bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of Antisocial and Prosocial Behaviour of Bystanders in Workplace Mobbing
Authors: Mulder Roelie , Pouwelse Mieneke , Lodewijkx Hein , Bos Arjan E. R. , van Dam Karen
Published: August 2015

When will bystanders of workplace mobbing show antisocial or prosocial behaviour toward the victim? Results of a 2 × 2 vignette study (N = 177) suggest that high perceived responsibility of the victim for the onset of the mobbing evokes anger and consequently antisocial bystander behaviour, whereas low perceived responsibility generates sympathy and consequently prosocial bystander behaviour. The results further indicate that bystanders will show more antisocial behaviour and less prosocial behaviour toward the victim when they anticipate stigma by association. The implications of these results for interventions seeking to influence bystanders' behaviour in the context of workplace mobbing and for further research on this bystander behaviour are discussed. Copyright © 2015 John Wiley & Sons, Ltd.
Mechanistic understanding of the nonlinear pharmacokinetics and intersubject variability of simeprevir: A PBPK‐guided drug development approach
Authors: Snoeys J , Beumont M , Monshouwer M , Ouwerkerk‐Mahadevan S
Published: August 2015

Simeprevir, a hepatitis C virus (HCV) NS3/4A protease inhibitor, displays nonlinear pharmacokinetics (PK) at therapeutic doses. Using physiologically based PK modeling, various drug‐drug interactions were simulated with simeprevir as victim drug to identify whether saturation of the predominant metabolic enzyme (CYP3A4) or the active hepatic transporters (organic anion‐transporting polypeptide (OATP)1B1/3) could account for the nonlinear PK. Interactions with ritonavir, a strong CYP3A4 inhibitor that does not affect OATP (at 100 mg dose), erythromycin, a moderate CYP3A4 inhibitor, and efavirenz, a moderate CYP3A inducer that does not affect OATP, demonstrated the involvement of CYP3A4. Interaction studies with low‐dose cyclosporine confirmed the role of OATP. The interplay between hepatic uptake and CYP3A4 metabolism was verified by simulations with rifampicin, a potent CYP3A4 inducer and OATP1B1/3 inhibitor, and maintenance doses of cyclosporine. Saturation of gut and liver metabolism by CYP3A4, and saturation of hepatic uptake by OATP1B1/3, seem to account for the observed nonlinear PK of simeprevir.
Synthesis, Characterization, and Biological Properties of Osmium‐Based Tamoxifen Derivatives – Comparison with Their Homologues in the Iron and Ruthenium Series
Authors: Lee Hui Zhi Shirley , Buriez Olivier , Chau François , Labbé Eric , Ganguly Rakesh , Amatore Christian , Jaouen Gérard , Vessières Anne , Leong Weng Kee , Top Siden
Published: August 2015

Three osmium analogues 3a–3c of hydroxytamoxifen were prepared. The antiproliferative effects of these complexes were measured against two breast cancer cell lines (MCF‐7 and MDA‐MB‐231) and compared with those of their homologues of ferrocene (1a–1c) and ruthenocene (2a–2c). The tamoxifen‐like complexes 2c and 3c derived from osmium and ruthenium show good cytotoxicities against the two cell lines (IC50 values between 2 and 3 μM), albeit lower than those of ferrocifen 1c (IC50 between 0.5 and 0.8 μM). These complexes induce senescence of the cells at low concentration (0.5 μM). The mono‐ and diphenol complexes of osmium and ruthenium show little cytotoxicity against the two cell lines (2a, 2b, 3a, 3b; IC50 ≈ 30 μM), whereas the iron analogues show high cytotoxicity (1a and 1b; IC50 = 0.6–1.1 μM against MDA‐MB‐231). Further studies show that the cytotoxicity of the tamoxifen‐like complexes of ruthenium and osmium is multifactorial and is partly due to the presence of the amino chain. Added to this is an effect of the metal center that could be due to a difference in the rate of formation, solubility, and stability of the corresponding quinone methides or to a difference in the acidity of the phenol protons. This work reveals the differences in the mechanisms of action that exist among the complexes of these three metallocenes. The uniqueness of the ferrocene complexes is underlined, but the cytotoxicity of the tamoxifen‐like complexes of osmium and ruthenium is also demonstrated.
Current status of robotic assisted radical cystectomy with intracorporeal ileal neobladder for bladder cancer
Authors: Fahmy Omar , Asri Khairul , Schwentner Christian , Stenzl Arnulf , Gakis Georgios
Published: August 2015

To investigate the current status and feasibility of robotic neobladder diversion after robotic assisted radical cystectomy. A Medline search was conducted resulting in identification of 423 articles. After exclusion of ineligible studies, 3 case series and 5 case reports were considered with a total number of reported cases of 203. Although robotic intracorporeal neobladder reconstruction is in its starting phase, initial perioperative results seem to be comparable to open series. However, randomized studies are needed to confirm non‐inferiority. J. Surg. Oncol. 2015; 112:427–429. © 2015 Wiley Periodicals, Inc.
Epidemiology and risk factors for faecal extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) carriage derived from residents of seven nursing homes in western Shanghai, China
Authors: ZHAO S.-Y. , ZHANG J. , ZHANG Y.-L. , WANG Y.-C. , XIAO S.-Z. , GU F.-F. , GUO X.-K. , NI Y.-X. , HAN L.-Z.
Published: August 2015

