bluuebunny/crossref_metadata_2025 huggingface dataset:
Preliminary X-ray diffraction analysis of CfaA, a molecular chaperone essential for the assembly of CFA/I fimbriae of human enterotoxigenic Escherichia coli
Authors: Bao Rui , Esser Lothar , Poole Steven , McVeigh Annette , Chen Yu-xing , Savarino Stephen J. , Xia Di
Published: January 2014

Understanding of pilus bioassembly in Gram-negative bacteria stems mainly from studies of P pili and type 1 fimbriae of uropathogenic Escherichia coli, which are mediated by the classic chaperone–usher pathway (CUP). However, CFA/I fimbriae, a class 5 fimbria and intestinal colonization factor for enterotoxigenic E. coli (ETEC), are proposed to assemble via the alternate chaperone pathway (ACP). Both CUP and ACP fimbrial bioassembly pathways require the function of a periplasmic chaperone, but their corresponding proteins share very low similarity in primary sequence. Here, the crystallization of the CFA/I periplasmic chaperone CfaA by the hanging-drop vapor-diffusion method is reported. X-ray diffraction data sets were collected from a native CfaA crystal to 2 Å resolution and to 1.8 and 2.8 Å resolution, respectively, from a lead and a platinum derivative. These crystals displayed the symmetry of space group C2, with unit-cell parameters a = 103.6, b = 28.68, c = 90.60 Å, β = 119.7°. Initial phases were derived from multiple isomorphous replacement with anomalous scattering experiments using the data from the platinum and lead derivatives. This resulted in an interpretable electron-density map showing one CfaA molecule in an asymmetric unit. Sequence assignments were aided by anomalous signals from the heavy-atom derivatives. Refinement of the atomic model of CfaA is ongoing, which is expected to further understanding of the essential aspects and allowable variations in tertiary structure of the greater family of chaperones involved in chaperone–usher mediated bioassembly.
Structure determination of BA0150, a putative polysaccharide deacetylase from Bacillus anthracis
Authors: Strunk Robert J. , Piemonte Katrina M. , Petersen Natasha M. , Koutsioulis Dimitris , Bouriotis Vassilis , Perry Kay , Cole Kathryn E.
Published: January 2014

Polysaccharide deacetylases are bacterial enzymes that catalyze the deacetylation of acetylated sugars on the membranes of Gram-positive bacteria, allowing them to be unrecognized by host immune systems. Inhibition of these enzymes would disrupt such pathogenic defensive mechanisms and therefore offers a promising route for the development of novel antibiotic therapeutics. Here, the first X-ray crystal structure of BA0150, a putative polysaccharide deacetylase from Bacillus anthracis, is reported to 2.0 Å resolution. The overall structure maintains the conserved (α/β)8 fold that is characteristic of this family of enzymes. The lack of a catalytic metal ion and a distinctive metal-binding site, however, suggest that this enzyme is not a functional polysaccharide deacetylase.
Crystallization and preliminary X-ray diffraction analysis of human DNA primase
Authors: Baranovskiy Andrey G. , Gu Jianyou , Babayeva Nigar D. , Agarkar Vinod B. , Suwa Yoshiaki , Tahirov Tahir H.
Published: January 2014

Human primase synthesizes RNA primers and transfers them to the active site of Pol α with subsequent extension with dNTPs. Human primase is a heterodimer of two subunits: a small catalytic subunit (p49) and a large subunit (p58). The structural details of the initiation and elongation steps of primer synthesis, as well as primer length counting, are not known. To address these questions, structural studies of human primase were initiated. Two types of crystals were obtained. The best diffracting crystals belonged to space group P1, with unit-cell parameters a = 86.2, b = 88.9, c = 94.68 Å, α = 93.82, β = 96.57, γ = 111.72°, and contained two heterodimers of full-length p49 and p59 subunits in the asymmetric unit.
Purification, crystallization and preliminary X-ray diffraction analysis of the N-acetyltransferase SAV0826 from Staphylococcus aureus
Authors: Srivastava Parul , Khandokar Yogesh B. , Forwood Jade K.
Published: January 2014

Staphylococcus aureus is a prevalent microorganism that is capable of causing a wide range of infections and diseases. Several strains of this bacterial species have developed antibiotic resistance to methicillin and vancomycin, and higher death rates are still being reported each year owing to multidrug-resistant strains. Certain GCN5-related N-acetyltransferases (GNATs) exhibit a broad substrate range, including aminoglycosides, histones, other proteins and serotonin, and have been implicated in antibiotic drug resistance. Here, the expression, purification, crystallization and preliminary X-ray diffraction analysis of a GNAT from S. aureus (SaNAT) are reported. SaNAT was recombinantly expressed and crystallized by the hanging-drop vapour-diffusion method at 296 K, and the crystals diffracted to 1.7 Å resolution on the MX2 beamline at the Australian Synchrotron. The crystals belonged to space group P43212, with unit-cell parameters a = b = 84.86, c = 49.06 Å, α = β = γ = 90°. A single molecule is likely to be present in the asymmetric unit. A full structural and functional analysis is currently being undertaken to provide novel insights into the protein function, which in turn may provide a basis for drug design.
The structure of human tau-tubulin kinase 1 both in the apo form and in complex with an inhibitor
Authors: Kiefer Susan E. , Chang ChiehYing J. , Kimura S. Roy , Gao Mian , Xie Dianlin , Zhang Yaqun , Zhang Guifen , Gill Martin B. , Mastalerz Harold , Thompson Lorin A. , Cacace Angela M. , Sheriff Steven
Published: January 2014

