bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of uncharged colloidal inclusions in polyelectrolyte hydrogels
Authors: MOHAMMADI ALIASGHAR , HILL REGHAN J.
Published: January 2011

We calculate the dynamics of an uncharged colloidal sphere embedded in a quenched polyelectrolyte hydrogel to (i) an oscillatory (optical and magnetic) force, as adopted in classical micro-rheology, and (ii) an oscillatory electric field, as adopted in electrical micro-rheology and electro-acoustics. The hydrogel is modelled as a linearly elastic porous medium with the charge fixed to the skeleton and saturated with a Newtonian electrolyte; and the colloidal inclusion is modelled as a rigid, impenetrable sphere. The dynamic micro-rheological susceptibility, defined as the ratio of the particle displacement to the strength of an applied oscillatory force, depends on the fixed-charge density and ionic strength and is bounded by the limits for incompressible and uncharged, compressible skeletons. Nevertheless, the influences of fixed charge and ionic strength vanish at frequencies above the reciprocal draining time, where the polymer and the electrolyte hydrodynamically couple as a single incompressible phase. Generally, the effects of fixed charge and ionic strength are small compared with, for example, the influences of polymer slip at the particle surface. The electrical susceptibility, defined as the ratio of the particle displacement to the strength of an applied oscillatory electric field, is directly influenced by charge at all frequencies, irrespective of skeleton compressibility. At low frequencies, polymer charge modulates the driving (electro-osmotic) and restoring (electrostatically enhanced elastic) forces, whereas charge has no influence on the restoring force at high frequencies where dilational strain is suppressed by hydrodynamic coupling with the electrolyte. In striking contrast to charged inclusions in uncharged hydrogels (Wang & Hill, J. Fluid Mech., vol. 640, 2009, pp. 357–400), the electrical susceptibility at high frequencies is independent of electrolyte concentration. Rather, the dynamics primarily reflect the elastic modulus, charge and hydrodynamic permeability, with a relatively weak dependence on particle size. Interestingly, the dynamic mobility in the zero-momentum reference frame, which is central to the electro-acoustic response, is qualitatively different from the dynamic mobility in the skeleton-fixed reference frame. Finally, we propose a phenomenological harmonic-oscillator model to address – in an approximate manner – the dynamics of charged particles in charged hydrogels. This shows that particle dynamics at low frequencies are dominated by particle charge, whereas high-frequency dynamics are dominated by hydrogel charge.
SEM description of the first larval instar ofAchelia assimilis(Pycnogonida: Ammotheidae)
Authors: Lehmann Tobias , Weinzierl Christa , Melzer Roland R.
Published: January 2011

The present paper is the first scanning electron microscope (SEM) description of a protonymphon larva of an Ammotheidae. The morphology of the first larval instar ofAchelia assimilisis described in detail and illustrated for the first time. The morphological characters are compared to previous larval descriptions of other pycnogonid species. The larvae are integrated into Bain's classification of larval types within the pycnogonids (Bain, 2003a) as a ‘typical protonymphon’. Larvae were obtained from ovigerous males, caught in Punta Huinay, Huinay, Chile and analysed with light microscope and SEM. Descriptions of pycnogonid protonymphons at a species-specific level in the future will contribute to a deeper understanding of larval pycnogonid taxonomy at the level of differential diagnoses.
New species of excavating sponges (Porifera: Demospongiae) on coral reefs from the Mexican Pacific Ocean
Authors: Cruz-Barraza José Antonio , Carballo José Luis , Bautista-Guerrero Eric , Nava Héctor
Published: January 2011

Three new species of coral reef boring sponges were found in remote coral reefs from Revillagigedo Island, an archipelago that is 386 km from the continent.Cliona medinaesp. nov. is a sponge with orange-yellow papillae characterized by short almost straight spirasters.Cliona tropicalissp. nov., is a yellow papillate sponge with a spicule complement similar to the species included in theCliona viridiscomplex. However, the new species differs from the rest of the species mainly in its external morphology and by differences in the size and shape of spicules.Thoosa purpureasp. nov. is characterized by its purple colour, and the spicular complement formed by tylostyles, two amphiaster categories, bi- tri- and tetra-radiate oxyasters and smooth or microspined centrotylote oxeas. In addition,Cliothosa tylostrongylatasp. nov. is also described from coral reefs from the southern Mexican Pacific Ocean. This is a light red species, with tylostyles and tylostrongyles as megascleres and ramose and nodulose amphiasters as microscleres. The four species were found exclusively excavating skeletons of live or dead corals of the genusPocillopora. This study increases the number of boring sponges known from the Mexican Pacific Ocean to 22 species and it is the first study on marine sponge fauna from the Revillagigedo archipelago.
Angiogenesis and parasitic helminth-associated neovascularization
Authors: DENNIS ROGER D. , SCHUBERT UWE , BAUER CHRISTIAN
Published: January 2011

Successful metazoan parasitism, among many other factors, requires a supply of nutrients and the removal of waste products. There is a prerequisite for a parasite-defined vasculature. The angiogenic mechanism(s) involved presumably depend on the characteristics of the tissue- and vascular system-dwelling, parasitic helminths. Simplistically, 2 possibilities or a combination of both have been considered in this review. The multifactorial induction of parasitic helminth-associated neovascularization could arise through, either a host-, a parasite- or a host-/parasite-dependent, angiogenic switch. Most studies appear to support the first and third hypotheses, but evidence exists for the intrahepatic cestodeEchinococcus multilocularis, the free-living nematodeCaenorhabditis elegansand the intravascular trematodeSchistosoma mansonifor the second inference. In contrast, the nematode anti-coagulant protein NAPc2 from adultAncylostoma caninumis also an anti-angiogenic factor.
Self-detection in robots: a method based on detecting temporal contingencies
Authors: Stoytchev Alexander
Published: January 2011

