bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational Nanoscience
Authors: Challacombe William , Chelikowsky Jim , Grossman Jeffrey , Krasheninnikov Arkady V. , Naumkin Fedor Y. , Schatz George C. , Seifert Gotthard , Singh Jayant K , Wales David , Wilson Mark , Fortunelli Alessandro , Sanvito Stefano , Heggie Malcolm , Zurek Eva ,   Royal Society of Chemistry
Published: June 2011

Nanoscience is one of the most exciting areas of modern physical science as it encompasses a range of techniques rather than a single discipline. It stretches across the whole spectrum of science including: medicine and health, physics, engineering and chemistry. Providing a deep understanding of the behaviour of matter at the scale of individual atoms and molecules, it provides a crucial step towards future applications of nanotechnology. The remarkable improvements in both theoretical methods and computational techniques make it possible for modern computational nanoscience to achieve a new level of chemical accuracy. It is now a discipline capable of leading and guiding experimental efforts rather than just following others. Computational Nanoscience addresses modern challenges in computational science, within the context of the rapidly evolving field of nanotechnology. It satisfies the need for a comprehensive, yet concise and up-to-date, survey of new developments and applications presented by the world's leading academics. It documents major, recent advances in scientific computation, mathematical models and theory development that specifically target the applications in nanotechnology. Suitable for theoreticians, researchers and students, the book shows readers what computational nanoscience can achieve, and how it may be applied in their own work. The twelve chapters cover topics including the concepts behind recent breakthroughs, the development of cutting edge simulation tools, and the variety of new applications.
An anti-Aβ (amyloid β) single-chain variable fragment prevents amyloid fibril formation and cytotoxicity by withdrawing Aβ oligomers from the amyloid pathway
Authors: Marín-Argany Marta , Rivera-Hernández Geovanny , Martí Joaquim , Villegas Sandra
Published: June 2011

Aβ (amyloid β) immunotherapy has been revealed as a possible tool in Alzheimer's disease treatment. In contrast with complete antibodies, the administration of scFvs (single-chain variable fragments) produces neither meningoencephalitis nor cerebral haemorrhage. In the present study, the recombinant expression of scFv-h3D6, a derivative of an antibody specific for Aβ oligomers, is presented, as well as the subsequent proof of its capability to recover the toxicity induced by the Aβ1–42 peptide in the SH-SY5Y neuroblastoma cell line. To gain insight into the conformational changes underlying the prevention of Aβ toxicity by this antibody fragment, the conformational landscape of scFv-h3D6 upon temperature perturbation is also described. Heating the native state does not lead to any extent of unfolding, but rather directly to a β-rich intermediate state which initiates an aggregation pathway. This aggregation pathway is not an amyloid fibril pathway, as is that followed by the Aβ peptide, but rather a worm-like fibril pathway which, noticeably, turns out to be non-toxic. On the other hand, this pathway is thermodynamically and kinetically favoured when the scFv-h3D6 and Aβ1–42 oligomers form a complex in native conditions, explaining how the scFv-h3D6 withdraws Aβ1–42 oligomers from the amyloid pathway. To our knowledge, this is the first description of a conformational mechanism by which a scFv prevents Aβ-oligomer cytotoxicity.
FAT/CD36 is located on the outer mitochondrial membrane, upstream of long-chain acyl-CoA synthetase, and regulates palmitate oxidation
Authors: Smith Brennan K. , Jain Swati S. , Rimbaud Stéphanie , Dam Aaron , Quadrilatero Joe , Ventura-Clapier Renée , Bonen Arend , Holloway Graham P.
Published: June 2011

FAT/CD36 (fatty acid translocase/Cluster of Differentiation 36), a plasma membrane fatty-acid transport protein, has been found on mitochondrial membranes; however, it remains unclear where FAT/CD36 resides on this organelle or its functional role within mitochondria. In the present study, we demonstrate, using several different approaches, that in skeletal muscle FAT/CD36 resides on the OMM (outer mitochondrial membrane). To determine the functional role of mitochondrial FAT/CD36 in this tissue, we determined oxygen consumption rates in permeabilized muscle fibres in WT (wild-type) and FAT/CD36-KO (knockout) mice using a variety of substrates. Despite comparable muscle mitochondrial content, as assessed by unaltered mtDNA (mitochondrial DNA), citrate synthase, β-hydroxyacyl-CoA dehydrogenase, cytochrome c oxidase complex IV and respiratory capacities [maximal OXPHOS (oxidative phosphorylation) respiration] in WT and KO mice, palmitate-supported respiration was 34% lower in KO animals. In contrast, palmitoyl-CoA-supported respiration was unchanged. These results indicate that FAT/CD36 is key for palmitate-supported respiration. Therefore we propose a working model of mitochondrial fatty-acid transport, in which FAT/CD36 is positioned on the OMM, upstream of long-chain acyl-CoA synthetase, thereby contributing to the regulation of mitochondrial fatty-acid transport. We further support this model by providing evidence that FAT/CD36 is not located in mitochondrial contact sites, and therefore does not directly interact with carnitine palmitoyltransferase-I as original proposed.
Identification and characterization of interactions between abscisic acid and mitochondrial adenine nucleotide translocators
Authors: Kharenko Olesya A. , Boyd Jason , Nelson Ken M. , Abrams Suzanne R. , Loewen Michele C.
Published: June 2011

