (C‐LEPs); high technical requirements were needed. The diagnostic significance is still controversially discussed. So far, only few studies focused on the susceptibility of C‐LEPs to distraction and other influences. We hypothesized that C‐LEPs are altered by habituation processes and distraction.

Methods

Twelve subjects were tested with a C‐fibre laser set‐up (neodymium:yttrium‐aluminium‐perovskite laser with a 10‐mm beam diameter and 10‐ms stimulus time) at the left perioral area. In condition I, the subjects received repetitive painful laser stimuli at the right hand to induce habituation. In condition II, the subjects had to fulfil an auditory discrimination task (where the subjects had to estimate the pitch of different tones on a scale for 20 min). C‐LEPs were retrieved before and after the habituation or distraction paradigm. C‐LEPs were also measured in a control group who was not influenced by laser stimuli or other disturbances during a 23‐min break between the two test sessions.

Results

In both test conditions, there was significant C‐LEP amplitude reduction. The LEP amplitudes of the control group remained unchanged.

Conclusions

In the approach of detecting C‐fibre‐mediated potentials with LEP, future studies should take the high susceptibility to distraction and habituation into account.
Effects of an antidepressant mixture on the brain serotonin and predation behavior of hybrid striped bass
Authors: Bisesi Joseph H. , Sweet Lauren E. , van den Hurk Peter , Klaine Stephen J.
Published: June 2015

Antidepressants have been found in measurable concentrations in final treated wastewater effluent and receiving waters throughout the world. Studies have shown that these concentrations are typically not overtly toxic, but the psychotropic mode of action of these chemicals warrants examination of their behavioral effects. Exposure of hybrid striped bass to the antidepressants fluoxetine or venlafaxine alone has been shown to cause decreased brain serotonin levels and increased time to capture prey at concentrations typically 1 to 2 orders of magnitude higher than environmentally relevant concentrations. In the present study, equally effective doses of fluoxetine and venlafaxine were used to perform a mixture study, using a toxic unit approach to determine whether these antidepressants may act in an additive manner at lower concentrations. The results indicated that mixtures of these antidepressants caused decreased brain serotonin and increased time to capture prey at concentrations lower than reported in previous studies. Low concentration mixtures caused an additive effect on brain serotonin levels and time to capture prey, whereas higher concentrations were less than additive. The results were consistent with the dose addition concept, with higher concentration mixtures potentially saturating the effects on serotonin in the brain. Results from the present study indicate that antidepressants have the potential to be additive on the biochemical and individual scale, which necessitates more robust analysis of antidepressant mixtures and their potential to act together in low concentration scenarios. Environ Toxicol Chem 2016;35:938–945. © 2015 SETAC
Sediment concentrations in run‐off varying with spatial scale in an agricultural subwatershed of the Chinese Loess Plateau
Authors: Zheng Mingguo , Li Runkui , He Jijun
Published: June 2015

Information is scarce on the spatial‐scale effect on sediment concentrations in run‐off. This study addressed this issue within an agricultural subwatershed of the Chinese Loess Plateau, using data observed at a hilltop plot, three nested hillslope plots, two entire‐slope plots (a combination of hillslope and valley side slope) and the subwatershed outlet. Dominated by the splash and sheet erosions, the hilltop plot has a minimum Cae (mean sediment concentration for all recorded events) of 45 kg m−3. Unexpectedly, the high sediment concentrations at the hilltop do not occur at high rainfall intensities or large run‐off events because of the protection of surface soils by relatively thick sheet flows. Because of the emergence of rills, Cae is as high as 310 kg m−3 even on the most upper hillslope. Downslope, both Cae and ESC (extreme large values of recorded sediment concentrations) increase; such a slope length effect attenuates with increasing slope length and event magnitude as a result of insufficient sediment availability associated with rill development. Active mass wastings ensure sufficient sediment supply and thus a spatially invariant Cae (approximately 700 kg m−3) and ESC (approximately 1000 kg m−3) at the scale of the entire slope and subwatershed. Detailed examination shows that most small events experience a decrease in sediment concentrations when moving from the entire slope to the subwatershed, indicating that the spatially invariant sediment concentration is valid only for large run‐off events. This study highlights the control of the spatial scale, which determines the dominant erosional process, on erosional regime. Copyright © 2015 John Wiley & Sons, Ltd.
Impact of aqueous two‐phase system design parameters upon the in situ refolding and recovery of invertase
Authors: Sánchez‐Trasviña Calef , González‐Valdez José , Mayolo‐Deloisa Karla , Rito‐Palomares Marco
Published: June 2015