Nursing homes (NHs) have been implicated as significant reservoirs of antibiotic-resistant organisms causing severe infectious disease. We investigated the prevalence and molecular epidemiology of, and risk factors for, faecal carriage of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E). A multicentre cross-sectional study was conducted in seven NHs in Shanghai between March 2014 and May 2014. Antimicrobial susceptibility testing and polymerase chain reaction were used to detect genes coding for ESBLs and carbapenemases. NH records at individual-resident level and facility level were examined for potential risk factors. Four hundred and fifty-seven Enterobacteriaceae isolates were collected of which 183 (46·92%) were colonized by ESBL-E. CTX-M enzymes (198/200, 99%) predominated, with CTX-M-14 (84/200, 42%) the most common types. Two carbapenemase producers harboured blaKPC-2. Resistance rates to carbapenems, TZP, AK, FOS, CL and TGC were low. History of invasive procedures [odds ratio (OR) 2·384, 95% confidence interval (CI) 1·318–4·310, P = 0·004], narrow-spectrum cephalosporins (OR 1·635, 95% CI 1·045–2·558, P = 0·031) and broad-spectrum cephalosporins (OR 3·276, 95% CI 1·278–8·398, P = 0·014) were independently associated with ESBL-E carriage. In conclusion, NH residents have a very high prevalence of faecal carriage of ESBL-E. Continuous and active surveillance is important, as are prudent infection control measures and antibiotic use to prevent and control the spread of these antibiotic-resistant strains.
Subsurface pressure profiling: a novel mathematical paradigm for computing colony pressures on substrate during fungal infections
Authors: Patra Subir , Banerjee Sourav , Terejanu Gabriel , Chanda Anindya
Published: August 2015

Colony expansion is an essential feature of fungal infections. Although mechanisms that regulate hyphal forces on the substrate during expansion have been reported previously, there is a critical need of a methodology that can compute the pressure profiles exerted by fungi on substrates during expansion; this will facilitate the validation of therapeutic efficacy of novel antifungals. Here, we introduce an analytical decoding method based on Biot’s incremental stress model, which was used to map the pressure distribution from an expanding mycelium of a popular plant pathogen, Aspergillus parasiticus. Using our recently developed Quantitative acoustic contrast tomography (Q-ACT) we detected that the mycelial growth on the solid agar created multiple surface and subsurface wrinkles with varying wavelengths across the depth of substrate that were computable with acousto-ultrasonic waves between 50 MHz–175 MHz. We derive here the fundamental correlation between these wrinkle wavelengths and the pressure distribution on the colony subsurface. Using our correlation we show that A. parasiticus can exert pressure as high as 300 KPa on the surface of a standard agar growth medium. The study provides a novel mathematical foundation for quantifying fungal pressures on substrate during hyphal invasions under normal and pathophysiological growth conditions.
Seven weeks of Western diet in apolipoprotein-E-deficient mice induce metabolic syndrome and non-alcoholic steatohepatitis with liver fibrosis
Authors: Schierwagen Robert , Maybüchen Lara , Zimmer Sebastian , Hittatiya Kanishka , Bäck Christer , Klein Sabine , Uschner Frank E. , Reul Winfried , Boor Peter , Nickenig Georg , Strassburg Christian P. , Trautwein Christian , Plat Jogchum , Lütjohann Dieter , Sauerbruch Tilman , Tacke Frank , Trebicka Jonel
Published: August 2015

Non-alcoholic steatohepatitis (NASH) is characterised by hepatic steatosis, inflammation and fibrosis, which might progress to cirrhosis. Human NASH is associated with metabolic syndrome (MS). Currently, rodent NASH models either lack significant fibrosis or MS. ApoE−/− mice are a MS model used in cardiovascular research. The aim of this work was to establish and characterise a novel mouse NASH model with significant fibrosis and MS. ApoE−/− and wild-type mice (wt) were fed either a western-diet (WD), methionine-choline-deficient-diet (MCD) or normal chow. Liver histology, RT-PCR, hepatic hydroxyproline content, triglycerides and cholesterol levels and fasting glucose levels assessed hepatic steatosis, inflammation and fibrosis. Further, portal pressure was measured invasively and kidney pathology was assessed by histology. ApoE−/− mice receiving WD showed abnormal glucose tolerance, hepatomegaly, weight gain and full spectrum of NASH including hepatic steatosis, fibrosis and inflammation, with no sign of renal damage. MCD-animals showed less severe liver fibrosis, but detectable renal pathological changes, besides weight loss and unchanged glucose tolerance. This study describes a murine NASH model with distinct hepatic steatosis, inflammation and fibrosis, without renal pathology. ApoE−/− mice receiving WD represent a novel and fast model with all characteristic features of NASH and MS well suitable for NASH research.
A one-step chemiluminescence immunoassay for 20 fluoroquinolone residues in fish and shrimp based on a single chain Fv–alkaline phosphatase fusion protein
Authors: Yu Xuezhi , Tao Xiaoqi , Shen Jianzhong , Zhang Suxia , Cao Xingyuan , Chen Min , Wang Wenjun , Wang Zhanhui , Wen Kai
Published: August 2015

A simple and rapid chemiluminescence competitive direct enzyme-linked generic immunosorbent assay was developed for 20 FQs in fish and shrimp samples.
Easy protocol for making a good E-sinapinic acid matrix for neutral and sulfated carbohydrate MALDI-MS analysis
Authors: Salum María L. , Schmidt De León Tobias , Erra-Balsells Rosa
Published: August 2015

