bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Internet, Everyone Knows You're a Dog.A Review Essay
Authors: Gershon Ilana
Published: October 2011

Ethnographers of new media face a challenge nowadays because they write about technologies people love to discuss and about which journalists love to write. They often find themselves writing against myths about digital media users that other digital media scholars, journalists, and even people interviewed hold in common. In the first decade of Internet research, skeptical scholars often wrote against assumptions about how social practices in virtual spaces differed from offline practices (see Dibbell 1998; Turkle 1995; Stone 1996). They were critiquing many of the premises that accompany an understanding of the virtual as “spaces or placesapart fromthe rest of social life” (Miller, Slater, and Suchman 2004: 77) in which people were supposedly experimenting with new forms of sociality and identity. While these debates continue to haunt more recent ethnographies of virtual worlds (see Boellstorff 2008; Nardi 2010; Taylor 2006), critical scholars of new media are now also addressing commonly held assumptions about the Internet when its use is explicitly understoodnotto be part of a sociality distinct from offline life. Indeed, the Internet now is taken to be a collection of interfaces for gathering information and conversing with other people—web-based communication can be as integrated into daily life as a phone call or reading a book (for an ethnographic study, see Gershon 2010). This transition from taking the Internet to be virtual to seeing the Internet as a collection of channels of communication has brought with it a new set of widespread presuppositions that ethnography is particularly adept at critiquing.
Stopping of ions in a plasma irradiated by an intense laser field
Authors: Nersisyan H.B. , Deutsch C.
Published: October 2011

The inelastic interaction between heavy ions and an electron plasma in the presence of an intense radiation field (RF) is investigated. The stopping power of the test ion averaged with a period of the RF has been calculated assuming that ω0 > ωp, where ω0 is the frequency of the RF and ωp is the plasma frequency. In order to highlight the effect of the radiation field we present a comparison of our analytical and numerical results obtained for nonzero RF with those for vanishing RF. It has been shown that the RF may strongly reduce the mean energy loss for slow ions while increasing it at high–velocities. Moreover, it has been shown, that acceleration of the projectile ion due to the RF is expected at high–velocities and in the high–intensity limit of the RF, when the quiver velocity of the plasma electrons exceeds the ion velocity.
Just Because You're Paranoid Doesn't Mean They Aren't Out to Get You: Rejoinder to Bensel
Authors: DeCanio Samuel
Published: October 2011

Richard Bensel's comment on my article “Populism, Paranoia, and the Politics of Free Silver” is, like all of his writing, thoughtful, careful, detailed, and well written. However, I find that I disagree with a number of Bensel's points. In this response I try to clarify areas of disagreement and point to several cases where I believe my argument has been slightly misconstrued, which is understandable given the length and complexity of the paper.
The meaning of the English present participle
Authors: DE SMET HENDRIK , HEYVAERT LIESBET
Published: October 2011

While earlier descriptions of the English present participle have tended to be too general or too exclusively focused on its progressive meaning, this article aims to present an account of the meanings of the English present participle that captures their full richness. It starts from the observation that many (though not all) present participle clauses/phrases are paradigmatically related to adjectival phrases, as manifested in their distributional properties (e.g. a challenging year, those living alone). The article analyses the semantic effects that arise from the tension between the verbal semantics of the participial stem and the adjectival semantics of the syntactic slot. These effects involve accommodation of the verbal situation to the requirement that a situation is represented as time-stable and as simultaneous to some contextually given reference time. The progressive meaning is one such semantic effect, but participles may also assume iterative, habitual or gnomic readings. Some construction-specific semantic extensions of this adjectival template are identified and a tentative explanation is offered for them. Those constructions where the present participle has lost its semantic association with adjective phrases, such as the progressive construction and integrated participle clauses, are shown to display loosening or specialization of semantic constraints.
Diet quality, physical activity, body weight and health-related quality of life among grade 5 students in Canada
Authors: Wu Xiu Yun , Ohinmaa Arto , Veugelers Paul J
Published: October 2011

Objective

To assess how diet quality, physical activity and body weight are related to health-related quality of life (HRQOL) among children in the Canadian province of Alberta.

Design

In 2008, we surveyed 3421 grade 5 students and their parents from 148 randomly selected schools. Students completed the Harvard Food Frequency Questionnaire, questions on physical activities, and had their height and weight measured. The HRQOL of the students was assessed using the EQ-5D-Y. Parents completed questions on socio-economic background and children's lifestyle. We applied multilevel regression methods to examine the importance of children's diet quality, physical activity and weight status for the EQ-5D-Y Visual Analogue Scale and for the EQ-5D-Y dimensions.