ABA (abscisic acid) is a plant hormone involved in important processes including development and stress responses. Recent reports have identified a number of plant ABA receptors and transporters, highlighting novel mechanisms of ABA action. In the present paper we describe application of a chemical proteomics approach leading to the identification of mitochondrial ANTs (adenine nucleotide translocators) as ABA-interacting proteins. Initial in vitro studies confirmed inhibition of ANT-dependent ATP translocation by ABA. Further analysis demonstrated ANT-dependent uptake of ABA into both recombinant Arabidopsis thaliana ANT2-containing proteoliposomes and native isolated spinach mitochondria; the latter with a Km of 3.5 μM and a Vmax of 2.5 nmol/min per g of protein. ATP was found to inhibit ANT-dependent ABA translocation. Specificity profiles highlight the possibility of mechanistic differences in translocation of ABA and ATP. Finally, ABA was shown to stimulate ATPase activity in spinach mitochondrial extracts. ABA concentrations in plant cells are estimated to reach the low micromolar range during stress responses, supporting potential physiological relevance of these in vitro findings. Overall, the present in vitro work suggests the possibility of as yet uncharacterized mechanisms of ABA action in planta related to inhibition of mitochondrial ATP translocation and functional localization of ABA in the mitochondrial matrix.
Manifold effects of palmitoylcarnitine on endoplasmic reticulum metabolism: 11β-hydroxysteroid dehydrogenase 1, flux through hexose-6-phosphate dehydrogenase and NADPH concentration
Authors: Wang Xudong , Mick Gail J. , Maser Edmund , McCormick Kenneth
Published: June 2011

With the exception of the oxidation of G6P (glucose 6-phosphate) by H6PDH (hexose-6-phosphate dehydrogenase), scant information is available about other endogenous substrates affecting the redox state or the regulation of key enzymes which govern the ratio of the pyridine nucleotide NADPH/NADP. In isolated rat liver microsomes, NADPH production was increased, as anticipated, by G6P; however, this was strikingly amplified by palmitoylcarnitine. Subsequent experiments revealed that the latter compound, well within its physiological concentration range, inhibited 11β-HSD1 (11β-hydroxysteroid dehydrogenase 1), the bidirectional enzyme which interconnects inactive 11-oxo steroids and their active 11-hydroxy derivatives. Notably, palmitoylcarnitine also stimulated the antithetical direction of 11β-HSD1 reductase, namely dehydrogenase. This stimulation of H6PDH may have likewise contributed to the NADPH accretion. All told, the result of these enzyme modifications is, in a conjoint fashion, a sharp amplification of microsomal NADPH production. Neither the purified 11β-HSD1 nor that obtained following microsomal sonification were sensitive to palmitoylcarnitine inhibition. This suggests that the long-chain amphipathic acylcarnitines, given their favourable partitioning into the membrane lipid bilayer, disrupt the proficient kinetic and physical interplay between 11β-HSD1 and H6PDH. Finally, although IDH (isocitrate dehydrogenase) and malic enzyme are present in microsomes and increase NADPH concentration akin to that of G6P, neither had an effect on 11β-HSD1 reductase, evidence that the NADPH pool in the endoplasmic reticulum shared by the H6PDH/11β-HSD1 alliance is uncoupled from that governed by IDH and malic enzyme.
The RNA-binding protein HuR stabilizes survivin mRNA in human oesophageal epithelial cells
Authors: Donahue James M. , Chang Elizabeth T. , Xiao Lan , Wang Peng-Yuan , Rao Jaladanki N. , Turner Douglas J. , Wang Jian-Ying , Battafarano Richard J.
Published: June 2011

Overexpression of survivin, a member of the IAP (inhibitor of apoptosis) family, has been correlated with poorer outcomes in multiple malignancies, including oesophageal cancer. The regulatory mechanisms, particularly at the post-transcriptional level, involved in survivin overexpression are not well understood. Previous work from our group has shown that the RNA-binding protein HuR (Hu antigen R), which is also overexpressed in several malignancies, stabilizes the mRNA of XIAP (X-linked IAP), another IAP family member. In the present study, we demonstrate the binding of HuR to a 288 bp fragment in the 3′-UTR (untranslated region) of survivin mRNA in human oesophageal epithelial cells. Unexpectedly, overexpression of HuR led to a decrease in survivin expression. This was associated with decreased survivin mRNA and promoter activity, suggesting a decrease in transcription. Levels of p53, a negative transcriptional regulator of survivin, increased following HuR overexpression, in conjunction with enhanced p53 mRNA stability. Silencing p53 prior to HuR overexpression resulted in increased survivin protein and mRNA stability. These results demonstrate that, in the absence of p53, HuR overexpression results in increased survivin mRNA stability and protein expression. This provides an additional explanation for the increased survivin expression observed in oesophageal cancer cells that have lost p53.
Vesicle trafficking and membrane remodelling in cytokinesis
Authors: Neto Hélia , Collins Louise L. , Gould Gwyn W.
Published: June 2011