This paper addresses the problem of self-detection by a robot. The paper describes a methodology for autonomous learning of the characteristic delay between motor commands (efferent signals) and observed movements of visual stimuli (afferent signals). The robot estimates its own efferent-afferent delay from self-observation data gathered while performing motor babbling, i.e., random rhythmic movements similar to the primary circular reactions described by Piaget. After the efferent-afferent delay is estimated, the robot imprints on that delay and can later use it to successfully classify visual stimuli as either “self” or “other.” Results from robot experiments performed in environments with increasing degrees of difficulty are reported.
Realizing the promise of robotic self-x systems
Authors: Menezes Amor A. , Kabamba Pierre T.
Published: January 2011

Consider a robot trying to accomplish a mission in an unfamiliar, hostile, and dynamic environment. As the robot encounters a seemingly insurmountable obstacle, it quickly reconfigures itself into two smaller robots, and with the aid of a nearby puddle of water, these two robots conduct self-detection procedures to confirm successful reconfiguration. One robot then calibrates itself using its reduced sensor suite and begins climbing over the obstacle, whilst the other robot folds itself into a compact structure and finds a crevice it can use to bypass the obstacle. But when the obstacle shifts, both robots send signals to a base to warn of impending mission failure. A copy of the original robot, located at the base, receives these warning signals and initiates a rapid self-replication process by assembling available resources. The resultant robotic offspring are then ready to continue the mission when called upon.
Through the eye of a needle: the emergence of a practice-led research doctorate in music
Authors: Draper Paul , Harrison Scott
Published: January 2011

This paper explores recent developments in relation to doctoral research training in music. Drawing on the findings of a case-study of a recently established practice-led doctorate at an Australian conservatoire, we offer insights into the attributes of its expanding cohort. We interrogate a blended research training structure of academic supervision, coursework, web-based tools and administrative resources in order to reveal the obstacles to, and opportunities for improvement. The paper concludes by arguing programme design refinements which contribute to a deeper understanding of practice-led doctorates in music while inviting readers to similarly consider their own experiences.
Prosecuting the French: patterns of trials against French defendants in Valencia, 1566–1686
Authors: KNUTSEN GUNNAR W. , NAVARRO DANIEL MUÑOZ
Published: January 2011

A serial study of court records from two different jurisdictions in early modern Valencia shows that during the years 1566–1686 there was one single period with significantly higher numbers of trials against French defendants. This coincided with the period of the Spanish monarchy's greatest worries about outside influence in Spain. However, the increased number of trials is only traceable in one of the two courts under study, that of the Inquisition, which was under the control of the central government. The locally controlled court of criminal justice (Justicia) did not show any such increased activity against Frenchmen.
Participating is more important than winning: the impact of socio-economic change on commoners' participation in eighteenth- and nineteenth-century Flanders
Authors: DE MOOR TINE
Published: January 2011

In this article the participation profile of commoners of a Flemish case-study is reconstructed in order to identify their individual motivations for using the common, in some cases even becoming a manager of that common, in some cases only just claiming membership. Nominative linkages between membership lists, book-keeping accounts and regulatory documents of the common on the one hand and censuses and marriage acts on the other allow us to explain the behaviour of the commoners. It becomes clear why some decisions were taken – for example, to dissolve a well-functioning cattle-registration system – and how these affected the resource use of the common during the eighteenth and early nineteenth centuries. The analysis explains how internal shifts in power balances amongst groups of active users and those who did not have the means or willingness to participate could jeopardize the internal cohesion of the commoners as a group.
Excluded-volume potential for rigid molecules endowed with C2v symmetry
Authors: BISI F. , ROSSO R.
Published: January 2011

The excluded volume of a pair of molecules is proportional to the second virial coefficient in hard-core models that represent, for instance, the reference model in perturbation approaches to statistical theories of fluids [see, e.g. Chap. 5 of Kalikmanov, V. (2001), Statistical Physics of Fluids. Texts and Monograph in Physics, Springer, Berlin]. In three space dimensions, there exist exact results for convex molecules and in fact lack of convexity has been a major obstacle in applying the mathematical techniques employed in the convex case. In this paper, we illustrate how a mixed—analytical and numerical—method can be used to obtain exact expressions of the excluded volume for a pair of non-convex molecules conceived as aggregates of hard spheres; these can model van der Waals regions associated to the atoms forming each molecule. To compute the excluded volume for molecules endowed with C2v symmetry, modelled as chains of tangent hard spheres, we adapt a numerical code available to the scientific community. Because the result is a rather cumbersome expression in term of the relative orientation of the interacting molecules, we expand it over a suitable set of symmetry adapted Wigner functions to build up approximate, but faithful expressions, and we also prove analytical results announced elsewhere [Bisi, F., Durand, G., Rosso, R. & Virga, E. (2008), Polar steric interactions for v-shaped molecules. Phys. Rev. E, 78, 011705].
Heterosexual Political Science
Authors: Brettschneider Marla
Published: January 2011