Tau-tubulin kinase 1 (TTBK1) is a dual-specificity (serine/threonine and tyrosine) kinase belonging to the casein kinase 1 superfamily. TTBK1 is a neuron-specific kinase that regulates tau phosphorylation. Hyperphosphorylation of tau is implicated in the pathogenesis of Alzheimer's disease. Two kinase-domain constructs of TTBK1 were expressed in a baculovirus-infected insect-cell system and purified. The purified TTBK1 kinase-domain proteins were crystallized using the hanging-drop vapor-diffusion method. X-ray diffraction data were collected and the structure of TTBK1 was determined by molecular replacement both as an apo structure and in complex with a kinase inhibitor.
Modern antifouling compositions Part III. The effect of filler and extender pigments on the efficiency of organotin polymers, copper antifouling paints
Authors: Mounir  , El‐Malek M.Abd , Nagi  , Messiha N. , Magdy  , Ayoub M.H.
Published: January 2014

The effect of pigment filler and extender on the antifouling efficiency of six compositions containing organotin polymer is studied. The binder mixture is a blend containing a copolymer of tri‐n‐butyltin methacrylate and methylmeth acrylate (OTP) with 22% tin content, a vinyl copolymer with its external plasticizer and little amount of rosin. Cuprous oxide was added as a supplementary toxin with the OTP. Leaching rates of microamounts of copper and tin were determined for a period of nearly one year applying standard techniques. Painted plates were immersed in Suez Canal waters at Port‐Said for more than 36 months. Comparison between different fillers and extenders on the antifouling behaviour of painted surfaces is shown. Compositions containing cellite and china clay exhibited the maximum antifouling performance.
Strategic facilities planning
Authors: Kovac E.J. , Thompson R.A.
Published: January 2014

Bellcore, a large telecommunications engineering consortium, used several methodological innovations to develop a long‐range strategic facilities plan that has also proved to be highly adaptable—a key advantage in a rapidly changing business environment.
Image‐ray Tomography
Authors: Dell Sergius , Gajewski Dirk , Tygel Martin
Published: January 2014

Seismic tomography is a well‐established approach to invert smooth macro‐velocity models from kinematic parameters, such as traveltimes and their derivatives, which can be directly estimated from data. Tomographic methods differ more with respect to data domains than in the specifications of inverse‐problem solving schemes. Typical examples are stereotomography, which is applied to prestack data and Normal‐Incidence‐Point‐wave tomography, which is applied to common midpoint stacked data. One of the main challenges within the tomographic approach is the reliable estimation of the kinematic attributes from the data that are used in the inversion process. Estimations in the prestack domain (weak and noisy signals), as well as in the post‐stack domain (occurrence of triplications and diffractions leading to numerous conflicting dip situations) may lead to parameter inaccuracies that will adversely impact the resulting velocity models. To overcome the above limitations, a new tomographic procedure applied in the time‐migrated domain is proposed. We call this method Image‐Incident‐Point‐wave tomography. The new scheme can be seen as an alternative to Normal‐Incidence‐Point‐wave tomography. The latter method is based on traveltime attributes associated with normal rays, whereas the Image‐Incidence‐Point‐wave technique is based on the corresponding quantities for the image rays. Compared to Normal‐Incidence‐Point‐wave tomography the proposed method eases the selection of the tomography attributes, which is shown by synthetic and field data examples. Moreover, the method provides a direct way to convert time‐migration velocities into depth‐migration velocities without the need of any Dix‐style inversion.
Fault imaging in sparsely sampled 3D seismic data using common‐reflection‐surface processing and attribute analysis – a study in the Upper Rhine Graben
Authors: Buness Hermann A. , von Hartmann Hartwig , Rumpel Hanna‐Maria , Krawczyk Charlotte M. , Schulz Rüdiger
Published: January 2014

Cost reduction in seismic reconnaissance is an issue in geothermal exploration and can principally be achieved by sparse acquisition. To address the adherent decrease in signal/noise ratio, the common‐reflection‐surface method has been proposed. We reduced the data density of an existing 3D dataset and evaluated the results of common‐reflection‐surface processing using seismic attributes. The application of the common‐reflection‐surface method leads in all cases to an improvement of the signal/noise ratio. The most distinct improvement can be seen in the low fold regions. The improvement depends strongly on the midpoint aperture, and there is a tradeoff between reflector continuity and horizontal resolution. If small scale targets are to be imaged, a small aperture size is necessary, which may be far below the Fresnel zone for a specific reflector. The substantial reduction of the data density leads in our case to an irrecoverable information loss.
Anatomy of a population cycle: the role of density dependence and demographic variability on numerical instability and periodicity
Authors: Row Jeffrey R. , Wilson Paul J. , Murray Dennis L.
Published: January 2014

Determining the causes of cyclic fluctuations in population size is a central tenet in population ecology and provides insights into population regulatory mechanisms. We have a firm understanding of how direct and delayed density dependence affects population stability and cyclic dynamics, but there remains considerable uncertainty in the specific processes contributing to demographic variability and consequent change in cyclic propensity.