All cells complete cell division by the process of cytokinesis. At the end of mitosis, eukaryotic cells accurately mark the site of division between the replicated genetic material and assemble a contractile ring comprised of myosin II, actin filaments and other proteins, which is attached to the plasma membrane. The myosin–actin interaction drives constriction of the contractile ring, forming a cleavage furrow (the so-called ‘purse-string’ model of cytokinesis). After furrowing is completed, the cells remain attached by a thin cytoplasmic bridge, filled with two anti-parallel arrays of microtubules with their plus-ends interdigitating in the midbody region. The cell then assembles the abscission machinery required for cleavage of the intercellular bridge, and so forms two genetically identical daughter cells. We now know much of the molecular detail of cytokinesis, including a list of potential genes/proteins involved, analysis of the function of some of these proteins, and the temporal order of their arrival at the cleavage site. Such studies reveal that membrane trafficking and/or remodelling appears to play crucial roles in both furrowing and abscission. In the present review, we assess studies of vesicular trafficking during cytokinesis, discuss the role of the lipid components of the plasma membrane and endosomes and their role in cytokinesis, and describe some novel molecules implicated in cytokinesis. The present review covers experiments performed mainly on tissue culture cells. We will end by considering how this mechanistic insight may be related to cytokinesis in other systems, and how other forms of cytokinesis may utilize similar aspects of the same machinery.
Binding of chloroplast signal recognition particle to a thylakoid membrane protein substrate in aqueous solution and delineation of the cpSRP43–substrate interaction domain
Authors: Cain Peter , Holdermann Iris , Sinning Irmgard , Johnson Arthur E. , Robinson Colin
Published: June 2011

A cpSRP [chloroplast SRP (signal recognition particle)] comprising cpSRP54 and cpSRP43 subunits mediates the insertion of light-harvesting proteins into the thylakoid membrane. We dissected its interaction with a full-length membrane protein substrate in aqueous solution by insertion of site-specific photo-activatable cross-linkers into in vitro-synthesized Lhcb1 (major light-harvesting chlorophyll-binding protein of photosystem II). We show that Lhcb1 residues 166–176 cross-link specifically to the cpSRP43 subunit. Some cross-link positions within Lhcb1 are in the ‘L18’ peptide required for targeting of cpSRP substrates, whereas other cross-linking positions define a new targeting signal in the third transmembrane span. Lhcb1 was not found to cross-link to cpSRP54 at any position, and cross-linking to cpSRP43 is unaffected by the absence of cpSRP54. cpSRP43 thus effectively binds substrates autonomously, and its ability to independently bind an extended 20+-residue substrate region highlights a major difference with other SRP types where the SRP54 subunit binds to hydrophobic target sequences. The results also show that cpSRP43 can bind to a hydrophobic, three-membrane span, substrate in aqueous solution, presumably reflecting a role for cpSRP in the chloroplast stroma. This mode of action, and the specificity of the cpSRP43–substrate interaction, may be associated with cpSRP's unique post-translational mode of action.
ATP binding to the ϵ subunit of thermophilic ATP synthase is crucial for efficient coupling of ATPase and H+ pump activities
Authors: Kadoya Fumitaka , Kato Shigeyuki , Watanabe Kei , Kato-Yamada Yasuyuki
Published: June 2011

ATP binding to the ϵ subunit of F1-ATPase, a soluble subcomplex of TFoF1 (FoF1-ATPase synthase from the thermophilic Bacillus strain PS3), affects the regulation of F1-ATPase activity by stabilizing the compact, ATPase-active, form of the ϵ subunit [Kato, S., Yoshida, M. and Kato-Yamada, Y. (2007) J. Biol. Chem. 282, 37618–37623]. In the present study, we report how ATP binding to the ϵ subunit affects ATPase and H+ pumping activities in the holoenzyme TFoF1. Wild-type TFoF1 showed significant H+ pumping activity when ATP was used as the substrate. However, GTP, which bound poorly to the ϵ subunit, did not support efficient H+ pumping. Addition of small amounts of ATP to the GTP substrate restored coupling between GTPase and H+ pumping activities. Similar uncoupling was observed when TFoF1 contained an ATP-binding-deficient ϵ subunit, even with ATP as a substrate. Further analysis suggested that the compact conformation of the ϵ subunit induced by ATP binding was required to couple ATPase and H+ pumping activities in TFoF1 unless the ϵ subunit was in its extended-state conformation. The present study reveals a novel role of the ϵ subunit as an ATP-sensitive regulator of the coupling of ATPase and H+ pumping activities of TFoF1.
Me, Myself, and I: Different Recognition Rates for Three Photo-IDs of the Same Person
Authors: Bindemann Markus , Sandford Adam
Published: June 2011

In all contemporary societies, photo-identity documents are used routinely for person identification, but this process is surprisingly fallible. Here we show that this problem is not limited to the identification of specific photographs of a person, but transcends three identity cards of the same person with different images. These identity cards varied substantially from each other in how well they could be recognised but identification rates were generally poor. We also present a potential solution to this problem by demonstrating that person identification can be improved when several photographs of the same person are made available.
Prestimulus theta activity predicts correct source memory retrieval
Authors: Addante Richard J. , Watrous Andrew J. , Yonelinas Andrew P. , Ekstrom Arne D. , Ranganath Charan
Published: June 2011