Doing queer theory as political scientists enables us to approach central questions of the discipline in new and productive ways. This work makes possible innovative theoretical investigation of core concepts in political science such as power, justice, freedom, equality, and democracy. Queer theory can deepen the study of power by focusing on the lives, experiences, and institutions of GLBT people and communities. In the process, new frameworks are developed for the study of political theory more broadly. When done well, queer theory draws on the field's interdisciplinarity by bringing political scientists into conversation with other scholars on key matters that are best not bound by disciplinary borders. Similarly, queer theory at its best draws on the multiple perspectives developed in fields such as post-colonial, ethnic and critical race, feminist, class and ability, religious, and cultural studies.
The Study of Local Elections
Authors: Marschall Melissa , Shah Paru , Ruhil Anirudh
Published: January 2011

Given the large number of cases and considerable institutional and contextual variation across and within local governments, one might assume that the study of local elections is an area already well harvested by political scientists. The truth, however, is that this area of inquiry is relatively unexplored. In fact, to say that a field of study on local elections exists would be a bit of an overstatement. Not only is the literature rather small and not particularly cohesive, but the data collection and methods of analysis are also somewhat primitive, particularly compared to research on state and federal elections. While, on the one hand, this lack of subfield development means that there are many unanswered and even unexplored questions, on the other hand, it means that the possibilities for future research are practically limitless.
Political Behavior in the Context of Racial Diversity: The Case for Studying Local Politics
Authors: Kaufmann Karen M. , Rodriguez Antonio
Published: January 2011

Within contemporary political science, local elections are the perennial bridesmaids of behavioral research. While municipal contests are more numerous than any other type of election, academic interest in the factors that motivate local participation and voting behavior pales in comparison to the attention given to national politics. Case studies of individual elections in a small subset of larger American cities do exist, but within the local politics literature, few studies argue for a general theory of local voting behavior (but see Kaufmann 2004; Oliver and Ha 2007). Even in those cases that do, insufficient data exist to rigorously test or replicate these results on a large scale.
Political Science Careers at Comprehensive Universities: Building Balanced Careers at “Greedy” Institutions
Authors: Hendrickson Ryan C. , Mueller Melinda A. , Strand Jonathan R.
Published: January 2011

A considerable amount of research exists about political science careers at community colleges and liberal arts institutions, as well as about training and hiring practices across different types of institutions. However, there is virtually no commentary available on political science careers at comprehensive institutions, where a significant proportion of those in the field will spend their professional careers. The primary goal of this article is to initiate a conversation about working at a comprehensive university, which has both similarities to and important differences with Ph.D.-granting universities and liberal arts institutions. In doing so, we seek to highlight and discuss unique subtleties and complexities in the areas of teaching, research, and service that may provide insight into careers at comprehensive institutions and assist those who may be seeking or have just gained academic positions at such institutions.
Forty Years of Political Science in Europe: The European Consortium for Political Research Celebrates Its Ruby Anniversary
Authors: Bardi Luciano
Published: January 2011

In 2010, the European Consortium for Political Research (ECPR) celebrated its fortieth anniversary as the leading association for political science in Europe. Forty-one years earlier, in 1969, three European political scientists sent a letter to about a dozen of their European colleagues outlining some suggestions for creating an informal network of institutions and centers interested in comparative politics research. The authors of the letter were Serge Hurtig, Jean Blondel, and Stein Rokkan. Over the next year, led by Blondel and Rokkan with the support of a number of leading professors at the forefront of comparative research in their respective countries (the “founders” being Serge Hurtig, Norman Chester, Hans Daalder, Richard Rose, Jorgen Westerstahl, and Rudolf Wildenmann) and the backing of the Ford Foundation, the ECPR began to take shape. The original plan called for a European journal, a summer school, inventories of European political scientists and graduate courses, workshops, a data information center, and the construction of a transnational infrastructure of institutions to foster a self-sustaining community of professional political scientists. On July 29, 1970, a Ford Foundation grant was awarded to support the achievement of these aims, and the ECPR was established.
107th APSA Annual Meeting to Be Held in Seattle on “The Politics of Rights”
Authors: West Lauren G.
Published: January 2011

For the first time in its history, the Annual Meeting of the American Political Science Association will take place in Seattle, Washington. Set in a contemporary urban environment surrounded by the natural beauty of the Pacific Northwest, the 2011 Annual Meeting and Exhibition will offer something for everyone.
APSA Executive Director's Report, 2010
Authors: Brintnall Michael
Published: January 2011

The Executive Director's Report is an annual report on the state and activities of the association, and for 2010, the APSA remains vigorous and in good health. Programs across a very broad range of activities are going forward well, including the Africa Workshops, the Congressional Fellowship Program, the Centennial Center, ongoing task forces, new social networking capabilities, committee initiatives, the Teaching and Learning Conference, Annual Meeting siting and planning, coordinated work of 39 organized sections, departmental surveys and programming, and member services. This report is intended to provide an overview of the association's activities as they relate to promoting scholarship and teaching, connecting political science with the world, and supporting professional careers.
Reflected extended X-ray absorption fine structure study of the surface region of layered samples
Authors: Muñoz-Páez A. , López-Flores V. , Díaz-Moreno S. , Bowron D. T. , Ramos S. , Ansell S.
Published: January 2011