A Z- + E- mixture of cinnamics was prepared in a solution of commercial E-acid (i.e., E-SA) by photoisomerization. This “photo-made at home” MALDI matrix provides direct, rapid and sensitive detection of neutral and sulfated carbohydrates.
Probing structural patterns of ion association and solvation in mixtures of imidazolium ionic liquids with acetonitrile by means of relative1H and13C NMR chemical shifts
Authors: Marekha Bogdan A. , Kalugin Oleg N. , Bria Marc , Idrissi Abdenacer
Published: August 2015

Competition between ion solvation and association in mixtures of imidazolium ionic liquids and molecular solvents can be systematically addressed by the analysis of relative chemical shift variation with mixture composition.
Synthesis and structure–activity relationships for cytotoxicity and apoptosis-inducing activity of (+)-halichonine B
Authors: Hayakawa Ichiro , Nakamura Tomomi , Ohno Osamu , Suenaga Kiyotake , Kigoshi Hideo
Published: August 2015

(+)-Halichonine B and its analogues were synthesized, and their biological activities were evaluated. It was revealed that the secondary amino groups in the side chain portion are important for the strong cytotoxicity of halichonine B and that the N11-prenyl group is unimportant.
A fixable supramolecular cyclic polymer based on the cucurbit[8]uril-stabilized π–π interaction
Authors: Ji Zhongwei , Li Yipeng , Ding Yu , Chen Guosong , Jiang Ming
Published: August 2015

A novel reversible unimolecular cyclization method based on the CB[8]-stabilized interaction in an aqueous environment has been investigated.
Amide-bridged ladder poly(p-phenylene): synthesis by direct arylation and π-stacked assembly
Authors: Takagi K. , Kato R. , Yamamoto S. , Masu H.
Published: August 2015

Amide-bridged ladder poly(p-phenylene) was synthesized in two steps, through the polycondensation of aromatic diamines and dicarboxylic acid derivatives followed by palladium-catalyzed intramolecular direct arylation.
Facile and green aerosol-assisted synthesis of zeolites
Authors: Guo Zhendong , Xiong Guang , liu Liping , Yin Jinpeng , Zhao Ruixue , Yu Shiqiang
Published: August 2015

A facile and green aerosol-assisted method was proposed to synthesize various zeolites.
Binder-free Co–CoOx nanowire arrays for lithium ion batteries with excellent rate capability and ultra-long cycle life
Authors: Zhan Liang , Wang Suqing , Ding Liang-Xin , Li Zhong , Wang Haihui
Published: August 2015

The introduction of metallic Co into the CoOx nanowire array greatly improves the cycle stability and rate capability of the array electrode.
Cu–Ag core–shell nanowires for electronic skin with a petal molded microstructure
Authors: Wei Yong , Chen Song , Lin Yong , Yang Zimei , Liu Lan
Published: August 2015

Cu–Ag core–shell nanowires with excellent oxidation resistance are fabricated and are used as conductive fillers for e-skin with a petal molded micro-structure.
Evidence in favour of ancient octaploidy in the vertebrate genome
Authors: Gibson T.J. , Spring J.
Published: August 2015

Vertebrate genomes are larger than invertebrates and show evidence of extensive gene duplication, including many collinear chromosomal segments. On the basis of this intra-genomic synteny, it has been proposed that two rounds of whole genome duplication (octaploidy) occurred early in the vertebrate lineage. Recently, this early vertebrate octaploidy has been challenged on the basis of gene trees. We report new linkage groups encompassing the matrilin (MATN), syndecan (SDC), Eyes Absent (EYA), HCK kinase and SRC kinase paralogous gene quartets. In contrast to other studies, the sequence trees are weakly supportive of ancient octaploidy. It is concluded that there is no strong evidence against the octaploidy, provided that consecutive genome duplication was rapid.
Insulin and cognitive function in humans: experimental data and therapeutic considerations
Authors: Strachan M.W.J.
Published: August 2015

Data from experimental studies in animals and from epidemiological studies in humans suggest a link between insulin and cognitive performance. Do these results translate into clinical and therapeutic benefit for people with cognitive impairment? Insulin injected peripherally can readily cross the blood–brain barrier. Intravenous insulin can improve aspects of cognitive function in healthy adults and in individuals with Alzheimer's dementia. Moreover, intravenous insulin increases concentrations of a long form of β-amyloid protein, Aβ42. One potential confounding factor with these data, however, is the need for co-administration of glucose with the insulin to maintain euglycaemia as glucose itself can facilitate memory function. Administration of insulin via the intranasal route is scientifically (and therapeutically) more attractive because the insulin goes directly to the cerebrospinal fluid, with minimal systemic absorption; this obviates the need for a glucose infusion. Intranasal insulin may improve some aspects of memory in healthy individuals, but has yet to be studied in people with cognitive impairment. TZDs (thiazolidinediones) reduce peripheral insulin concentrations by enhancing insulin sensitivity. In adults with Type II (non-insulin-dependent) diabetes, TZD therapy improves memory function, but so does sulphonylurea therapy (which elevates peripheral insulin concentrations). Improved memory is linked to lower blood glucose concentrations, rather than altered insulin levels. However, major trials are currently under way examining the impact of TZDs in people with dementia.
The contributions of biosynthesis and acyl chain remodelling to the molecular species profile of phosphatidylcholine in yeast
Authors: Boumann H.A. , de Kroon A.I.P.M.
Published: August 2015