Spatiotemporal variability in cyclic propensity, including recent attenuation or loss of cyclicity among several temperate populations and the implications of habitat fragmentation and climate change on this pattern, highlights the heightened need to understand processes underlying cyclic variation. Because these stressors can differentially impact survival and productivity and thereby impose variable time delays in density dependence, there is a specific need to elucidate how demographic vital rates interact with the type and action of density dependence to contribute to population stability and cyclic variation.

Here, we address this knowledge gap by comparing the stability of time series derived from general and species‐specific (Canada lynx: Lynx canadensis; small rodents: Microtus, Lemmus and Clethrionomys spp.) matrix population models, which vary in their demographic rates and the direct action of density dependence.

Our results reveal that density dependence acting exclusively on survival as opposed to productivity is destabilizing, suggesting that a shift in the action of population regulation toward reproductive output may decrease cyclic propensity and cycle amplitude. This result was the same whether delayed density dependence was pulsatile and acted on a single time period (e.g. t−1, t−2 or t−3) vs. more constant by affecting a successive range of years (e.g. t−1,…, t−3).

Consistent with our general models, reductions in reproductive potential in both the lynx and small rodent systems led to notably large drops in cyclic propensity and amplitude, suggesting that changes in this vital rate may contribute to the spatial or temporal variability observed in the cyclic dynamics of both systems.

Collectively, our results reveal that the type of density dependence and its effect on different demographic parameters can profoundly influence numeric stability and cyclic propensity and therefore may shift populations across the cyclic‐to‐noncyclic boundary.
An International Comparison of the Incidence of Public Sector Whistle‐Blowing and the Prediction of Retaliation: Australia, Norway, and the US
Authors: Miceli Marcia P. , Near Janet P.
Published: January 2014

We compare results of several large‐scale survey studies of whistle‐blowing by public sector employees, from samples in Australia, Norway, and the United States. Specifically, we review incidence rates of wrongdoing, whistle‐blowing and retaliation, as perceived by thousands of respondents employed by many government agencies in these countries. Despite differences in measurement in the studies and variation in results, findings suggest that wrongdoing was quite frequently observed and was reported in many cases. Retaliation resulted for far fewer than half of the whistle‐blowers, in all three nations. We also compare findings from the various studies concerning variables that predicted retaliation against whistle‐blowers in the different samples. Differences in results across the three countries add to existing evidence that country and workplace cultures can affect the whistle‐blowing process.
Women Police in Post‐Fitzgerald Queensland: A 20 Year Review
Authors: Prenzler Tim , Drew Jacqueline
Published: January 2014

The Fitzgerald report was the catalyst for major reforms to Queensland's system of government and criminal justice, and included explicit recommendations related to women in policing. Reforms led to the removal of discriminatory barriers and significant improvements in the recruitment and promotion of women. However, these changes provoked a backlash in the 1990s that led to reductions in female recruitment. A return to less discriminatory policies eventually ensued, with steady improvements on key equity indicators. This paper provides a historical perspective on developments over the two decades since Fitzgerald, and includes a critical analysis of the implementation of contemporary equity and diversity strategies within the policing context. Recruitment of women police in Queensland has plateaued at one‐third and progress in the overall number of sworn women and women in management is slow. The paper concludes by emphasising the wider lessons for a more developed and proactive gender equity program in public sector employment and policing.
What's Queer about Political Science?
Authors: Smith Nicola J. , Lee Donna
Published: January 2014

Research Highlights and Abstract

The study of gender, sexuality—and, in particular, queer theory—is central to the social sciences and humanities. Our analysis of citation practices shows that queer theorist Judith Butler is one of the most cited social theorists of all time. Yet political science remains distinctly untroubled by queer theory, and gender and sexuality are frequently treated as marginal (not central) concerns. We argue that queer theory has much to offer political science, not only by highlighting the importance of sexuality and the body but also in analysing ‘power’ and in politicising ‘the political’ itself. We suggest that the ‘queering’ of political science is long overdue, not least through politicising processes of knowledge-production in the discipline.

There is something queer (by which we mean strange) going on in the scholarly practice of political science. Why are political science scholars continuing to disregard issues of gender and sexuality—and in particular queer theory—in their lecture theatres, seminar rooms, textbooks, and journal articles? Such everyday issues around common human experience are considered by other social scientists to be central to the practice and theory of social relations. In this article we discuss how these commonplace issues are being written out of (or, more accurately, have never been written in to) contemporary political science. First, we present and discuss our findings on citation practice in order to evidence the queerness of what does and does not get cited in political science scholarship. We then go on to critique this practice before suggesting a broader agenda for the analysis of the political based on a queer theoretical approach.
Making Practicality a Virtue: Morality, Law, and Fortitude in Giovanni da Legnano's De Bello
Authors: Grabher Jasonne M.
Published: January 2014

While Giovanni da Legnano's De bello (ca.1360) deals primarily with practical issues related to the law of war, he also delved into the areas of moral philosophy and theology by examining the cardinal virtue fortitude. Giovanni's interest in fortitude continues longstanding medieval concerns about the morality of war and other forms of sanctioned violence, but his approach to the subject is that of a jurist attempting to bring licit violence more firmly under the rule of law. The historical context in which he wrote, furthermore, provides a useful framework for understanding his motivations and his treatment of various issues in the work.
Theology, Practice, and Policy at the Turn of the Thirteenth Century: the Papacy and Peter Lombard
Authors: Monagle Clare
Published: January 2014