We present preliminary reflection extended X-ray absorption fine structure results on reactive magnetron sputtering molybdenum nitride (MoN) layered samples, with different compositions and surface layer thickness. The results obtained over a wide range of incidence angles show significant differences between two samples where the outer layer is either Mo metal or MoN.
Study of metallic pieces from the Andalusian baroque period with micro X-ray diffraction and micro X-ray fluorescence
Authors: Muñoz-Páez A. , Herrera L. K. , Justo A. , Sans J. A. , Martínez-Criado G.
Published: January 2011

Within the framework of a wide study of pieces of cultural heritage from the Andalusian baroque period, synchrotron radiation techniques were used to characterize the metallic parts of mirrors and musical organ pipes. By using X-ray fluorescence (XRF) and X-ray diffraction (XRD) with micrometre resolution information was obtained which was relevant either in the conservation or in the identification of these pieces. By monitoring with micro X-ray diffraction (μXRD) the degradation process of the amalgam of the mirrors, the evolution of the corrosion products could be followed. The identification and distribution of trace elements of tin and lead phases forming the organ metal pipes was carried out with the aid of micro X-ray fluorescence (μXRF). This technique allowed for the quantification of the elemental distributions in the major and minor components, knowledge useful to improve the manufacture of modern musical organs.
How does a star chain (nanooctopus) crawl through a nanopore?
Authors: Ge Hui , Pispas Stergios , Wu Chi
Published: January 2011

We found that for a f-arm star, the critical flow rate (qc,star) is related to both f and fin, depending on whether fin ≤ f/2 or ≥ f/2.
FLIPL induces caspase 8 activity in the absence of interdomain caspase 8 cleavage and alters substrate specificity
Authors: Pop Cristina , Oberst Andrew , Drag Marcin , Van Raam Bram J. , Riedl Stefan J. , Green Douglas R. , Salvesen Guy S.
Published: January 2011

Caspase 8 is an initiator caspase that is activated by death receptors to initiate the extrinsic pathway of apoptosis. Caspase 8 activation involves dimerization and subsequent interdomain autoprocessing of caspase 8 zymogens, and recently published work has established that elimination of the autoprocessing site of caspase 8 abrogates its pro-apoptotic function while leaving its proliferative function intact. The observation that the developmental abnormalities of caspase 8-deficient mice are shared by mice lacking the dimerization adapter FADD (Fas-associated death domain) or the caspase paralogue FLIPL [FLICE (FADD-like interleukin 1β-converting enzyme)-inhibitory protein, long form] has led to the hypothesis that FADD-dependent formation of heterodimers between caspase 8 and FLIPL could mediate the developmental role of caspase 8. In the present study, using an inducible dimerization system we demonstrate that cleavage of the catalytic domain of caspase 8 is crucial for its activity in the context of activation by homodimerization. However, we find that use of FLIPL as a partner for caspase 8 in dimerization-induced activation rescues the requirement for intersubunit linker proteolysis in both protomers. Moreover, before processing, caspase 8 in complex with FLIPL does not generate a fully active enzyme, but an attenuated species able to process only selected natural substrates. Based on these results we propose a mechanism of caspase 8 activation by dimerization in the presence of FLIPL, as well as a mechanism of caspase 8 functional divergence in apoptotic and non-apoptotic pathways.
TBC proteins: GAPs for mammalian small GTPase Rab?
Authors: Fukuda Mitsunori
Published: January 2011

The TBC (Tre-2/Bub2/Cdc16) domain was originally identified as a conserved domain among the tre-2 oncogene product and the yeast cell cycle regulators Bub2 and Cdc16, and it is now widely recognized as a conserved protein motif that consists of approx. 200 amino acids in all eukaryotes. Since the TBC domain of yeast Gyps [GAP (GTPase-activating protein) for Ypt proteins] has been shown to function as a GAP domain for small GTPase Ypt/Rab, TBC domain-containing proteins (TBC proteins) in other species are also expected to function as a certain Rab-GAP. More than 40 different TBC proteins are present in humans and mice, and recent accumulating evidence has indicated that certain mammalian TBC proteins actually function as a specific Rab-GAP. Some mammalian TBC proteins {e.g. TBC1D1 [TBC (Tre-2/Bub2/Cdc16) domain family, member 1] and TBC1D4/AS160 (Akt substrate of 160 kDa)} play an important role in homoeostasis in mammals, and defects in them are directly associated with mouse and human diseases (e.g. leanness in mice and insulin resistance in humans). The present study reviews the structure and function of mammalian TBC proteins, especially in relation to Rab small GTPases.
Rapid Reaction Kinetics: Lessons Learnt from Ion Pumps
Authors: Clarke Ronald J.
Published: January 2011

Chemical kinetics underwent a revolution in the 1950–60s with the development by Manfred Eigen of relaxation kinetic techniques and theory for the analysis of the results obtained. The techniques he introduced extended the time scale of measurable reactions into the microsecond range and beyond. Since then, computing power has increased astronomically. Some of the approximations traditionally used in the analysis of relaxation kinetic data to reduce mathematical complexity are, therefore, now no longer a necessity. Numerical integration of coupled series of differential rate equations can be performed in seconds or less on desk-top computers. In research on the mechanism of the Na+,K+-ATPase, it has been found that traditional approaches to relaxation kinetic data can sometimes lead to erroneous conclusions or to an incomplete description of the mechanism. Therefore, one needs to be flexible in one’s approach to kinetic data analysis and carefully consider the validity of any approximations used.
Development of Cubosomes as a Cell-Free Biosensing Platform
Authors: Fraser Scott J. , Dawson Raymond M. , Waddington Lynne J. , Muir Ben W. , Mulet Xavier , Hartley Patrick G. , Separovic Frances , Polyzos Anastasios
Published: January 2011