Recent evidence indicates that the processing of a stimulus can be influenced by preceding patterns of brain activity. Here we examine whether prestimulus oscillatory brain activity can influence the ability to retrieve episodic memories. Neural activity in the theta-frequency band (4–8 Hz) was enhanced before presentation of test items which elicited accurate recollection of contextual details of the prior study episode (“source retrieval”), relative to trials for which item recognition was successful but source retrieval failed. Poststimulus theta activity was also related to source retrieval, and the magnitude of poststimulus theta was predicted by the magnitude of the prestimulus theta effects. The results suggest that ongoing neural processes occurring before stimulus onset might play a critical role in readying the brain for successful memory retrieval.
Tudor domain containing 7
(
Tdrd7
) is essential for dynamic ribonucleoprotein (RNP) remodeling of chromatoid bodies during spermatogenesis
Authors: Tanaka Takashi , Hosokawa Mihoko , Vagin Vasily V. , Reuter Michael , Hayashi Eri , Mochizuki Ayako L. , Kitamura Kouichi , Yamanaka Hidenori , Kondoh Gen , Okawa Katsuya , Kuramochi-Miyagawa Satomi , Nakano Toru , Sachidanandam Ravi , Hannon Gregory J. , Pillai Ramesh S. , Nakatsuji Norio , Chuma Shinichiro
Published: June 2011

In the male germline in mammals, chromatoid bodies, a specialized assembly of cytoplasmic ribonucleoprotein (RNP), are structurally evident during meiosis and haploidgenesis, but their developmental origin and regulation remain elusive. The tudor domain containing proteins constitute a conserved class of chromatoid body components. We show that
tudor domain containing 7
(
Tdrd7
), the deficiency of which causes male sterility and age-related cataract (as well as glaucoma), is essential for haploid spermatid development and defines, in concert with
Tdrd6
, key biogenesis processes of chromatoid bodies. Single and double knockouts of
Tdrd7
and
Tdrd6
demonstrated that these spermiogenic
tudor
genes orchestrate developmental programs for ordered remodeling of chromatoid bodies, including the initial establishment, subsequent RNP fusion with ubiquitous processing bodies/GW bodies and later structural maintenance.
Tdrd7
suppresses
LINE1
retrotransposons independently of piwi-interacting RNA (piRNA) biogenesis wherein
Tdrd1
and
Tdrd9
operate, indicating that distinct
Tdrd
pathways act against retrotransposons in the male germline.
Tdrd6
, in contrast, does not affect retrotransposons but functions at a later stage of spermiogenesis when chromatoid bodies exhibit aggresome-like properties. Our results delineate that chromatoid bodies assemble as an integrated compartment incorporating both germline and ubiquitous features as spermatogenesis proceeds and that the conserved
tudor
family genes act as master regulators of this unique RNP remodeling, which is genetically linked to the male germline integrity in mammals.
A model of cytoplasmically driven microtubule-based motion in the single-celled
Caenorhabditis elegans
embryo
Authors: Shinar Tamar , Mana Miyeko , Piano Fabio , Shelley Michael J.
Published: June 2011

We present a model of cytoplasmically driven microtubule-based pronuclear motion in the single-celled
Caenorhabditis elegans
embryo. In this model, a centrosome pair at the male pronucleus initiates stochastic microtubule (MT) growth. These MTs encounter motor proteins, distributed throughout the cytoplasm, that attach and exert a pulling force. The consequent MT-length-dependent pulling forces drag the pronucleus through the cytoplasm. On physical grounds, we assume that the motor proteins also exert equal and opposite forces on the surrounding viscous cytoplasm, here modeled as an incompressible Newtonian fluid constrained within an ellipsoidal eggshell. This naturally leads to streaming flows along the MTs. Our computational method is based on an immersed boundary formulation that allows for the simultaneous treatment of fluid flow and the dynamics of structures immersed within. Our simulations demonstrate that the balance of MT pulling forces and viscous nuclear drag is sufficient to move the pronucleus, while simultaneously generating minus-end directed flows along MTs that are similar to the observed movement of yolk granules toward the center of asters. Our simulations show pronuclear migration, and moreover, a robust pronuclear centration and rotation very similar to that observed in vivo. We find also that the confinement provided by the eggshell significantly affects the internal dynamics of the cytoplasm, increasing by an order of magnitude the forces necessary to translocate and center the pronucleus.
Four amino acids guide the assembly or disassembly of
Arabidopsis
histone H3.3-containing nucleosomes
Authors: Shi Leilei , Wang Jing , Hong Fang , Spector David L. , Fang Yuda
Published: June 2011

The histone variant H3.3 and the canonical histone H3.1, which differ in only 4- to 5-aa positions, are coexpressed in complex multicellular eukaryotes from fly to human and plant. H3.3 is mainly associated with active chromatin by replacing H3.1 through chaperones such as histone regulator A, death domain associated protein DAXX, thalassemia/mental retardation syndrome X-linked homolog ATRX, or proto-oncogene protein DEK and plays important roles in the germline, epigenetic memory, and reprogramming. However, the signals within H3.3 that serve as a guide for its dynamic deposition or depletion in plant chromatin are not clear. Here, we show that
Arabidopsis
histone H3.3 differs from H3.1 by 4-aa sites: amino acids 31, 41, 87, and 90. Although histone H3.1 is highly enriched in chromocenters, H3.3 is present in nucleolar foci in addition to being diffusely distributed in the nucleoplasm. We have evaluated the function of the 4 aa that differ between H3.1 and H3.3. We show that amino acid residue 87, and to some extent residue 90, of
Arabidopsis
histone H3.3 are critical for its deposition into rDNA arrays. When RNA polymerase I-directed nucleolar transcription is inhibited, wild type H3.3, but not H3.3 containing mutations at residues 31 and 41, is depleted from the rDNA arrays. Together, our results are consistent with a model in which amino acids 87 and 90 in the core domain of H3.3 guide nucleosome assembly, whereas amino acids 31 and 41 in the N-terminal tail of
Arabidopsis
H3.3 guide nucleosome disassembly in nucleolar rDNA.
Metabolomic analysis ofArabidopsisreveals hemiterpenoid glycosides as products of a nitrate ion-regulated, carbon flux overflow
Authors: Ward Jane L. , Baker John M. , Llewellyn Aimee M. , Hawkins Nathaniel D. , Beale Michael H.
Published: June 2011