Famously, the Fourth Lateran Council took place in 1215 and offered a bold new wave of papal legislation. Importantly, the Council confessed cum petro, with Peter Lombard. This was an unprecedented endorsement of a scholastic theologian. By confessing cum petro, the papacy placed Peter Lombard's Sentences at the heart of its bold reforming agenda. There has been very little historical analysis of the meanings of this endorsement. This article will attempt to situate the logic of this endorsement within the larger context of the Council, as well as the increasing formalisation of the Schools of Paris, which culminated in the founding of the University of Paris in that same year.
Law, Theology, and Morality: Conceptions of the Rights to Relief of the Poor in the Twelfth and Thirteenth Centuries
Authors: Taliadoros Jason
Published: January 2014

This article presents an analysis of certain ways of thinking about law and its relationship to the poor, in particular the rights and entitlements of the poor to the basic necessities of life and the obligations of society to provide those necessities. It focuses on the works of Peter the Chanter and his “circle” at Paris in the late twelfth and early thirteenth centuries. Significant in their writings on the quandary between respect for private property and the need to allow those in need to take a share of this private property in order to survive is their negotiation of the intellectual boundaries and understandings between law, theology, and morality. In addition, an understanding of their discussions in light of canonistic and theological works of the time reveal a hitherto under‐appreciated contribution to the “subjective rights” language in Peter the Chanter.
Attendant to a Higher Judge: Competing Paradigms of Legal Practice in the Thought of Alexander Neckam (1157–1217)
Authors: Zahora Tomas
Published: January 2014

The end of the twelfth century was a period of nascent professionalisation of legal practitioners. But this transformation was not immediate, and older paradigms of practicing justice coexisted with new. In this article I look at the discourse of justice from the perspective of a practitioner who did not pursue a legal career, in order to examine how the new developments were perceived by contemporaries. The English Augustinian Canon Alexander Neckam (1157–1217) studied canon law along with the arts and theology in Paris, and served as a papal judge delegate. Yet his interests were mainly those of a theologian and educator, and his treatment of law and justice has been evaluated by historians as lacking proper legal understanding. As I argue, Neckam does have a well‐developed conception of law and justice. It is anchored in the notion of justice as embodied in the person exercising it, and in a programme of moral education associated with the exegetical method of tropology. Neckam's notion of justice is an expression of a well‐oiled educational paradigm as much as a statement of prestige, both of which were challenged by students willing to bypass traditional educational methods and progress more directly to the study of law. His response reveals the difficult situation in which many arts‐trained practitioners found themselves. While they had the rhetorical skills to argue that specialised legal training could result in morally flawed judges and unjust decisions, they were often relegated to watching the honours and wealth to which they grew accustomed gradually shift to the very men whose focused expertise they disparaged.
“Being Scorned by One's Own is Perfect Joy”: The Strange Case of Dorothy Day
Authors: Phillips Jacob
Published: January 2014

Dorothy Day has long been seen as an enigma in understandings of twentieth‐century American Catholicism. With the publication of Dorothy Day's extensive letters and diaries in 2008, the enigmatic character of Day's relation to various fault lines of Catholic identity has been made even more apparent. Day's ability to sidestep received opinion, in order to disclose (arguably) something of an inner resonance between apparently differing viewpoints, often left her sitting uneasily with the proponents of different positions across the spectrum of Catholic thinking, causing her to quote St Francis, saying that “being scorned by one's own is perfect joy.” This review article gives a summary of the contributions made by these volumes to understandings of Day's life and work, before discussing three particular fault lines, where Day's ability to straddle differing positions is most perceptible: her practice of pre‐Conciliar spirituality, her attitude to ecclesiastical authority, and her position on matters pertaining to gender and sexuality.
Evaluation of cheese meltability using convection and conduction melt profilers
Authors: Ko Sanghoon , Gunasekaran Sundaram
Published: January 2014

The University of Wisconsin (UW) Melt Profiler was operated under convection and conduction heating modes for evaluating the melt/flow properties of cheese. Five processed cheeses, each with a different solid fat index (SFI = 1+, 5−, 5+, 6− and 8+), were tested. In general, the higher the SFI of the cheese, the lower the time and temperature at the softening point. Similar trends were also observed between the cheese SFI values and the time and temperature at the rapid flow point. As conduction heating is more effective than convection heating, the heating method affected the cheese melt/flow parameters remarkably. Furthermore, TSP and TRF tended to be higher when the cheeses were tested at higher temperatures.
Transcriptomic response of cowpea bruchids to N‐acetylglucosamine‐specific lectins
Authors: Wang Li‐Hua , Chi Yong Hun , Guo Feng‐Guang , Li‐Byarlay Hongmei , Balfe Susan , Fang Ji‐Chao , Pittendrigh Barry R. , Zhu‐Salzman Keyan
Published: January 2014