Phosphatidylcholine (PC) is a very abundant membrane lipid in most eukaryotes, including yeast. The molecular species profile of PC, i.e. the ensemble of PC molecules with acyl chains differing in number of carbon atoms and double bonds, is important for membrane function. Pathways of PC synthesis and turnover maintain PC homoeostasis and determine the molecular species profile of PC. Studies addressing the processes involved in establishing the molecular species composition of PC in yeast using stable isotope labelling combined with detection by MS are reviewed.
Membrane traffic in cytokinesis
Authors: Matheson J. , Yu X. , Fielding A.B. , Gould G.W.
Published: August 2015

A crucial facet of mammalian cell division is the separation of two daughter cells by a process known as cytokinesis. An early event in cytokinesis is the formation of an actomyosis contractile ring, which functions like a purse string in the constriction of the forming furrow between the cells. Far less well characterized are the membrane-trafficking steps which deliver new membrane to the cell surface during the plasma membrane expansion known to accompany furrow formation. It is now clearly established that the plasma membrane at the cleavage furrow of mammalian cells has a distinct lipid and protein composition from the rest of the plasma membrane. This may reflect a requirement for both increased surface area during furrowing and for the co-ordinated delivery of intracellular signalling or membrane re-modelling activities to the correct spatial coordinates during cleavage. In this review, we discuss recent work within the area of membrane traffic and cytokinesis.
Cell signalling by oxidized lipids and the role of reactive oxygen species in the endothelium
Authors: Zmijewski J.W. , Landar A. , Watanabe N. , Dickinson D.A. , Noguchi N. , Darley-Usmar V.M.
Published: August 2015

The controlled formation of ROS (reactive oxygen species) and RNS (reactive nitrogen species) is now known to be critical in cellular redox signalling. As with the more familiar phosphorylation-dependent signal transduction pathways, control of protein function is mediated by the post-translational modification at specific amino acid residues, notably thiols. Two important classes of oxidant-derived signalling molecules are the lipid oxidation products, including those with electrophilic reactive centres, and decomposition products such as lysoPC (lysophosphatidylcholine). The mechanisms can be direct in the case of electrophiles, as they can modify signalling proteins by post-translational modification of thiols. In the case of lysoPC, it appears that secondary generation of ROS/RNS, dependent on intracellular calcium fluxes, can cause the secondary induction of H2O2 in the cell. In either case, the intracellular source of ROS/RNS has not been defined. In this respect, the mitochondrion is particularly interesting since it is now becoming apparent that the formation of superoxide from the respiratory chain can play an important role in cell signalling, and oxidized lipids can stimulate ROS formation from an undefined source. In this short overview, we describe recent experiments that suggest that the cell signalling mediated by lipid oxidation products involves their interaction with mitochondria. The implications of these results for our understanding of adaptation and the response to stress in cardiovascular disease are discussed.
Metabolic flux distribution analysis by 13C-tracer experiments using the Markov chain–Monte Carlo method
Authors: Yang J. , Wongsa S. , Kadirkamanathan V. , Billings S.A. , Wright P.C.
Published: August 2015

Metabolic flux analysis using 13C-tracer experiments is an important tool in metabolic engineering since intracellular fluxes are non-measurable quantities in vivo. Current metabolic flux analysis approaches are fully based on stoichiometric constraints and carbon atom balances, where the over-determined system is iteratively solved by a parameter estimation approach. However, the unavoidable measurement noises involved in the fractional enrichment data obtained by 13C-enrichment experiment and the possible existence of unknown pathways prevent a simple parameter estimation method for intracellular flux quantification. The MCMC (Markov chain–Monte Carlo) method, which obtains intracellular flux distributions through delicately constructed Markov chains, is shown to be an effective approach for deep understanding of the intracellular metabolic network. Its application is illustrated through the simulation of an example metabolic network.
Unique features of selenocysteine incorporation function within the context of general eukaryotic translational processes
Authors: Small-Howard A.L. , Berry M.J.
Published: August 2015

Unlike other essential dietary trace elements, selenium exerts its biological actions through its direct incorporation into selenoproteins, as a part of the 21st amino acid, selenocysteine. Fundamental studies have elucidated the unique structures and putative functions of multiple co-translational factors required for the incorporation of selenocysteine into selenoproteins. The current challenge is to understand how these selenocysteine incorporation factors function within the framework of translation. In eukaryotes, co-ordinating nuclear transcription with cytoplasmic translation of genes is a challenge involving complex spatial and temporal regulation. Selenoproteins utilize the common cellular machinery required for synthesis of non-selenoproteins. This machinery includes the elements involved in transcription, mRNA splicing and transport, and translational processes. Many investigators have emphasized the differences between the expression of selenoproteins and other eukaryotic proteins, whereas this review will attempt to highlight common themes and point out where additional interactions may be discovered.
Amazing grass: developmental genetics of maize domestication
Authors: Vollbrecht E. , Sigmon B.
Published: August 2015