The parallel between the lipidic microenvironments of the inverse bicontinuous cubic phase and the biological membrane distinguishes cubic phases as an attractive option for development of cell-free biosensors containing protein or glycolipid receptors. Herein we describe a novel strategy toward the creation of a biosensing platform derived from the surface attachment of a colloidally stable inverse cubic structure (cubosomes). We report the preparation of cubosomes composed of the amphiphile phytantriol, the membrane glycolipid receptor monosialoganglioside-GM1 and the biotin-functionalized amphiphile 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[biotinyl(polyethyleneglycol)-2000] (bDSPE). The tethering of cubosomes to the various surfaces was mediated through bDSPE binding to streptavidin- and avidin-modified surfaces. Allylamine plasma polymer surface modification enhanced the surface immobilization of avidin, which increased the density of bound cubosomes. The resultant polymer–protein–cubosome complex was imaged by cryo-transmission electron microscopy analysis and the cubosome structure was impressively preserved within the complex. Cholera toxin binding to cubosomes containing GM1 was used to assess the performance of the cubosomes, subsequent to surface attachment, via a modified enzyme-linked immunosorbent assay. Specific immobilization of complex protein–receptor–cubosome systems paves the way for development of a structurally complex, heterogeneous platform for sensing applications.
Targeted delivery of a cisplatin prodrug for safer and more effective prostate cancer therapy in vivo
Authors: Dhar Shanta , Kolishetti Nagesh , Lippard Stephen J. , Farokhzad Omid C.
Published: January 2011

Targeted delivery and controlled release of inactive platinum (Pt) prodrugs may offer a new approach to improve the efficacy and tolerability of the Pt family of drugs, which are used to treat 50% of all cancers today. Using prostate cancer (PCa) as a model disease, we previously described the engineering of aptamer (Apt)-targeted poly(D,L-lactic-
co
-glycolic acid)-
b
-poly(ethylene glycol) (PLGA-
b
-PEG) nanoparticles (NPs) encapsulating a Pt(IV) prodrug
c
,
t
,
c
[Pt(NH
3
)
2
-(O
2
CCH
2
CH
2
CH
2
CH
2
CH
3
)
2
Cl
2
] (
1
) (Pt-PLGA-
b
-PEG-Apt-NP), which target the extracellular domain of the prostate specific membrane antigen (PSMA), for enhanced in vitro cytotoxicity. Here we demonstrate enhanced in vivo pharmacokinetics (PK), biodistribution, tolerability, and efficacy of Pt-PLGA-
b
-PEG-Apt-NP (150±15 nm encapsulating ∼5% wt/wt Pt(IV) prodrug) when compared to cisplatin administered in its conventional form in normal Sprague Dawley rats, Swiss Albino mice, and the PSMA-expressing LNCaP subcutaneous xenograft mouse model of PCa, respectively. The 10-d maximum tolerated dose following a single i.v. injection of Pt-PLGA-
b
-PEG-NP in rats and mice was determined at 40 mg/kg and 5 mg/kg, respectively. PK studies with Pt-PLGA-
b
-PEG-NP revealed prolonged Pt persistence in systemic blood circulation and decreased accumulation of Pt in the kidneys, a major target site of cisplatin toxicity. Pt-PLGA-
b
-PEG-Apt-NPs further displayed the significant dose-sparing characteristics of the drug, with equivalent antitumor efficacy in LNCaP xenografts at 1/3 the dose of cisplatin administered in its conventional form (0.3 mg/kg vs. 1 mg/kg). When considering the simultaneous improvement in tolerability and efficacy, the Pt-PLGA-
b
-PEG-Apt NP provides a remarkable improvement in the drug therapeutic index.
VHL
loss in renal cell carcinoma leads to up-regulation of CUB domain-containing protein 1 to stimulate PKCδ-driven migration
Authors: Razorenova Olga V. , Finger Elizabeth C. , Colavitti Renata , Chernikova Sophia B. , Boiko Alexander D. , Chan Charles K. F. , Krieg Adam , Bedogni Barbara , LaGory Edward , Weissman Irving L. , Broome-Powell Marianne , Giaccia Amato J.
Published: January 2011

A common genetic mutation found in clear cell renal cell carcinoma (CC-RCC) is the loss of the von Hippel-Lindau (
VHL
) gene, which results in stabilization of hypoxia-inducible factors (HIFs), and contributes to cancer progression and metastasis. CUB-domain-containing protein 1 (CDCP1) was shown to promote metastasis in scirrhous and lung adenocarcinomas as well as in prostate cancer. In this study, we established a molecular mechanism linking
VHL
loss to induction of the
CDCP1
gene through the HIF-1/2 pathway in renal cancer. Also, we report that Fyn, which forms a complex with CDCP1 and mediates its signaling to PKCδ, is a HIF-1 target gene. Mechanistically, we found that CDCP1 specifically regulates phosphorylation of PKCδ, but not of focal adhesion kinase or Crk-associated substrate. Signal transduction from CDCP1 to PKCδ leads to its activation, increasing migration of CC-RCC. Furthermore, patient survival can be stratified by CDCP1 expression at the cell surface of the tumor. Taken together, our data indicates that CDCP1 protein might serve as a therapeutic target for CC-RCC.
Structure, function and latency regulation of a bacterial enterotoxin potentially derived from a mammalian adamalysin/ADAM xenolog
Authors: Goulas Theodoros , Arolas Joan L. , Gomis-Rüth F. Xavier
Published: January 2011