An understanding of the balance between carbon and nitrogen assimilation in plants is key to future bioengineering for a range of applications. Metabolomic analysis of the model plant,Arabidopsis thaliana, using combined NMR-MS revealed the presence of two hemiterpenoid glycosides that accumulated in leaf tissue, to ~1% dry weight under repeated nitrate-deficient conditions. The formation of these isoprenoids was correlated with leaf nitrate concentrations that could also be assayed in the metabolomic data using a unique flavonoid–nitrate mass spectral adduct. Analysis of leaf and root tissue from plants grown in hydroponics with a variety of root stressors identified the conditions under which the isoprenoid pathway in leaves was diverted to the hemiterpenoids. These compounds were strongly induced by root wounding or oxidative stress and weakly induced by potassium deficiency. Other stresses such as cold, saline, and osmotic stress did not induce the compounds. Replacement of nitrate with ammonia failed to suppress the formation of the hemiterpenoids, indicating that nitrate sensing was a key factor. Feeding of intermediates was used to study aspects of 2-C-methyl-d-erythritol-4-phosphate pathway regulation leading to hemiterpenoid formation. The formation of the hemiterpenoids in leaves was strongly correlated with the induction of the phenylpropanoids scopolin and coniferin in roots of the same plants. These shunts of photosynthetic carbon flow are discussed in terms of overflow mechanisms that have some parallels with isoprene production in tree species.
Instant fabrication and selection of folded structures using drop impact
Authors: Antkowiak Arnaud , Audoly Basile , Josserand Christophe , Neukirch Sébastien , Rivetti Marco
Published: June 2011

A drop impacting a target cutout in a thin polymer film is wrapped by the film in a dynamic sequence involving both capillary forces and inertia. Different 3D structures can be produced from a given target by slightly varying the impact parameters. A simplified model for a nonlinear dynamic Elastica coupled with a drop successfully explains this shape selection and yields detailed quantitative agreement with experiments. This first venture into the largely unexplored dynamics of elastocapillary assemblies opens up the perspective of mass production of 3D packages with individual shape selection.
Reshuffling genomic landscapes to study the regulatory evolution of
Hox
gene clusters
Authors: Tschopp Patrick , Fraudeau Nadine , Béna Frédérique , Duboule Denis
Published: June 2011

The emergence of Vertebrata was accompanied by two rounds of whole-genome duplications. This enabled paralogous genes to acquire novel functions with high evolutionary potential, a process suggested to occur mostly by changes in gene regulation, rather than in protein sequences. In the case of
Hox
gene clusters, such duplications favored the appearance of distinct global regulations. To assess the impact of such “regulatory evolution” upon neo-functionalization, we developed PANTHERE (PAN-genomic Translocation for Heterologous Enhancer RE-shuffling) to bring the entire megabase-scale
HoxD
regulatory landscape in front of the
HoxC
gene cluster via a targeted translocation in vivo. At this chimeric locus,
Hoxc
genes could both interpret this foreign regulation and functionally substitute for their
Hoxd
counterparts. Our results emphasize the importance of evolving regulatory modules rather than their target genes in the process of neo-functionalization and offer a genetic tool to study the complexity of the vertebrate regulatory genome.
Using implementation intentions prompts to enhance influenza vaccination rates
Authors: Milkman Katherine L. , Beshears John , Choi James J. , Laibson David , Madrian Brigitte C.
Published: June 2011

We evaluate the results of a field experiment designed to measure the effect of prompts to form implementation intentions on realized behavioral outcomes. The outcome of interest is influenza vaccination receipt at free on-site clinics offered by a large firm to its employees. All employees eligible for study participation received reminder mailings that listed the times and locations of the relevant vaccination clinics. Mailings to employees randomly assigned to the treatment conditions additionally included a prompt to write down either (
i
) the date the employee planned to be vaccinated or (
ii
) the date and time the employee planned to be vaccinated. Vaccination rates increased when these implementation intentions prompts were included in the mailing. The vaccination rate among control condition employees was 33.1%. Employees who received the prompt to write down just a date had a vaccination rate 1.5 percentage points higher than the control group, a difference that is not statistically significant. Employees who received the more specific prompt to write down both a date and a time had a 4.2 percentage point higher vaccination rate, a difference that is both statistically significant and of meaningful magnitude.
Female extrapair mating behavior can evolve via indirect selection on males
Authors: Forstmeier Wolfgang , Martin Katrin , Bolund Elisabeth , Schielzeth Holger , Kempenaers Bart
Published: June 2011