Crop plants were domesticated by prehistoric farmers through artificial selection to provide a means of feeding the human population. This article discusses the developmental genetics of crop domestication and improvement, including the historical framework and recent approaches in maize and other grasses. In many cases, selecting for a plant form that correlates with productivity involves controlling meristem activity. In the domestication of modern maize from its progenitor Zea mays ssp. parviglumis, QTL (quantitative trait loci) mapping, genetics and population genomics approaches have identified several genes that contain signatures of selection. Only a few genes involved in the derivation of the highly productive maize ear have been identified, including teosinte glume architecture1 and ramosa1. Future prospects hinge on forward and reverse genetics, as well as on other approaches from the developing discipline of evo-devo (evolutionary developmental biology).
Understanding enzyme action at solid surfaces
Authors: Halling P.J.
Published: August 2015

In solid-phase synthesis, there is interest in using enzymes that normally act on dissolved substrates. It is normally observed that rates and yields are substantially reduced when the usual substrates are covalently attached to a solid particle. Recently, there has been some progress in understanding the reasons for this, and hence how to improve behaviour. Diffusion of enzyme molecules into some of the support particles used in solid-phase chemistry is slow or absent. Methods are now available to visualize the sites of reaction, and hence detect this problem, and identify better support materials. Chemical equilibrium positions for reactions at the surface can be substantially altered compared with those in solution, so may unexpectedly limit yields. The shift can also be exploited to carry out, for example, direct synthesis of peptide bonds in an aqueous environment. The rate of enzyme attack depends on how the substrate moiety is attached to the surface, with an optimal ‘spacer’ length.
Crystallizing membrane proteins for structure–function studies using lipidic mesophases
Authors: Caffrey Martin
Published: August 2015

The lipidic cubic phase method for crystallizing membrane proteins has posted some high-profile successes recently. This is especially true in the area of G-protein-coupled receptors, with six new crystallographic structures emerging in the last 3½ years. Slowly, it is becoming an accepted method with a proven record and convincing generality. However, it is not a method that is used in every membrane structural biology laboratory and that is unfortunate. The reluctance in adopting it is attributable, in part, to the anticipated difficulties associated with handling the sticky viscous cubic mesophase in which crystals grow. Harvesting and collecting diffraction data with the mesophase-grown crystals is also viewed with some trepidation. It is acknowledged that there are challenges associated with the method. However, over the years, we have worked to make the method user-friendly. To this end, tools for handling the mesophase in the pico- to nano-litre volume range have been developed for efficient crystallization screening in manual and robotic modes. Glass crystallization plates have been built that provide unparalleled optical quality and sensitivity to nascent crystals. Lipid and precipitant screens have been implemented for a more rational approach to crystallogenesis, such that the method can now be applied to a wide variety of membrane protein types and sizes. In the present article, these assorted advances are outlined, along with a summary of the membrane proteins that have yielded to the method. The challenges that must be overcome to develop the method further are described.
Unravelling the folding and stability of an ABC (ATP-binding cassette) transporter
Authors: DiBartolo Natalie , Booth Paula J.
Published: August 2015

Prokaryotic importers from the large family of ABC (ATP-binding cassette) transporters comprise four separate subunits: two membrane-embedded and two cytoplasmic ATP-binding subunits. This modular construction makes them ideal candidates for studies of the intersubunit interactions of membrane protein complexes that contain both hydrophobic and hydrophilic subunits. In the present paper, we focus on the vitamin B12 importer of Escherichia coli, BtuCD, that contains two transmembrane BtuC subunits and two ATP-binding BtuD subunits. We have studied the factors that induce subunit dissociation and unfolding in vitro. The BtuCD complex remains intact in alcohol and mild detergents, but urea or SDS separate the BtuC and BtuD subunits, with 6 M urea causing 80% of BtuD to be removed from BtuCD. ATP is found to stabilize the complex as a result of its binding to the BtuD subunits. In the absence of ATP, low concentrations of urea (0.5–3 M) also induce some unfolding, with approximately 14% reduction in helicity in 3 M urea, whereas, in the presence of ATP, no changes are observed. Disassembly at the BtuD–BtuD dimeric interface in BtuCD can be achieved with smaller concentrations of urea (0.5–3 M) than that required to cause disassembly at the BtuC–BtuD transmission interface (3–8 M), suggesting a stronger interaction of the latter. The results also suggest that unfolding and disassociation of subunits appear to be coupled processes. Our work provides insights into the subunit interactions of an ABC transporter and lays the foundation for studies of the reassembly of BtuCD.
A diversity of SERCA Ca2+ pump inhibitors
Authors: Michelangeli Francesco , East J. Malcolm
Published: August 2015

The SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) is probably the most extensively studied membrane protein transporter. There is a vast array of diverse inhibitors for the Ca2+ pump, and many have proved significant in helping to elucidate both the mechanism of transport and gaining conformational structures. Some SERCA inhibitors such as thapsigargin have been used extensively as pharmacological tools to probe the roles of Ca2+ stores in Ca2+ signalling processes. Furthermore, some inhibitors have been implicated in the cause of diseases associated with endocrine disruption by environmental pollutants, whereas others are being developed as potential anticancer agents. The present review therefore aims to highlight some of the wide range of chemically diverse inhibitors that are known, their mechanisms of action and their binding location on the Ca2+ ATPase. Additionally, some ideas for the future development of more useful isoform-specific inhibitors and anticancer drugs are presented.
Chaperone-mediated autophagy: dedicated saviour and unfortunate victim in the neurodegeneration arena
Authors: Schneider Jaime L. , Cuervo Ana Maria
Published: August 2015