EnterotoxigenicBacteroides fragilisis the most frequent disease-causing anaerobe in the intestinal tract of humans and livestock and its specific virulence factor is fragilysin, also known asB. fragilistoxin. This is a 21-kDa zinc-dependent metallopeptidase existing in three closely related isoforms that hydrolyze E-cadherin and contribute to secretory diarrhea, and possibly to inflammatory bowel disease and colorectal cancer. Here we studied the function and zymogenic structure of fragilysin-3 and found that its activity is repressed by a ∼170-residue prodomain, which is the largest hitherto structurally characterized for a metallopeptidase. This prodomain plays a role in both the latency and folding stability of the catalytic domain and it has no significant sequence similarity to any known protein. The prodomain adopts a novel fold and inhibits the protease domain via an aspartate-switch mechanism. The catalytic fragilysin-3 moiety is active against several protein substrates and its structure reveals a new family prototype within the metzincin clan of metallopeptidases. It shows high structural similarity despite negligible sequence identity to adamalysins/ADAMs, which have only been described in eukaryotes. Because no similar protein has been found outside enterotoxigenicB. fragilis, our findings support that fragilysins derived from a mammalian adamalysin/ADAM xenolog that was co-opted byB. fragilisthrough a rare case of horizontal gene transfer from a eukaryotic cell to a bacterial cell. Subsequently, this co-opted peptidase was provided with a unique chaperone and latency maintainer in the time course of evolution to render a robust and dedicated toxin to compromise the intestinal epithelium of mammalian hosts.
Lock-in thermo-electric detector arrays: thermal cross-talk prediction by non-linear model
Authors: Vandermeiren W , Stiens J , Shkerdin G , De Tandt C , Vounckx R
Published: January 2011

A non-linear numerical finite element method model of a thermo-electric focal plane array detector is presented here. Laser induced thermo-voltage profiles tend to spread out for small lock-in frequencies as the thermal diffusion length is inversely proportional to the square-root of the lock-in frequency. This leads to a frequency and spatial dependent thermal cross-talk level. In this paper we investigate the thermal cross-talk level quantitatively as a function of spatial coordinates and lock-in frequency. Experimental data are provided at an optical power level of 1 W. The impact of non-linear thermal parameters as the temperature dependence of the absorption coefficient, the thermal conductivity, the heat transfer coefficient and the Seebeck coefficient on the thermal profile and cross-talk level generated inside the detector material is studied in detail. Heat losses that are included in the model are conduction and laminar free convection. The relative importance of the above-mentioned non-linear thermal parameters in terms of thermal cross-talk for steady-state solutions is discussed as well.
Spatiotemporal regulations of Wee1 at the G2/M transition
Authors: Masuda Hirohisa , Fong Chii Shyang , Ohtsuki Chizuru , Haraguchi Tokuko , Hiraoka Yasushi
Published: January 2011

Wee1 is a protein kinase that negatively regulates mitotic entry in G2 phase by suppressing cyclin B–Cdc2 activity, but its spatiotemporal regulations remain to be elucidated. We observe the dynamic behavior of Wee1 in Schizosaccharomyces pombe cells and manipulate its localization and kinase activity to study its function. At late G2, nuclear Wee1 efficiently suppresses cyclin B–Cdc2 around the spindle pole body (SPB). During the G2/M transition when cyclin B–Cdc2 is highly enriched at the SPB, Wee1 temporally accumulates at the nuclear face of the SPB in a cyclin B–Cdc2-dependent manner and locally suppresses both cyclin B–Cdc2 activity and spindle assembly to counteract a Polo kinase–dependent positive feedback loop. Then Wee1 disappears from the SPB during spindle assembly. We propose that regulation of Wee1 localization around the SPB during the G2/M transition is important for proper mitotic entry and progression.
The muramidase EtgA from enteropathogenic Escherichia coli is required for efficient type III secretion
Authors: García-Gómez Elizabeth , Espinosa Norma , de la Mora Javier , Dreyfus Georges , González-Pedrajo Bertha
Published: January 2011

EnteropathogenicEscherichia coli(EPEC) is an important cause of infectious diarrhoea. It colonizes human intestinal epithelial cells by delivering effector proteins into the host cell cytoplasm via a type III secretion system (T3SS) encoded within the chromosomal locus of enterocyte effacement (LEE). The LEE pathogenicity island also encodes a lytic transglycosylase (LT) homologue named EtgA. In the present work we investigated the significance of EtgA function in type III secretion (T3S). Purified recombinant EtgA was found to have peptidoglycan lytic activityin vitro. Consistent with this function, signal peptide processing and bacterial cell fractionation revealed that EtgA is a periplasmic protein. EtgA possesses the conserved glutamate characteristic of the LT family, and we show here that it is essential for enzymic activity. Overproduction of EtgA in EPEC inhibits bacterial growth and induces cell lysis unless the predicted catalytic glutamate is mutated. AnetgAmutant is attenuated for T3S, red blood cell haemolysis and EspA filamentation. BfpH, a plasmid-encoded putative LT, was not able to functionally replace EtgA. Overall, our results indicate that the muramidase activity of EtgA is not critical but makes a significant contribution to the efficiency of the T3S process.
Production of Complex Multiantennary N-Glycans in Nicotiana benthamiana Plants
Authors: Nagels Bieke , Van Damme Els J.M. , Pabst Martin , Callewaert Nico , Weterings Koen
Published: January 2011