In many species that form socially monogamous pair bonds, a considerable proportion of the offspring is sired by extrapair males. This observation has remained a puzzle for evolutionary biologists: although mating outside the pair bond can obviously increase the offspring production of males, the benefits of such behavior to females are less clear, yet females are known to actively solicit extrapair copulations. For more than two decades adaptionist explanations have dominated the discussions, yet remain controversial, and genetic constraint arguments have been dismissed without much consideration. An intriguing but still untested hypothesis states that extrapair mating behavior by females may be affected by the same genetic variants (alleles) as extrapair mating behavior by males, such that the female behavior could evolve through indirect selection on the male behavior. Here we show that in the socially monogamous zebra finch, individual differences in extrapair mating behavior have a hereditary component. Intriguingly, this genetic basis is shared between the sexes, as shown by a strong genetic correlation between male and female measurements of extrapair mating behavior. Hence, positive selection on males to sire extrapair young will lead to increased extrapair mating by females as a correlated evolutionary response. This behavior leads to a fundamentally different view of female extrapair mating: it may exist even if females obtain no net benefit from it, simply because the corresponding alleles were positively selected in the male ancestors.
Short- and long-term benefits of cognitive training
Authors: Jaeggi Susanne M. , Buschkuehl Martin , Jonides John , Shah Priti
Published: June 2011

Does cognitive training work? There are numerous commercial training interventions claiming to improve general mental capacity; however, the scientific evidence for such claims is sparse. Nevertheless, there is accumulating evidence that certain cognitive interventions are effective. Here we provide evidence for the effectiveness of cognitive (often called “brain”) training. However, we demonstrate that there are important individual differences that determine training and transfer. We trained elementary and middle school children by means of a videogame-like working memory task. We found that only children who considerably improved on the training task showed a performance increase on untrained fluid intelligence tasks. This improvement was larger than the improvement of a control group who trained on a knowledge-based task that did not engage working memory; further, this differential pattern remained intact even after a 3-mo hiatus from training. We conclude that cognitive training can be effective and long-lasting, but that there are limiting factors that must be considered to evaluate the effects of this training, one of which is individual differences in training performance. We propose that future research should not investigate whether cognitive training works, but rather should determine what training regimens and what training conditions result in the best transfer effects, investigate the underlying neural and cognitive mechanisms, and finally, investigate for whom cognitive training is most useful.
Near-UV cyanobacteriochrome signaling system elicits negative phototaxis in the cyanobacterium
Synechocystis
sp. PCC 6803
Authors: Song Ji-Young , Cho Hye Sun , Cho Jung-Il , Jeon Jong-Seong , Lagarias J. Clark , Park Youn-Il
Published: June 2011

Positive phototaxis systems have been well studied in bacteria; however, the photoreceptor(s) and their downstream signaling components that are responsible for negative phototaxis are poorly understood. Negative phototaxis sensory systems are important for cyanobacteria, oxygenic photosynthetic organisms that must contend with reactive oxygen species generated by an abundance of pigment photosensitizers. The unicellular cyanobacterium
Synechocystis
sp. PCC6803 exhibits type IV pilus-dependent negative phototaxis in response to unidirectional UV-A illumination. Using a reverse genetic approach, together with biochemical, molecular genetic, and RNA expression profiling analyses, we show that the cyanobacteriochrome locus (
slr1212/uirS
) of
Synechocystis
and two adjacent response regulator loci (
slr1213/uirR
and the PatA-type regulator
slr1214/lsiR
) encode a UV-A–activated signaling system that is required for negative phototaxis. We propose that UirS, which is membrane-associated via its
ETR1
domain, functions as a UV-A photosensor directing expression of
lsiR
via release of bound UirR, which targets the
lsiR
promoter. Constitutive expression of LsiR induces negative phototaxis under conditions that normally promote positive phototaxis. Also induced by other stresses, LsiR thus integrates light inputs from multiple photosensors to determine the direction of movement.
Osmotic stress triggers toxin production by the dinoflagellate
Karenia brevis
Authors: Errera Reagan M. , Campbell Lisa
Published: June 2011

With the increase in frequency of harmful algal blooms (HABs) worldwide, a better understanding of the mechanisms that influence toxin production is needed.
Karenia brevis
, the major HAB dinoflagellate in the Gulf of Mexico, produces potent neurotoxins, known as brevetoxins. Human health is directly impacted by blooms of
K. brevis
through consumption of shellfish contaminated by accumulated brevetoxins (neurotoxic shellfish poisoning) or from aerosolized brevetoxins in sea spray (reduced respiratory function); however, the reason for brevetoxin production has remained a mystery. Here we show that brevetoxin production increased dramatically in response to osmotic stress in three of the four
K. brevis
clones examined. By rapidly changing salinity to simulate a shift from oceanic conditions to a decreased salinity typical of coastal conditions, brevetoxin production was triggered. As a result, brevetoxin cell quota increased by >14-fold, while growth rate remained unchanged. Live images of
K. brevis
cells were also examined to assess changes in cell volume. In the
K. brevis
Wilson clone, cells responded quickly to hypoosmotic stress by increasing their brevetoxin cell quota from ∼10 to 160 pg of brevetoxin per cell, while cell volume remained stable. In contrast, the
K. brevis
SP1 clone, which has a consistently low brevetoxin cell quota (<1 pg per cell), was unable to balance the hypoosmotic stress, and although brevetoxin production remained low, average cell volume increased. Our findings close a critical gap in knowledge regarding mechanisms for toxin production in
K. brevis
by providing an explanation for toxin production in this harmful dinoflagellate.
Chemical genetic screen identifies
Toxoplasma
DJ-1 as a regulator of parasite secretion, attachment, and invasion
Authors: Hall Carolyn I. , Reese Michael L. , Weerapana Eranthie , Child Matthew A. , Bowyer Paul W. , Albrow Victoria E. , Haraldsen Jeralyn D. , Phillips MacDonald R. , Sandoval Edgar Deu , Ward Gary E. , Cravatt Benjamin F. , Boothroyd John C. , Bogyo Matthew
Published: June 2011