The importance of cellular quality-control systems in the maintenance of neuronal homoeostasis and in the defence against neurodegeneration is well recognized. Chaperones and proteolytic systems, the main components of these cellular surveillance mechanisms, are key in the fight against the proteotoxicity that is often associated with severe neurodegenerative diseases. However, in recent years, a new theme has emerged which suggests that components of protein quality-control pathways are often targets of the toxic effects of pathogenic proteins and that their failure to function properly contributes to pathogenesis and disease progression. In the present mini-review, we describe this dual role as ‘saviour’ and ‘victim’ in the context of neurodegeneration for chaperone-mediated autophagy, a cellular pathway involved in the selective degradation of cytosolic proteins in lysosomes.
Lysosome and calcium dysregulation in Alzheimer's disease: partners in crime
Authors: McBrayer MaryKate , Nixon Ralph A.
Published: August 2015

Early-onset FAD (familial Alzheimer's disease) is caused by mutations of PS1 (presenilin 1), PS2 (presenilin 2) and APP (amyloid precursor protein). Beyond the effects of PS1 mutations on proteolytic functions of the γ-secretase complex, mutant or deficient PS1 disrupts lysosomal function and Ca2+ homoeostasis, both of which are considered strong pathogenic factors in FAD. Loss of PS1 function compromises assembly and proton-pumping activity of the vacuolar-ATPase on lysosomes, leading to defective lysosomal acidification and marked impairment of autophagy. Additional dysregulation of cellular Ca2+ by mutant PS1 in FAD has been ascribed to altered ion channels in the endoplasmic reticulum; however, rich stores of Ca2+ in lysosomes are also abnormally released in PS1-deficient cells secondary to the lysosomal acidification defect. The resultant rise in cytosolic Ca2+ activates Ca2+-dependent enzymes, contributing substantially to calpain overactivation that is a final common pathway leading to neurofibrillary degeneration in all forms of AD (Alzheimer's disease). In the present review, we discuss the close inter-relationships among deficits of lysosomal function, autophagy and Ca2+ homoeostasis as a pathogenic process in PS1-related FAD and their relevance to sporadic AD.
Biochemical properties of the kinase PINK1 as sensor protein for mitochondrial damage signalling
Authors: Rüb Cornelia , Schröder Nadja , Voos Wolfgang
Published: August 2015

Defects of mitochondrial functions have been implicated in many different human diseases, in particular neurodegenerative diseases. The kinase PINK1 [phosphatase and tensin homologue (PTEN)-induced kinase 1] has been identified as a crucial player in a specific damage signalling pathway, eliminating defective mitochondria by an autophagic process. Mutations in PINK1 have been shown to cause familial cases of Parkinson's disease. In this review, we summarize the biochemical mechanisms that underlie the association of PINK1 with mitochondria under normal and pathological conditions. This unconventional mitochondrial localization pathway is discussed in the context of the role of PINK1 as a sensor of mitochondrial damage and a causative factor in Parkinson's disease.
Temporal Approach to Removal of a Large Orbital Foreign Body
Authors: de Morais Hécio Henrique Araújo , Barbalho Jimmy Charles Melo , de Souza Dias TasianaGuedes , Grempel RafaelGrotta , de Holanda Vasconcellos Ricardo José
Published: August 2015

Accidents with firearms can result in extensive orbital trauma. Moreover, gun parts can come loose and impale the maxillofacial region. These injuries can cause the loss of visual acuity and impair eye movements. Multidisciplinary treatment is required for injuries associated with this type of trauma. Computed tomography with three-dimensional reconstruction is useful for determining the precise location and size of the object lodged in the facial skeleton, thereby facilitating the planning of the correct surgical approach. The temporal approach is a fast, simple technique with few complications that is indicated for access to the infratemporal fossa. This article describes the use of the temporal approach on a firearm victim in whom the breech of a rifle had impaled orbital region, with the extremity lodged in the infratemporal fossa.
Random bursts determine dynamics of active filaments
Authors: Weber Christoph A. , Suzuki Ryo , Schaller Volker , Aranson Igor S. , Bausch Andreas R. , Frey Erwin
Published: August 2015

Significance

Biological active systems like swimming bacteria or molecular motors in the cell cytoskeleton consume energy locally to create movements or stresses. Although the surrounding fluid gives rise to thermal fluctuations of the system’s dynamic variables, the corresponding statistics can deviate significantly from a thermal Boltzmann distribution. To quantify these differences, we compare the statistics and dynamics of actin filaments driven by molecular motors with Brownian filaments. In both cases, energy injection is local and random; however, for active filaments, motors can generate sudden jump-like changes in the system’s dynamic variables, leading to nonequilibrium energy dissipation. Motor activity results in a nonthermal distribution of filament curvatures and a faster relaxation of filament bends than in the thermal case.
Homotopy principles for equivariant isomorphisms
Authors: Kutzschebauch Frank , Lárusson Finnur , Schwarz Gerald
Published: August 2015

Let

G
G

be a reductive complex Lie group acting holomorphically on Stein manifolds

X
X

and

Y
Y

. Let

p
X

:
X
→

Q
X

p_X\colon X\to Q_X

and

p
Y

:
Y
→

Q
Y

p_Y\colon Y\to Q_Y

be the quotient mappings. When is there an equivariant biholomorphism of

X
X

and

Y
Y

? A necessary condition is that the categorical quotients

Q
X

Q_X

and

Q
Y

Q_Y

are biholomorphic and that the biholomorphism

φ
\varphi

sends the Luna strata of

Q
X

Q_X

isomorphically onto the corresponding Luna strata of

Q
Y

Q_Y

. Fix

φ
\varphi

. We demonstrate two homotopy principles in this situation. The first result says that if there is a