Setting

The province of Alberta, Canada.

Subjects

Grade 5 students.

Results

Students with better diet quality, higher physical activity levels and normal body weights were statistically significantly more likely to report better HRQOL than students who ate less healthily, were less active or were overweight or obese.

Conclusions

The importance of diet quality, physical activity and body weight status for HRQOL may help justify broader implementation of school health programmes that promote healthy eating and active living, as these programmes will help reduce the burden of childhood obesity and improve quality of life.
Sea surface temperature variability in the subpolar Atlantic over the last two millennia
Authors: Sicre M.‐A. , Hall I. R. , Mignot J. , Khodri M. , Ezat U. , Truong M.‐X. , Eiríksson J. , Knudsen K.‐L.
Published: October 2011

A decadal resolution time series of sea surface temperature (SST) spanning the last two millennia is reconstructed by combining a proxy record from a new sediment sequence with previously published data from core MD99–2275, north of Iceland. The alkenone based SST reconstruction is validated with historic observational data and compared to a new similar temporal resolution reconstruction obtained from sediment core RAPiD21–3K, in the subpolar North Atlantic. The two SST paleorecords show consistent multidecadal scale coolings throughout the interval and similar expressions during the contrasted climatic periods ‘colloquially known’ as the Medieval Climatic Anomaly (MCA) and Little Ice Age (LIA). In order to further understand the temporal and spatial SST variations and investigate the influence of natural forcings on the observed SST changes during the last millennium, we compare our time series to simulations using the Institut Pierre‐Simon Laplace IPSLCM4‐v2 climate model. This comparison highlights the potential importance of volcanism as a natural forcing driving coherent abrupt cooling events captured in the subpolar North Atlantic records.
Biophysical Mechanisms Supporting Conscious Perception: Prospects for an Artificial Astrocyte
Authors: Pereira Alfredo
Published: October 2011

In perceptual processes, signals carrying information about a stimulus are transmitted through multiple processing lines to populations of receptive neurons and thalamocortical circuits, leading to the formation of a spatial ensemble of local field potentials. This paper addresses the problem of how the brain integrates patterns embodied in local fields to (re)construct the stimulus in a conscious episode. Four examples of human perception are given to illustrate the requirements of the integrative process. Considering the strategic position of astrocytes, mediating somatic signals carried by blood flow and information carried by the neuronal network, as well as their intrinsic information processing capabilities, these cells are in an adequate condition to integrate spatially distributed information. The amplitude-modulated calcium waveform in astrocytes is a multiscale phenomenon, simultaneously operating on temporal scales of milliseconds and seconds, as well as in micro and macro spatial scales. Oscillatory synchrony, constructive wave interference and communication by means of ionic antennas are proposed to constitute a neuro-astroglial self-organizing mechanism of perceptual integration and feeling of the integrated information content. A pilot experiment of a single artificial astrocyte is suggested, both as a test for the hypothesis of astroglial information integration and a multimedia technological application of the model.
New insights into the polyploid complex Cenchrus ciliaris L. (Poaceae) show its capacity for gene flow and recombination processes despite its apomictic nature
Authors: Kharrat-Souissi Amina , Baumel Alex , Torre Franck , Juin Marianick , Siljak-Yakovlev Sonja , Roig Anne , Chaieb Mohamed
Published: October 2011

Cenchrus ciliaris L. is a C4 perennial grass of arid lands which is under the focus of different ecological issues such as response to desertification, quality of forage grass and impacts of invasions. Here, molecular and morphological analyses of the genetic diversity of several Tunisian provenances of C. ciliaris were performed to better understand the phenotypic polymorphism of this agamospermous and polyploid grass. Ten phenotypic traits associated with productivity were measured in a common garden environment. Amplified Fragment Length Polymorphism (AFLP) markers were developed to investigate the structure of genetic diversity among and within provenances and between the three ploidy levels. Heritable phenotypic traits showed considerable differences within provenances. Surprisingly, AFLP markers revealed the existence of genotypic variations between individuals of the same sibship and a high G/N value (0.55). A neighbour-joining tree based on AFLP markers revealed three major groups; tetraploid, pentaploid and a mix of pentaploid and hexaploids. These groups do not correspond completely to the geographical origin of samples. The results underline the possibility of sexual reproduction, recombination and gene flow within and between populations of C. ciliaris. In respect with the well known dynamic nature of polyploid genomes, these results should have strong consequences for the future management of this grass for both conservation and invasion issues.
Protein content and electrophoretic profile of insect galls on susceptible and resistant host plants of Bauhinia brevipes Vogel (Fabaceae)
Authors: Detoni Michelle de Lima , Vasconcelos Eveline Gomes , Maia Ana Carolina Ribeiro Gomes , Gusmão Michélia Antônia do Nascimento , Isaias Rosy Mary dos Santos , Soares Geraldo Luiz Gonçalves , Santos Jean Carlos , Fernandes G. Wilson
Published: October 2011