Griffonia simplicifolia lectin II (GSII) and wheat germ agglutinin (WGA) are N‐acetylglucosamine‐binding lectins. Previous studies demonstrated that they have anti‐insect activity, a property potentially useful in pest control. To gain some insight into the insect response to dietary lectins, we performed transcriptomic analysis using the cowpea bruchid (Callosobruchus maculatus) midgut microarray platform we built. Compared to the nonnutritional cellulose treatment, dietary lectins induced more profound changes in gene expression. Ingestion of relatively high doses of lectins for 24 h resulted in alteration of gene expression involved in sugar and lipid metabolism, transport, development, defense, and stress tolerance. Metabolic genes were largely downregulated. Moreover, we observed disorganized microvilli resulting from ingestion of WGA. This morphological change is consistent with the lectin‐induced changes in genes related to midgut epithelial cell repair. In addition, suboptimal nutrient conditions may serve as a stress signal to trigger senescence processes, leading to growth arrest and developmental delay.
Anti‐obesity effect of Allomyrina dichotoma (Arthropoda: Insecta) larvae ethanol extract on 3T3‐L1 adipocyte differentiation
Authors: Chung Mi Yeon , Yoon Young‐Il , Hwang Jae‐Sam , Goo Tae‐Won , Yun Eun‐Young
Published: January 2014

Although Korean horn beetle (Allomyrina dichotoma) larvae have been long used as an oriental medicine for the treatment of liver diseases in Korea, there is little scientific evidence of their effects. In this study, we investigated the anti‐obesity activity of A. dichotoma larvae extract (ADE) by using 3T3‐L1 cells as an in vitro model of adipogenesis. To analyze its role as an inhibitor of adipogenesis, 3T3‐L1 cells were treated with both ADE and differentiation inducer (DM) at the same time, and then the amount of lipid was quantified. We then analyzed the mRNA and protein expression level of adipogenic or lipogenic genes. The results showed that formation of lipid droplets in differentiated 3T3‐L1 cells was markedly decreased, and triglyceride content was reduced by 22.15% in response to 2000 μg/mL ADE. In addition, ADE downregulated mRNA and protein expression of transcription factors peroxisome proliferator‐activated receptor (PPAR)‐γ and CCAAT/enhancer binding protein (C/EBP)‐α implicated in adipogenesis, and significantly decreased the expression levels of adipocyte fatty acid binding protein (aP2), fatty acid synthase (FAS), stearoyl‐coenzyme desaturase‐1 (SCD1), and lipoprotein lipase (LPL) related to lipogenesis. Our results demonstrate that ADE suppressed adipogenesis and lipogenesis in 3T3‐L1 cells, suggesting that ADE has anti‐obesity activity as a food supplement.
Microstructural analysis on the testicular cyst of the wolf spider by 3D volume rendering
Authors: Kim Hoon , Kim Jae‐Kyung , Moon Myung‐Jin
Published: January 2014

Spermatogenesis has long been a major research area in understanding the development of living organisms. In vertebrates, sperm is produced along the wall of the seminiferous tubules, leaving spermatogonia in the outermost layer, which undergo cell division and differentiation. However, sperm in many invertebrates is developed in a testicular cyst, which contains germ cells at the same developmental stages. On the contrary, in spiders, it is very difficult to count the exact number of cells in a cyst, since each spermatid gets transformed to a round sperm ball within the cyst through the flagellar coiling process. Therefore, in this study, we applied a 3D rendering technique to analyze the exact number of germ cells per cyst in spiders. For image processing and reconstruction, serial section images were scanned and reconstructed into 3D images. Upon successful 3‐dimensional reconstruction of testicular cysts, the exact number of germ cells produced from a single cyst appeared to be 64, 26 which indicates that a spider spermatogonium undergoes 6 cell divisions to produce spermatozoa.
β‐elemene reverses the drug resistance of A549/DDP lung cancer cells by activating intracellular redox system, decreasing mitochondrial membrane potential and P‐glycoprotein expression, and inducing apoptosis
Authors: Yao Chengcai , Jiang Jie , Tu Yuanrong , Ye Shefang , Du Haoxin , Zhang Yi
Published: January 2014

Background

β‐elemene (β‐ELE) injection is a new anticancer drug extracted from Curcuma zedoaria Roscoe that has been widely used to treat malignant tumors. Recent studies show that β‐ELE reverses the drug resistance of tumor cells. To explore the possible mechanisms of β‐ELE, we investigated its effects on cisplatin (DDP)‐resistant human lung adenocarcinoma A549/DDP cells.

Methods

The effects of β‐ELE on the growth of A549/DDP cells in vitro were determined by MTT assay. Apoptosis was assessed by fluorescence microscopy with Hoechst 33258 staining, flow cytometry with Annexin V‐FITC/propium iodide double staining; mitochondrial membrane potential using JC‐1 fluorescence probe and laser confocal scanning microscopy, and intracellular reactive oxygen species levels were measured by 2’,7'‐dichlorfluorescein‐diacetate staining and flow cytometry; and contents of cytosolic glutathione were determined by glutathione assay kits. Intracellular Rhodamine‐123 fluorescence intensity was detected by flow cytometry, and the expression of P‐glycoprotein (P‐gp) was detected by Western blotting.