G
G

-diffeomorphism

Φ
:
X
→
Y

\Phi \colon X\to Y

, inducing

φ
\varphi

, which is

G
G

-biholomorphic on the reduced fibres of the quotient mappings, then

Φ
\Phi

is homotopic, through

G
G

-diffeomorphisms satisfying the same conditions, to a

G
G

-equivariant biholomorphism from

X
X

to

Y
Y

. The second result roughly says that if we have a

G
G

-homeomorphism

Φ
:
X
→
Y

\Phi \colon X\to Y

which induces a continuous family of

G
G

-equivariant biholomorphisms of the fibres

p
X

−
1

(
q
)

p_X{^{-1}}(q)

and

p
Y

−
1

(
φ
(
q
)
)

p_Y{^{-1}}(\varphi (q))

for

q
∈

Q
X

q\in Q_X

and if

X
X

satisfies an auxiliary property (which holds for most

X
X

), then

Φ
\Phi

is homotopic, through

G
G

-homeomorphisms satisfying the same conditions, to a

G
G

-equivariant biholomorphism from

X
X

to

Y
Y

. Our results improve upon those of our earlier paper [J. Reine Angew. Math. 706 (2015), 193–214] and use new ideas and techniques.
Historical data as a baseline for conservation: reconstructing long-term faunal extinction dynamics in Late Imperial–modern China
Authors: Turvey Samuel T. , Crees Jennifer J. , Di Fonzo Martina M. I.
Published: August 2015

Extinction events typically represent extended processes of decline that cannot be reconstructed using short-term studies. Long-term archives are necessary to determine past baselines and the extent of human-caused biodiversity change, but the capacity of historical datasets to provide predictive power for conservation must be assessed within a robust analytical framework. Local Chinese gazetteers represent a more than 400-year country-level dataset containing abundant information on past environmental conditions and include extensive records of gibbons, which have a restricted present-day distribution but formerly occurred across much of China. Gibbons show pre-twentieth century range contraction, with significant fragmentation by the mid-eighteenth century and population loss escalating in the late nineteenth century. Isolated gibbon populations persisted for about 40 years before local extinction. Populations persisted for longer at higher elevations, and disappeared earlier from northern and eastern regions, with the biogeography of population loss consistent with the contagion model of range collapse in response to human demographic expansion spreading directionally across China. The long-term Chinese historical record can track extinction events and human interactions with the environment across much longer timescales than are usually addressed in ecology, contributing novel baselines for conservation and an increased understanding of extinction dynamics and species vulnerability or resilience to human pressures.
A free boundary approach to shape optimization problems
Authors: Bucur D. , Velichkov B.
Published: August 2015

The analysis of shape optimization problems involving the spectrum of the Laplace operator, such as isoperimetric inequalities, has known in recent years a series of interesting developments essentially as a consequence of the infusion of free boundary techniques. The main focus of this paper is to show how the analysis of a general shape optimization problem of spectral type can be reduced to the analysis of particular free boundary problems. In this survey article, we give an overview of some very recent technical tools, the so-called shape sub- and supersolutions, and show how to use them for the minimization of spectral functionals involving the eigenvalues of the Dirichlet Laplacian, under a volume constraint.
Third generation behavioural therapy for neurodevelopmental disorders: review and trajectories
Authors: Leoni Mauro , Corti Serafino , Cavagnola Roberto
Published: August 2015

Purpose

– The purpose of this paper is mainly to present a general review of third generation cognitive-behavioural therapies (CBTs), and to debate whether these approaches are applicable to persons with neurodevelopmental disorders (NDD).

Design/methodology/approach

– Despite the lack of consistent literature focused on this population, the authors have considered the available general literature on the third generation of CBTs and analysed core issues of the processes within the context of intellectual disabilities and Autism spectrum disorder.

Findings

– The evidence from typical developing population studies and the emerging literature specific to people with NDD is convincing, but there is a need for studies exploring how and when these therapeutic approaches can be applicable. Two behavioural approaches of third generation therapies – acceptance and commitment therapy and mindfulness-based CBT – appear to have the most potential to be adapted for robust intervention for the broad spectrum of persons with NDD.

Research limitations/implications

– The number of studies and methodologies applied are a clear limitation and the present paper is only exploratory.

Originality/value

– The paper supports clinicians to use the emerging protocols, and to replicate and implement procedures and techniques.
Effect fracture resistance on retardation of crack growth
Authors: Behal Jirí , Homola Petr , Ružek Roman
Published: August 2015

Purpose

– The prediction of fatigue crack growth behaviour is an important part of damage tolerance analyses. Recently, the author’s work has focused on evaluating the FASTRAN retardation model. This model is implemented in the AFGROW code, which allows different retardation models to be compared. The primary advantage of the model is that all input parameters, including those for an initial plane-strain state and its transition to a plane-stress-state, are objectively measured using standard middle-crack-tension M(T) specimens. The purpose of this paper is to evaluate the ability of the FASTRAN model to predict correct retardation effects due to high loading peaks that occur during variable amplitude loading in sequences representative of an aircraft service.