Gall induction, mediated by insect-herbivore chemical stimuli, is the result from anatomical and biochemical alterations in the host-plant tissues that provides shelter, food and defence against natural enemies and the harsh environment to the gall inducer. Schizomya macrocapillata Maia (Diptera, Cecidomyiidae) induces galls on Bauhinia brevipes Vogel (Fabaceae); the galls are spherical, with long reddish hairs that cover the adaxial wall surface of the gall, and a protuberance is observed on the abaxial leaf surface. Some plants are resistant to gall formation and, in many cases, this formation is inhibited by hypersensitive reaction. In the present work, samples from different parts of the non-galled and galled tissues from resistant and susceptible plants were carefully dissected. Indicating elevated metabolic activity, the protein concentration was 1.5–4.5-fold higher in the abaxial portion of the galls than in any other tissues, regardless of whether the galls were from resistant or susceptible plants. Different tissues from susceptible and resistant plants had distinct protein concentrations, and the fractionation of the proteins by SDS–PAGE and silver-staining showed shared and/or specific polypeptides. We hypothesise that specific proteins, possibly from distinct metabolic pathways, are involved in the physiological processes that determine whether the plant shows total and/or partial host resistance to the galling-insect attack.
Steady-state DGT fluxes of nanoparticulate metal complexes
Authors: van Leeuwen Herman P.
Published: October 2011

Environmental contextDiffusive gel layer techniques can measure fluxes of chemical species in aqueous environmental media. Nanoparticulate metal complexes are small enough to penetrate gels, but their diffusive response is much slower than that of the free metal ions. Hence, time-resolved analysis of the diffusive flux of the complex sample is proposed as a chemical speciation tool for the nanodomain.
AbstractFor a fully labile complex system, the diffusive gradients in thin film (DGT) metal flux approaches the fairly simple limit defined by the joint diffusion of the free metal ion and the complex species in the gel layer. Natural soft nanoparticulate complexes, such as those with humics and fulvics, generally enter the DGT gel phase and some of them may even be adsorbed by the gel matrix. The time characteristics of the DGT response are affected by a lower rate of diffusion, as well as by possible accumulation of nanoparticulate species in the gel layer. Several cases are discussed in some detail on the basis of numerical analysis of the diffusion process. If the difference between the diffusion coefficients of the free metal ion and the nanoparticulate complex is sufficiently large, the time-resolved DGT flux allows for distinction between these two types of species.
How well can we predict and measure metal speciation in freshwaters?
Authors: Hamilton-Taylor John , Ahmed Imad A. M. , Davison William , Zhang Hao
Published: October 2011

Environmental contextThe ‘speciation’ of metals is concerned with their different chemical and physical forms, a detailed knowledge of which is essential to understand what happens to metals in lakes and rivers, and their effects on living organisms. There have been many advances in recent years in our ability both to measure and predict metal speciation in natural waters, but it is not clear just how accurately these can be applied under field conditions. The current state of play is assessed to provide a better understanding of the related uncertainties, and suggestions are made for ways to reduce these uncertainties and possibly improve our predictive capabilities.
Inherent nitrogen deficiency in Pistacia lentiscus preferentially affects photosystem I: a seasonal field study
Authors: Nikiforou Constantinos , Manetas Yiannis
Published: October 2011

Although it is widely documented that CO2 assimilation rates are positively correlated with leaf nitrogen, corresponding studies on a link between this nutrient and photosynthetic light reactions are scarce, especially under natural field conditions. In this investigation, we exploited natural variation in the nitrogen content of mature leaves of Pistacia lentiscus L. (mastic tree) in conjunction with fast chlorophyll a fluorescence rise (the OJIP curves) analysed according to the ‘JIP test’, as this was recently modified to allow for the assessment of events in or around PSI. The results depended on the sampling season, with low nitrogen leaves displaying lower efficiencies for electron flow from intermediate carriers to final PSI acceptors, and lower relative pool sizes of these acceptors, both during the autumn and winter. However, parameters related to the PSII) activity (i.e. quantum yields for photon trapping and electron flow along PSII and the efficiency of a trapped exciton to move an electron from the first plastoquoinone electron acceptor of PSII to intermediate carriers) were limited by low nitrogen only during the winter period. As a result, parameters like the quantum yield of total electron flow along both photosystems as well as the total photosynthetic performance index (PItotal) were positively correlated with leaf nitrogen independently of the season. We conclude that nitrogen deficiency under field conditions preferentially affects PSI activity while the effects on PSII are evident only during the stressful period of the year.
Critical roles of chemokine receptor CCR10 in regulating memory IgA responses in intestines
Authors: Hu Shaomin , Yang KangKang , Yang Jie , Li Ming , Xiong Na
Published: October 2011