Results

β‐ELE inhibited the proliferation of A549/DDP cells in a time‐ and dose‐dependent manner. Furthermore, β‐ELE enhanced the sensitivity of A549/DDP cells to cisplatin and reversed the drug resistance of A549/DDP cells. Consistent with a role in activating apoptosis, β‐ELE decreased mitochondrial membrane potential, increased intracellular reactive oxygen species concentration and intracellular accumulation of Rhodamine‐123, decreased the cytoplasmic glutathione levels and the expression of P‐gp in a time‐ and dose‐dependent manner.

Conclusions

These results define a pathway of β‐ELE function that involves decreased mitochondrial membrane potential and P‐gp expression activated intracellular redox system, and induced apoptosis leading to reverse drug resistance.
Pre‐treatment of bupivacaine‐induced cardiovascular depression using different lipid formulations of propofol
Authors: YILMAZ M. , CELEBI H. , AKCALI D. , GUREL N.
Published: January 2014

Background

Pre‐treatment with lipid emulsions has been shown to increase lethal doses of bupivacaine, and the lipid content of propofol may alleviate bupivacaine‐induced cardiotoxicity. The aim of this study is to investigate the effects of propofol in intralipid or medialipid emulsions on bupivacaine‐induced cardiotoxicity.

Methods

Rats were anaesthetised with ketamine and were given 0.5 mg/kg/min propofol in intralipid (Group P), propofol in medialipid (Group L), or saline (Group C) over 20 min. Thereafter, 2 mg/kg/min bupivacaine 0.5% was infused. We recorded time to first dysrhythmia occurrence, respective times to 25% and 50% reduction of the heart rate (HR) and mean arterial pressure, and time to asystole and total amount of bupivacaine consumption. Blood and tissue samples were collected following asystole.

Results

The time to first dysrhythmia occurrence, time to 25% and 50% reductions in HR, and time to asystole were longer in Group P than the other groups. The cumulative bupivacaine dose given at those time points was higher in Group P. Plasma bupivacaine levels were significantly lower in Group P than in Group C. Bupivacaine levels in the brain and heart were significantly lower in Group P and Group L than in Group C.

Conclusion

We conclude that pre‐treatment with propofol in intralipid, compared with propofol in medialipid or saline, delayed the onset of bupivacaine‐induced cardiotoxic effects as well as reduced plasma bupivacaine levels. Further studies are needed to explore tissue bupivacaine levels of propofol in medialipid and adapt these results to clinical practice.
Gallbladder carcinoma: a New Zealand centre's 10‐year experience with presentation, ethnic diversity and survival rate
Authors: Lilic Nikola , Addison Ben , Hammodat Hisham
Published: January 2014

Background

Gallbladder cancer is a high‐mortality cancer with a wide range of incidence worldwide. Some indigenous populations are known to have a higher incidence of gallbladder cancer. Commonly, it is incidentally discovered during routine gallbladder surgery. The primary aim was to determine the incidence and characteristics of gallbladder cancer in a New Zealand population. The secondary aim was to determine if inequalities in gallbladder cancer rates between Māori and non‐Māori have decreased.

Methods

A retrospective cohort study utilizing an online database was conducted to identify all patients with gallbladder malignancy treated in the Waitemata District Health Board from 2003 to 2013. The outcomes measured were staging of cancer, histology, ethnicity, incidental finding and survival rates.

Results

The age‐standardized incidence (ASI) rate of gallbladder carcinoma is 0.60/100 000. The gender‐specific ASI rates were 0.21/100 000 (men) and 0.76/100 000 (women). The incidence for Māori was 0.96/100 000 (men) and 1.37/100 000 (women). Gallbladder carcinoma was found incidentally in 0.44% of cholecystectomies, which made up 46.2% of all cases. Right upper quadrant pain was the most common presenting symptom (74.4%). Surgery was the most common treatment modality (66.7%). Mean survival across all patients was 12.24 months.

Conclusion

Our study found that the ASI of gallbladder carcinoma when compared with the Koea et al. study has decreased for men from New Zealand, but appears to have increased slightly for women from New Zealand. The raw incidence for Māori men and women appears to have decreased, but inequality in gallbladder cancer incidence between Māori and non‐Māori remains.
Diversity in Classrooms: The Relationship between Deliberative and Associative Opportunities in School and Later Electoral Engagement
Authors: Kawashima‐Ginsberg Kei , Levine Peter
Published: January 2014

Previous research has found that attending racially pluralistic high schools is associated with a reduced likelihood of future electoral and civic engagement. Analysis of a national survey of 18–24 year olds after the 2012 election confirms this finding. However, certain school and family practices and extracurricular activities appear to compensate. Discussion of controversial current issues in social studies classes diminishes the negative association between attending a racially pluralistic school and electoral engagement. School‐based discussion is particularly important for young people who attend pluralistic schools and who do not participate in political discussion at home. Opportunities to associate with peers who share common interests through issue‐oriented groups predict electoral engagement. Considering that strong arguments can be made in favor of racial diversity in schools, it is important to compensate for the lessened electoral engagement in diverse schools by creating policies and teacher preparation resources that promote high‐quality discussion of controversial issues in classrooms, and by encouraging students to participate in extracurricular groups that address political issues.
Diminished Control and Unmet Expectations: Testing a Model of Adjustment to Unplanned Cesarean Delivery
Authors: DeLuca Robyn Stein , Lobel Marci
Published: January 2014