Toxoplasma gondii
is a member of the phylum Apicomplexa that includes several important human pathogens, such as
Cryptosporidium
and
Plasmodium falciparum
, the causative agent of human malaria. It is an obligate intracellular parasite that can cause severe disease in congenitally infected neonates and immunocompromised individuals. Despite the importance of attachment and invasion to the success of the parasite, little is known about the underlying mechanisms that drive these processes. Here we describe a screen to identify small molecules that block the process of host cell invasion by the
T. gondii
parasite. We identified a small molecule that specifically and irreversibly blocks parasite attachment and subsequent invasion of host cells. Using tandem orthogonal proteolysis–activity-based protein profiling, we determined that this compound covalently modifies a single cysteine residue in a poorly characterized protein homologous to the human protein DJ-1. Mutation of this key cysteine residue in the native gene sequence resulted in parasites that were resistant to inhibition of host cell attachment and invasion by the compound. Further analysis of the invasion phenotype confirmed that modification of Cys127 on TgDJ-1 resulted in a block of microneme secretion and motility, even in the presence of direct stimulators of calcium release. Together, our results suggest that TgDJ-1 plays an important role that is likely downstream of the calcium flux required for microneme secretion, parasite motility, and subsequent invasion of host cells.
Two classes of BRC repeats in BRCA2 promote RAD51 nucleoprotein filament function by distinct mechanisms
Authors: Carreira Aura , Kowalczykowski Stephen C.
Published: June 2011

The human tumor suppressor protein BRCA2 plays a key role in recombinational DNA repair. BRCA2 recruits RAD51 to sites of DNA damage through interaction with eight conserved motifs of approximately 35 amino acids, the BRC repeats; however, the specific function of each repeat remains unclear. Here, we investigated the function of the individual BRC repeats by systematically analyzing their effects on RAD51 activities. Our results reveal the existence of two categories of BRC repeats that display unique functional characteristics. One group, comprising BRC1, -2, -3, and -4, binds to free RAD51 with high affinity. The second group, comprising BRC5, -6, -7, and -8, binds to free RAD51 with low affinity but binds to the RAD51-ssDNA filament with high affinity. Each member of the first group reduces the ATPase activity of RAD51, whereas none of the BRC repeats of the second group affects this activity. Thus, through different mechanisms, both types of BRC repeats bind to and stabilize the RAD51 nucleoprotein filament on ssDNA. In addition, members of the first group limit binding of RAD51 to duplex DNA, where members of the second group do not. Only the first group enhances DNA strand exchange by RAD51. Our results suggest that the two groups of BRC repeats have differentially evolved to ensure efficient formation of a nascent RAD51 filament on ssDNA by promoting its nucleation and growth, respectively. We propose that the BRC repeats cooperate in a partially redundant but reinforcing manner to ensure a high probability of RAD51 filament formation.
Beta oscillations in the monkey sensorimotor network reflect somatosensory decision making
Authors: Haegens Saskia , Nácher Verónica , Hernández Adrián , Luna Rogelio , Jensen Ole , Romo Ranulfo
Published: June 2011

The neuronal correlate of perceptual decision making has been extensively studied in the monkey somatosensory system by using a vibrotactile discrimination task, showing that stimulus encoding, retention, and comparison are widely distributed across cortical areas. However, from a network perspective, it is not known what role oscillations play in this task. We recorded local field potentials (LFPs) from diverse cortical areas of the sensorimotor system while one monkey performed the vibrotactile discrimination task. Exclusively during stimulus presentation, a periodic response reflecting the stimulus frequency was observed in the somatosensory regions, suggesting that after initial processing, the frequency content of the stimulus is coded in some other way than entrainment. Interestingly, we found that oscillatory activity in the beta band reflected the dynamics of decision making in the monkey sensorimotor network. During the comparison and decision period, beta activity showed a categorical response that reflected the decision of the monkey and distinguished correct from incorrect responses. Importantly, this differential activity was absent in a control condition that involved the same stimulation and response but no decision making required, suggesting it does not merely reflect the maintenance of a motor plan. We conclude that beta band oscillations reflect the temporal and spatial dynamics of the accumulation and processing of evidence in the sensorimotor network leading to the decision outcome.
Tumor-initiating stem cells of squamous cell carcinomas and their control by TGF-β and integrin/focal adhesion kinase (FAK) signaling
Authors: Schober Markus , Fuchs Elaine
Published: June 2011