Design/methodology/approach

– This paper addresses pre-setting of the fracture toughness K

R
(based on J-integral J

Q
according to ASTM1820) in the FASTRAN retardation model. A set of experiments were performed using specimens made from a 7475-T7351 aluminium alloy plate. Loading sequences with peaks ordered in ascending-descending blocks were used. The effect of truncating and clipping selected load levels on crack propagation behaviour was evaluated using both experimental data and numerical analyses. The findings were supported by the results of a fractographic analysis.

Findings

– Fatigue crack propagation data defined using M(T) specimens made from Al 7475-T7351 alloy indicate the difficulty of evaluating the following two events simultaneously: fatigue crack increments after application of loads with maximum amplitudes that exceeded J

Q
and subcritical crack increments caused by loads at high stress intensity factors. An effect of overloading peaks with a maximum that exceeds J

Q
should be assessed using a special analysis beyond the scope of the FASTRAN retardation model.

Originality/value

– Measurements of fatigue crack growth on specimens made from 7475 T7351 aluminium alloy were carried out. The results indicated that simultaneously evaluating fatigue crack increments after application of the load amplitude above J

Q
and subcritical increments caused by the loads at high stress intensity factors is difficult. Experiments demonstrated that if the fatigue crack reaches a specific length, the maximal amplitude load induces considerable crack growth retardation.
Does the presence of placental basal plate myometrial fibres increase the risk of subsequent morbidly adherent placenta: a case–control study
Authors: Miller ES , Linn RL , Ernst LM
Published: August 2015

Objective

Antenatal diagnosis of morbidly adherent placenta has been shown to improve outcomes, but existing predictors lack sensitivity. Our objective was to determine whether the presence of myometrial fibres attached to the placental basal plate (BPMYO) in an antecedent pregnancy is associated with subsequent morbidly adherent placenta.

Design

A case–control study.

Setting

Departments of Obstetrics and Gynecology and Pathology, Northwestern University, Chicago, IL, USA.

Sample

Women who had at least two pregnancies with placental pathological evaluation.

Methods

Cases were defined as women with evidence of morbidly adherent placenta (both clinically and pathologically) in their most recent pregnancy whereas women without evidence of morbidly adherent placenta served as controls. Pathological specimens of placentas from previous pregnancies were evaluated for BPMYO. The presence of BPMYO on a previous placenta was evaluated to determine whether it could be used to improve the antenatal diagnosis of morbidly adherent placenta.

Results

Of the 25 cases of morbidly adherent placenta, 19 (76%) had BPMYO present on their previous placenta compared with 41 (41%) of controls (odds ratio 4.8, 95% CI 1.8–13.0). Adding BPMYO to a regression including other risk factors for morbidly adherent placenta (i.e. maternal age, number of previous caesarean sections, placenta praevia, previous multiple gestation, any previous curettage, and ultrasonographic suspicion of placenta accreta) significantly improved the sensitivity of antenatal diagnosis of morbidly adherent placenta (61% versus 39%, P < 0.001) without a change in specificity (97% versus 97%, P = 1.00).

Conclusion

BPMYO on previous placental pathology is associated with an increased risk of morbidly adherent placenta in a subsequent pregnancy. These findings may shed light on the pathophysiology of accreta and inform future research on predictors of accreta.

Tweetable abstract

Previous basal plate myometrium improves the ability to detect subsequent morbidly adherent placenta.
Biomarkers associated with severe hypoglycaemia and death in ACCORD
Authors: Chow L. S. , Chen H. , Miller M. E. , Marcovina S. M. , Seaquist E. R.
Published: August 2015

Aims and hypothesis

In patients with Type 2 diabetes, intensive glycaemic control is associated with hypoglycaemia and possibly increased mortality. However, no blood biomarkers exist to predict these outcomes. Using participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, we hypothesized that insulin deficiency and islet autoantibodies in patients with clinically diagnosed Type 2 diabetes would be associated with severe hypoglycaemia and death.

Methods

A nested case–control study design was used. A case (n = 86) was a participant who died with at least one episode of severe hypoglycaemia, defined as hypoglycaemia requiring assistance, at any point during ACCORD follow‐up. A control (n = 344) was a participant who did not die and did not have severe hypoglycaemia during follow‐up. Each case was matched to four controls (glycaemic intervention arm, race, age and BMI). Baseline insulin deficiency (fasting C–peptide ≤ 0.15 nmol/l) and islet autoantibodies [glutamic acid decarboxylase (GAD), tyrosine phosphatase‐related islet antigen 2 (IA2), insulin (IAA) and zinc transporter (ZnT8)] were measured. Conditional logistic regression with and without adjustment for age, BMI and diabetes duration was used.

Results

Death during ACCORD in those who experienced at least one episode of severe hypoglycaemia was associated with insulin deficiency [OR 4.8 (2.1, 11.1): P < 0.0001], GAD antibodies [OR 2.3 (1.1, 5.1): P = 0.04], the presence of IAA or baseline insulin use [OR 6.1 (3.5,10.7): P < 0.0001], which remained significant after adjusting for age, BMI, and diabetes duration. There was no significant association with IA2 or ZnT8 antibodies.

Conclusions

In patients with Type 2 diabetes, C–peptide or GAD antibodies may serve as blood biomarkers predicting higher odds of subsequent severe hypoglycaemia and death. (Clinical Trial Registry No: NCT00000620, www.clinicaltrials.gov for original ACCORD study)