Compared to vaginal deliveries, surgical (cesarean) deliveries are associated with more complications, longer recovery, lower satisfaction, and greater risk of postpartum mood disturbances. Despite a steep rise in rates of surgical delivery, there have been few theoretically founded investigations of the mechanisms by which delivery method has an effect on psychosocial outcome. We tested a model of adjustment to unplanned cesarean delivery, focusing on two mediators: diminished control over labor and delivery; and unmet expectations of control over childbirth. Participants were 164 women anticipating a normal vaginal childbirth. Women who delivered by unplanned surgical delivery (24% of the sample) experienced significantly lower childbirth satisfaction than women delivering vaginally. As hypothesized, the association of delivery method with childbirth satisfaction was mediated by diminished control and unmet expectations, even after controlling for other predictors. Differences were not found between delivery groups in postpartum depressed mood. Irrespective of delivery method, perceived control during labor and delivery was strongly associated with childbirth satisfaction and lower depressed mood. Findings suggest that enabling women to exert desired control over childbirth is likely to enhance satisfaction and reduce the likelihood of postpartum mood disturbance. Implications for policies relevant to hospitals, employers, insurance companies, and legal practice are discussed.
The impact of native large herbivores and fire on the vegetation dynamics in the Cape renosterveld shrublands of South Africa: insights from a six‐yr field experiment
Authors: Radloff Frans G.T. , Mucina Ladislav , Snyman Dirk
Published: January 2014

Question

Renosterveld – a vegetation complex within the Fynbos Biome of South Africa – occurs in multiple structural states, including shrublands and various types of grasslands, lawns and herb‐lands. Uncertainty exists over whether the present unpalatable shrubland state might have replaced a historical grassland state. Settled agriculture characterized by fixed burning cycles and overgrazing by livestock has been blamed for this putative change. However, the disappearance of native large herbivores has also been implicated. Understanding the drivers responsible for putative state changes is of importance for conservation of this critically endangered vegetation type.

Location

Renosterveld shrublands and grasslands of the De Hoop Nature Reserve, Western Cape Province, South Africa.

Methods

Three structural states of renosterveld (grazing lawn, tussock grassland and shrubland) were subjected to an experiment involving fire (burned/unburned) and herbivory (grazed/ungrazed by native mesoherbivores). Using animal exclosures and experimental burning, we measured the responses of the biomass of major plant functional types over 6 yrs to test whether switches between states occur in order to discern the drivers of these changes. The data were analysed using permutational manova, Fisher's exact contingency tests and NMDS.

Results

Herbivory (but not fire) had significant effects on lawn and tussock grassland biomass. Palatable shrubs proliferated in tussock grassland protected from herbivory. Unpalatable shrubs invaded burned lawn habitats exposed to herbivory. The vegetation composition of the shrubland state was affected by fire, herbivory and by the interaction between the two. Burned and grazed shrubland reverted to a dense canopy unpalatable state, while shrubland plots protected from grazing became palatable shrubland with a grass understorey. Palatable shrub species increased in the unburned and ungrazed shrubland plots, while the biomass of unpalatable shrubs declined in both the unburned grazed and exclosure plots.

Conclusion

We found no evidence supporting the hypothesis that the disappearance of native large herbivores led to the conversion of tussock grassland into unpalatable shrubland. Instead, the removal of native browsers caused palatable shrubs to dominate tussock grassland areas. Unpalatable shrubland is retained through a combination of fire and herbivory, but how this state established and persisted historically remains undetermined. Temporary relief from large herbivore grazing after unpalatable shrubland has been burned is recommended if a more open grassland state is the desired target.
Mapping the Human Toxome by Systems Toxicology
Authors: Bouhifd Mounir , Hogberg Helena T. , Kleensang Andre , Maertens Alexandra , Zhao Liang , Hartung Thomas
Published: January 2014

Toxicity testing typically involves studying adverse health outcomes in animals subjected to high doses of toxicants with subsequent extrapolation to expected human responses at lower doses. The low‐throughput of current toxicity testing approaches (which are largely the same for industrial chemicals, pesticides and drugs) has led to a backlog of more than 80,000 chemicals to which human beings are potentially exposed whose potential toxicity remains largely unknown. Employing new testing strategies that employ the use of predictive, high‐throughput cell‐based assays (of human origin) to evaluate perturbations in key pathways, referred as pathways of toxicity, and to conduct targeted testing against those pathways, we can begin to greatly accelerate our ability to test the vast ‘storehouses’ of chemical compounds using a rational, risk‐based approach to chemical prioritization and provide test results that are more predictive of human toxicity than current methods. The NIH Transformative Research Grant project Mapping the Human Toxome by Systems Toxicology aims at developing the tools for pathway mapping, annotation and validation as well as the respective knowledge base to share this information.
Distribution and type of sticky spots at the centre of a deglacial streamlined lobe in northeastern Manitoba, Canada
Authors: Trommelen Michelle S. , Ross Martin
Published: January 2014