In recent years, plants have been developed as an alternative expression system to mammalian hosts for the production of therapeutic proteins. Many modifications to the plant glycosylation machinery have been made to render it more human because of the importance of glycosylation for functionality, serum half-life, and the safety profile of the expressed proteins. These modifications include removal of plant-specific β1,2-xylose and core α1,3-fucose, and addition of bisecting N-acetylglucosamine, β1,4-galactoses, and sialic acid residues. Another glycosylation step that is essential for the production of complex human-type glycans is the synthesis of multiantennary structures, which are frequently found on human N-glycans but are not generated by wild-type plants. Here, we report both the magnICON-based transient as well as stable introduction of the α1,3-mannosyl-β1,4-N-acetylglucosaminyltransferase (GnT-IV isozymes a and b) and α1,6-mannosyl-β1,6-N-acetylglucosaminyltransferase (GnT-V) in Nicotiana benthamiana plants. The enzymes were targeted to the Golgi apparatus by fusing their catalytic domains to the plant-specific localization signals of xylosyltransferase and fucosyltransferase. The GnT-IV and -V modifications were tested in the wild-type background, but were also combined with the RNA interference-mediated knockdown of β1,2-xylosyltransferase and α1,3-fucosyltransferase. Results showed that triantennary Gn[GnGn] and [GnGn]Gn N-glycans could be produced according to the expected activities of the respective enzymes. Combination of the two enzymes by crossing stably transformed GnT-IV and GnT-V plants showed that up to 10% tetraantennary [GnGn][GnGn], 25% triantennary, and 35% biantennary N-glycans were synthesized. All transgenic plants were viable and showed no aberrant phenotype under standard growth conditions.
Unifying cluster-based structure models of decagonal Al–Co–Ni, Al–Co–Cu and Al–Fe–Ni
Authors: Deloudi Sofia , Fleischer Frank , Steurer Walter
Published: January 2011

The geometrical building principles of Al-based decagonal quasicrystals and their approximants are discussed from a cluster-based approach. Our investigations cover 11 modifications with two- or four-layer periodicity in the systems Al–Co–Ni, Al–Co–Cu and Al–Fe–Ni. We identified a cluster that leads to a unifying view of all these phases. This unit cluster has ∼ 20 Å diameter, four-layer periodicity along its tenfold axis and rod symmetry group p \overline{10}2m. The models obtained are in agreement with all the electron-density maps and electron-microscopy images available.
DNA glycosylase encoded by MUTYH functions as a molecular switch for programmed cell death under oxidative stress to suppress tumorigenesis
Authors: Oka Sugako , Nakabeppu Yusaku
Published: January 2011

8‐oxoguanine is a major base lesion in DNA or in nucleotides caused by oxidative stress, and is highly mutagenic because it can pair with adenine as well as cytosine. Adenine DNA glycosylase, encoded by the human mutY homolog gene, MUTYH, excises adenine in the nascent strand when inserted opposite 8‐oxoguanine in template DNA, and thus suppresses mutagenesis caused by 8‐oxoguanine that has accumulated in DNA due to oxidative stress. Several germ‐line mutations in MUTYH are predisposed to MUTYH‐associated polyposis, an autosomal recessive disorder characterized by multiple colorectal adenomas and carcinomas. Loss of function of MUTYH leads to an accumulation of somatic mutations in APC and KRAS genes, resulting in the development of adenomas/carcinomas. We recently demonstrated that accumulation of 8‐oxoguanine in nuclear and mitochondrial DNA triggers two distinct cell death pathways that are independent of each other. Both pathways are initiated by the accumulation of MUTYH‐generated single‐strand breaks (SSBs) in nuclear or mitochondrial DNA. Our findings indicate that MUTYH‐induced cell death due to oxidative stress results in an efficient elimination of mutagenic cells that have accumulated high levels of 8‐oxoguanine in their DNAs. It is most likely that loss of function of MUTYH in stem or progenitor cells in the intestinal epithelium of MUTYH‐associated polyposis patients results in escape from programmed cell death; however, accumulated 8‐oxoguanine causes various mutations in APC or KRAS genes in these proliferative cells, thereby promoting tumorigenesis. We thus propose that MUTYH suppresses tumorigenesis under conditions of oxidative stress by inducing cell death and by suppressing mutagenesis. (Cancer Sci 2011; 102: 677–682)
Peri‐operative anaphylaxis
Authors: Nel Linda , Eren Efrem
Published: January 2011

Peri‐operative anaphylaxis is an important cause for mortality and morbidity associated with anaesthesia. The true incidence is unknown and is most likely under reported. Diagnosis can be difficult, particularly as a number of drugs are given simultaneously and any of these agents can potentially cause anaphylaxis. This review covers the clinical features, differential diagnosis and management of anaphylaxis associated with anaesthesia. The investigations to confirm the clinical suspicion of anaphylaxis and further tests to identify the likely drug(s) are examined. Finally the salient features of common and rare causes including non‐drug substances are described.
Anti-thymoglobulin (ATG) treatment does not reverse type 1 diabetes in the acute virally induced rat insulin promoter-lymphocytic choriomeningitis virus (RIP-LCMV) model
Authors: Bresson D , von Herrath M G
Published: January 2011