BACKGROUND

Protein refolding represents the limiting step in the recovery of these molecules from inclusion bodies and from denaturing operations. This raises the need for establishing different methodologies to efficiently recover and refold proteins. Aqueous two‐phase systems (ATPS) besides being a primary recovery operation provide good and affordable physicochemical conditions to refold these molecules.

RESULTS

48 different PEG–potassium phosphate ATPS were tested for the partition and refolding of native and denatured invertase. Invertase in both forms has a partition preference for the bottom salt‐rich phase where the polymer molecular weight and the tie‐line length (TLL) selected for the system play a preponderant role. Refolding percentages of up to 100% can be obtained in the polymer‐rich phase and between 50% and 75% in the bottom phase.

CONCLUSIONS

This study reports the characterization of how the different ATPS design parameters such as polymer molecular weight, tie‐line length (TLL) and volume ratio (VR), influence protein partition and refolding using invertase as the protein model. A PEG 3350 g mol−1, TLL 25.0% w/w and VR = 1.00 system was selected as the best option for denatured invertase recovery and refolding with an enzyme recovery of 60.8% and a refolding percentage of 59.7% in the bottom phase of the system. These findings represent advancements en route to establishing an ATPS operation for the potential in situ recovery and refolding of denatured protein based‐products. © 2015 Society of Chemical Industry
Magnetic susceptibility contrast variations in multiple sclerosis lesions
Authors: Li Xu , Harrison Daniel M. , Liu Hongjun , Jones Craig K. , Oh Jiwon , Calabresi Peter A. , van Zijl Peter C.M.
Published: June 2015

Purpose

Recent magnetic resonance imaging (MRI) studies have revealed heterogeneous magnetic susceptibility contrasts in multiple sclerosis (MS) lesions. Due to its sensitivity to disease‐related iron and myelin changes, magnetic susceptibility‐based measures may better reflect some pathological features of MS lesions. Hence, we sought to characterize MS lesions using combined R2* mapping and quantitative susceptibility mapping (QSM).

Materials and Methods

In all, 306 MS lesions were selected from 24 MS patients who underwent 7T MRI. Maps of R2*, frequency, and quantitative susceptibility were calculated using acquired multiecho gradient echo (GRE) phase data. Lesions were categorized based on their image intensity or their anatomical locations. R2* and susceptibility values were quantified in each lesion based on manually drawn lesion masks and compared between lesion groups showing different contrast patterns. Correlations between R2* and susceptibility were also tested in these lesion groups.

Results

In 38% of selected lesions the frequency map did not show the same contrast pattern as the susceptibility map. While most lesions (93%) showed hypointensity on R2*, the susceptibility contrast in lesions varied, with 40% being isointense and 58% being hyperintense in the lesion core. Significant correlations (r = 0.31, P < 0.001) between R2* and susceptibility were found in susceptibility hyperintense lesions, but not in susceptibility isointense lesions. In addition, a higher proportion (74%) of periventricular lesions was found to be susceptibility hyperintense as compared to subcortical (53%) or juxtacortical (38%) lesions.

Conclusion

Combining R2* and QSM is useful to characterize heterogeneity in MS lesions. J. Magn. Reson. Imaging 2016;43:463–473.