The distribution of basal drag zones (sticky spots) underneath palaeo‐ice streams or lobes is largely unknown. We investigated the centre of the large (300 km long and up to 400 km wide) deglacial Hayes Lobe in NE Manitoba, Canada, by focusing on surficial till and its composition to get insights into dispersal patterns and their potential relationships to areas of basal drag. Subglacial bed roughness is a good criterion to identify areas of basal drag, but till composition may provide important insights across smoother beds. The onset zone of the Hayes Lobe overlies Palaeozoic Carbonate Platform rocks, whereas the majority of the lobe overlies the low‐lying Canadian Shield. We show that, within a 3500‐km2 central area of this lobe, calcareous detritus within the till has been transported over 100 km within subglacial environments of reduced ice‐bed coupling and fast ice flow. Six per cent of samples (n = 782), however, outline 0.2 to 4 km wide spots with a dominantly local composition. The glacial history and composition indicate that the till within these spots contains high inheritance from a pre‐Late Wisconsinan ice‐flow phase, which we suggest was protected beneath sticky spots (low erosion, high strength) during transport of substantial calcareous detritus to the area. Furthermore, our findings show that local till spots are present within streamlined landforms, as well as till blankets or veneers over bedrock. This diverse geomorphology indicates that the process of drumlinization within the deglacial Hayes Lobe does not appear to have been responsible for significant sediment transport or deposition across the study area. The overall record thus indicates potentially complex spatiotemporal shifts between calcareous till deposition, sticky conditions, erosion and drumlinization – which supports the subglacial bed mosaic model.
Synthesis of Ranolazine Derivatives Containing the (1S,4S)‐2,5‐Diazabicyclo[2.2.1]Heptane Moiety and Their Evaluation as Vasodilating Agents
Authors: López‐Ortiz Manuel , Monsalvo Ivan , Demare Patricia , Paredes Cristina , Mascher Dieter , Hernández Carlos , Hernández Marcos , Regla Ignacio
Published: January 2014

Two diazabicyclic analogues of ranolazine, (S,S,S)‐5 and (S,S,R)‐5, and their epimeric mixture were synthesized. Furthermore, their vasomotor effects on rat aorta rings precontracted with phenylephrine were analyzed. These compounds showed vasodilating effects significantly greater than ranolazine. The vasodilating activities of these analogues have two components, one that depends on the endothelium, due to the release of NO, and another one due to a direct effect on the vascular smooth muscle. The compounds [(S,S,S)(S,S,R)]‐5 and (S,S,R)‐5 induce, in a manner similar to ranolazine, the release of a prostanoid from the cyclooxygenase pathway, whose vasoconstrictor effect is masked by the predominant vasodilation induced by these compounds.
Unraveling the Role of Arg4 and Arg6 in the Auto‐Inhibition Mechanism of GSK3β From Molecular Dynamics Simulation
Authors: Mou Linkai , Li Molin , Lu Shao‐Yong , Li Shuai , Shen Qiancheng , Zhang Jian , Li Chuangang , Lu Xuefeng
Published: January 2014

Glycogen synthase kinase 3β (GSK3β) is a multifunctional serine/threonine protein kinase that is involved in several biological processes including insulin and Wnt signaling pathways. GSK3β can be phosphorylated by the protein kinase B (PKB). The mutations of Arg4 and Arg6 to alanine at N‐terminal GSK3β have been reported to impair its ability to autophosphorylate at Ser9. Despite the extensive experimental observations, the detailed mechanism for the auto‐inhibition of GSK3β has not been rationalized at the molecular level. In this study, we have demonstrated the structural consequences of GSK3β R4A and R6A mutations and the atomic changes that influenced the loss of PKB‐binding affinity. Molecular dynamics simulation results suggested significant loss in atomic contacts in the R4A and R6A mutant systems compared to the wild‐type system. Furthermore, we observed many notable changes (such as conformation, residues motions, hydrogen bonds, and binding free energy) in the mutated GSK3β–PKB complexes. Loss of binding affinity in the mutated systems rendered the decrease in GSK3β phosphorylation, which, in turn, impaired the auto‐inhibition of GSK3β. The significant outcomes obtained from this study can explain the auto‐inhibition of GSK3β and maybe facilitate type 2 diabetes mellitus researches and in developing the potent drug therapies.
Design and Synthesis of a New Class of 4‐Aminoquinolinyl‐ and 9‐Anilinoacridinyl Schiff Base Hydrazones as Potent Antimalarial Agents
Authors: Sharma Moni , Chauhan Kuldeep , Srivastava Rajeev K. , Singh Shiv V. , Srivastava Kumkum , Saxena Jitendra K. , Puri Sunil K. , Chauhan Prem M. S.
Published: January 2014

A series of novel 4‐aminoquinolinyl and 9‐anilinoacridinyl Schiff base hydrazones have been synthesized and evaluated for their antimalarial activity. All compounds were evaluated in vitro for their antimalarial activity against chloroquine‐sensitive strain 3D7 and the chloroquine‐resistant K1 strain of Plasmodium falciparum and for cytotoxicity toward Vero cells. Compounds 17, 20, and 21 displayed good activity against the 3D7 strain with IC50 values ranging from 19.69 to 25.38 nm. Moreover, compounds 16, 17, 21, 24, 32, and 33 exhibited excellent activities (21.64–54.26 nm) against K1 strain and several compounds displayed β‐hematin inhibitory activity, suggesting that they act on the heme crystallization process such as CQ. Compounds were also found to be non‐toxic with good selectivity index.