Cancer stem cells (CSCs) sustain tumor growth through their ability to self-renew and to generate differentiated progeny. These functions endow CSCs with the potential to initiate secondary tumors bearing characteristics similar to those of the parent. Recently the hair follicle stem cell marker CD34 was used to purify a CSC-like cell population from early skin tumors arising from treatment with 7,12-dimethylbenz[α]anthracene/12-o-tetradecanoylphorbol-13-acetate, which typically generates benign papillomas that occasionally progress to squamous cell carcinomas (SCCs). In the present study, we identify and characterize CSCs purified from malignant SCCs. We show that SCCs contain two highly tumorigenic CSC populations that differ in CD34 levels but are enriched for integrins and coexist at the SCC–stroma interface. Intriguingly, whether CD34
lo
or CD34
hi
, α6
hi
β1
hi
populations can initiate secondary tumors by serial limit-dilution transplantation assays, but α6
lo
β1
lo
populations cannot. Moreover, secondary tumors generated from a single CSC of either subtype contain both CD34
lo
and CD34
hi
α6
hi
β1
hi
CSCs, indicating their nonhierarchical organization. Genomic profiling and hierarchical cluster analysis show that these two CSC subtypes share a molecular signature distinct from either the CD34
−
epidermal or the CD34
hi
hair follicle stem cell signature. Although closely related, α6
hi
β1
hi
CD34
lo
and α6
hi
β1
hi
CD34
hi
CSCs differ in cell-cycle gene expression and proliferation characteristics. Indeed, proliferation and expansion of α6
hi
β1
hi
CD34
hi
CSCs is sensitive to whether they can initiate a TGF-β receptor II–mediated response to counterbalance elevated focal adhesion kinase-mediated integrin signaling within the tumor. Overall, the coexistence and interconvertibility of CSCs with differing sensitivities to their microenvironment pose challenges and opportunities for SCC cancer therapies.
Technology enhanced learning
Authors: Dror Itiel E.
Published: June 2011

Training (whether traditional, e-learning, or blended learning) is intimately connected with and dependent on the human cognitive system. Learning means that the cognitive system acquires information and stores it for further use. If these processes do not occur properly, then the learners will not initially acquire the information, and even if they do, then they will not be able to recall it later, or/and the information will not be utilised and behaviour will not be modified. Regardless whether the objective is learning new information (e.g., compliance regulations, product specifications, etc.), acquiring new skills (e.g., operating a new apparatus, customer service, time management, etc.), or knowledge sharing and transfer within or across organisations — the processes of acquiring, storing and applying the information are critical. The question is how to achieve these cornerstones of learning and whether technology can enhance them. The answer is clear: The learning must fit human cognition. There is a lot of scientific knowledge and research on human cognition and learning. The difficult and tricky challenge is how to translate this theoretical and academic research into practical ways to utilise technology so as to enhance learning. By bridging basic research about learning and the brain into ways of using learning technologies, one is able to create sophisticated learning programs. These take into account and build on the architecture of cognition, and as a consequence produce effective and efficient technology enhanced learning.
Tautology as presumptive meaning
Authors: Meibauer Jörg
Published: June 2011

Ever since the seminal work of Paul Grice, tautologies such as Business is business have been discussed from a number of angles. While most approaches assume that tautological utterances have to do with the operation of conversational maxims, an integrated analysis is still lacking. This paper makes an attempt at analysing tautologies within the framework of Levinson (2000), who proposes a distinction between three pragmatic levels, namely Indexical Pragmatics, Gricean Pragmatics 1, and Gricean Pragmatics 2. It is shown that observations of Ward and Hirschberg (1991) on the exclusion of alternatives, the claim of Autenrieth (1997) that the second NP in nominal equatives is predicative, and the recent insights of Bulhof and Gimbel (2004) on ‘deep’ tautology, may be fruitfully integrated within Levinson’s framework. The gist of this paper is to show that tautologies are not as tautological as once thought, because implicatures influence their truth conditions. Data are drawn from the author’s corpus of authentic German examples.
The structure of misunderstandings
Authors: Schlesinger Izchak M. , Hurvitz Sharon
Published: June 2011

In this paper we introduce a detailed and multi-faceted characterization of misunderstandings. The proposal attempts to capture the structure of misunderstandings in terms of several constructs: the message as intended by the speaker, the message as construed by the hearer, and the message as understood by an ‘objective’ judge. In addition, we suggest that the message the speaker intends the hearer to retrieve and the hearer’s perception of the speaker’s intentions should also be taken into account. Misunderstandings can also be classified according to the phase of the comprehension process at which they occur (the perception of the speaker’s message, its linguistic processing, discovering the implicatures, and so on).
The experiential basis of speech and writing as different cognitive domains
Authors: Kravchenko Alexander V.
Published: June 2011

Traditionally, writing is viewed as a code that stands in one-to-one correspondence to spoken language, which is therefore also viewed as a code. However, this is a delusion, which is shared by educators and has serious consequences for cognition, both on individual and on social levels. Natural linguistic signs characteristic for the activity of languaging and their symbolizations (graphic markings) are ontologically different phenomena; speech and writing belong to experiential domains of different dynamics. These dynamics impact differently on the linguistic/behavioral strategies of individuals and communities, viewed as second- and third-order living systems operating in a consensual domain as structure-determined systems. Failure to acknowledge this contributes to the spread of functional illiteracy in modern societies, which may lead to cognitive/communicative dysfunction. Technology-enhanced new literacies challenge the value of traditional written culture, raising questions about the relationship between speech and writing and their roles in human evolution
Languaging in Shakespeare’s theatre
Authors: Tribble Evelyn
Published: June 2011

The enshrinement of William Shakespeare’s plays in printed editions has led to the assumption that they were performed with an ideal of exact verbatim reproduction of the language. Evidence drawn from alternative versions of the plays circulating in Shakespeare’s lifetime and from our knowledge of the material practices of playing in early modern England presents us with a very different picture. Performing practices in this period were marked by a tension between improvisational here-and-now languaging practices, including the use of gesture in playing, and a new set of expectations based upon an emergent conception of plays as written documents.