Immune modulators such as anti-thymoglobulin (ATG) are under clinical evaluation for the treatment of type 1 diabetes (T1D). Although such agents have cured T1D in the non-obese diabetic (NOD) model, their clinical efficacy has been much lower. In order to improve the odds of successful translation from bench to bedside, we propose to evaluate this agent under more stringent conditions. Here, we evaluated the capacity of ATG to reverse T1D in the acute rat insulin promoter-lymphocytic choriomeningitis virus (RIP-LCMV) model. RIP-LCMV-glycoprotein (GP) mice were treated after new-onset T1D with murine ATG antibodies. Although ATG treatment did not impair viral clearance it failed to reverse new-onset T1D in this model. The CD4 : CD8 ratio was reduced drastically upon LCMV infection due to an expansion of CD8 effectors but ameliorated in ATG-treated mice. Although the percentage of CD4+CD25+ regulatory T cells (Tregs) within the CD4+ population was increased significantly after ATG therapy, their frequency in the periphery was reduced dramatically and never returned to normal baseline. The inability of ATG treatment to cure T1D in a stringent viral model (RIP-LCMV mice) is due at least partially to the inability to maintain or increase a sufficient CD4+CD25+ Tregs frequency, in striking contrast with what was reported in the NOD model. Our data would argue for the use of multiple animal models to assess efficacy of promising immune-based interventions and select the most potent therapies for future clinical trials.
Alleviating psychological distress of suicide survivors: evaluation of a volunteer care programme
Authors: LU Y‐J. , CHANG H‐J. , TUNG Y‐Y. , HSU M‐C. , LIN M‐F.
Published: January 2011

Accessible summary

A supervised volunteer programme can provide safe care for suicide survivors.

Compared with newly trained volunteers, volunteers with at least 1 year of experience are more effective with suicide survivors with greater psychological distress.

Changes in psychological distress of suicide survivors occur after 2 months.

The crisis level in the worldwide suicide rate has revealed a severe suicide problem in Taiwan that is now well above the world average of 16 per 100 000 individuals. Many countries have relied on suicide care volunteers training programmes to conduct suicide prevention programmes. However, there is a dearth of research evaluating the effect of volunteers on psychological distress and the impact of volunteer experience level. An evaluation of the impact of experienced and novice volunteers in alleviating psychological distress of suicide survivors was conducted. A supervised programme trained 15 volunteers at Years 1 and 2. Year 1 volunteers completed 400 h of service with continuing education. Programme evaluation occurred after Year 2 volunteers had completed training. Eighty‐two suicide survivors were recruited. With 60 suicide survivors completing 3 month of volunteer care, a significant group difference with time interaction in suicide survivors who exhibited moderate to severe distress between the veteran care and novice care groups was found. Compared with novice volunteers, veteran volunteers with at least 1 year of experience are more effective with suicide survivors reporting higher psychological distress.
Chlorinated phenols control the expression of the multidrug resistance efflux pump MexAB–OprM in Pseudomonas aeruginosa by interacting with NalC
Authors: Ghosh Sudeshna , Cremers Claudia M. , Jakob Ursula , Love Nancy G.
Published: January 2011

NalC is a TetR type regulator that represses the multidrug efflux pump MexAB–OprM in Pseudomonas aeruginosa. Here we explain the mechanism of NalC‐mediated regulation of MexAB–OprM. We show that NalC non‐covalently binds chlorinated phenols and chemicals containing chlorophenol side‐chains such as triclosan. NalC‐chlorinated phenol binding results in its dissociation from promoter DNA and upregulation of NalC's downstream targets, including the MexR antirepressor ArmR. ArmR upregulation and MexR–ArmR complex formation have previously been shown to upregulate MexAB–OprM. In vivo mexB and armR expression analyses were used to corroborate in vitro NalC‐chlorinated phenol binding. We also show that the interaction between chlorinated phenols and NalC is reversible, such that removal of these chemicals restored NalC promoter DNA binding. Thus, the NalC‐chlorinated phenol interaction is likely a pertinent physiological mechanism that P. aeruginosa uses to control expression of the MexAB–OprM efflux pump.
Structural determinants for membrane insertion, pore formation and translocation ofClostridium difficiletoxin B
Authors: Genisyuerek Selda , Papatheodorou Panagiotis , Guttenberg Gregor , Schubert Rolf , Benz Roland , Aktories Klaus
Published: January 2011

Clostridium difficiletoxins A and B bind to eukaryotic target cells, are endocytosed and then deliver their N‐terminal glucosyltransferase domain after processing into the cytosol. Whereas glucosyltransferase, autoprocessing and cell‐binding domains are well defined, structural features involved in toxin delivery are unknown. Here, we studied structural determinants that define membrane insertion, pore formation and translocation of toxin B. Deletion analyses revealed that a large region, covering amino acids 1501–1753 of toxin B, is dispensable for cytotoxicity in Vero cells. Accordingly, a chimeric toxin, consisting of amino acids 1–1550 and the receptor‐binding domain of diphtheria toxin, caused cytotoxic effects. A large N‐terminal part of toxin B (amino acids 1–829) was not essential for pore formation (measured by86Rb+release in mammalian cells). Studies using C‐terminal truncation fragments of toxin B showed that amino acid residues 1–990 were still capable of inducing fluorescence dye release from large lipid vesicles and led to increased electrical conductance in black lipid membranes. Thereby, we define the minimal pore‐forming region of toxin B within amino acid residues 830 and 990. Moreover, we identify within this region a crucial role of the amino acid pair glutamate‐970 and glutamate‐976 in pore formation of toxin B.