Chemokine receptor CCR10 is expressed by all intestinal IgA-producing plasma cells and is suggested to play an important role in positioning these cells in the lamina propria for proper IgA production to maintain intestinal homeostasis and protect against infection. However, interfering with CCR10 or its ligand did not impair intestinal IgA production under homeostatic conditions or during infection, and the in vivo function of CCR10 in the intestinal IgA response remains unknown. We found that an enhanced generation of IgA+cells in isolated lymphoid follicles of intestines offset defective intestinal migration of IgA+cells in CCR10-KO mice, resulting in the apparently normal IgA production under homeostatic conditions and in primary response to pathogen infection. However, the compensatorily generated IgA+cells in CCR10-KO mice carried fewer hypermutations in their Ig heavy chain alleles than those of WT mice, indicating that their IgA repertoires are qualitatively different, which might impact the intestinal homeostasis of microflora. In addition, CCR10-deficient long-lived IgA-producing plasma cells and IgA+memory B cells generated against the pathogen infection could not be maintained properly in intestines. Consequently, IgA memory responses to the pathogen reinfection were severely impaired in CCR10-KO mice. These findings elucidate critical roles of CCR10 in regulating the intestinal IgA response and memory maintenance and could help in design of vaccines against intestinal and possibly other mucosal pathogens.
The telomeric Cdc13 protein interacts directly with the telomerase subunit Est1 to bring it to telomeric DNA ends in vitro
Authors: Wu Yun , Zakian Virginia A.
Published: October 2011

In
Saccharomyces cerevisiae
, a Cdc13–Est1 interaction is proposed to mediate recruitment of telomerase to DNA ends. Here we provide unique in vitro evidence for this model by demonstrating a direct interaction between purified Cdc13 and Est1. The Cdc13–Est1 interaction is specific and requires the in vivo defined Cdc13 recruitment domain. Moreover, in the absence of this interaction, Est1 is excluded from telomeric single-stranded (ss)DNA. The apparent association constand (K
d
) between Est1 and a Cdc13-telomeric ssDNA complex was ∼250 nM. In G2 phase cells, where telomerase is active, Cdc13 and Est1 were sufficiently abundant (∼420 and ∼110 copies per cell, respectively) to support complex formation. Interaction between Cdc13 and Est1 was unchanged by three telomerase-deficient mutations, Cdc13
E252K
(
cdc13-2
), Est1
K444E
(
est1-60
), and Cdc13
S249,255D
, indicating that their telomerase null phenotypes are not due to loss of the Cdc13–Est1 interaction. These data recapitulate in vitro the first step in telomerase recruitment to telomeric ssDNA and suggest that this step is necessary to recruit telomerase to DNA ends.
Tumor suppressor down-regulated in renal cell carcinoma 1 (DRR1) is a stress-induced actin bundling factor that modulates synaptic efficacy and cognition
Authors: Schmidt Mathias V. , Schülke Jan-Philip , Liebl Claudia , Stiess Michael , Avrabos Charilaos , Bock Jörg , Wochnik Gabriela M. , Davies Heather A. , Zimmermann Nicole , Scharf Sebastian H. , Trümbach Dietrich , Wurst Wolfgang , Zieglgänsberger Walter , Turck Christoph , Holsboer Florian , Stewart Michael G. , Bradke Frank , Eder Matthias , Müller Marianne B. , Rein Theo
Published: October 2011

Stress has been identified as a major causal factor for many mental disorders. However, our knowledge about the chain of molecular and cellular events translating stress experience into altered behavior is still rather scant. Here, we have characterized a murine ortholog of the putative tumor suppressor gene
DRR1
as a unique stress-induced protein in brain. It binds to actin, promotes bundling and stabilization of actin filaments, and impacts on actin-dependent neurite outgrowth. Endogenous DRR1 localizes to some, but not all, synapses, with preference for the presynaptic region. Hippocampal virus-mediated enhancement of DRR1 expression reduced spine density, diminished the probability of synaptic glutamate release, and altered cognitive performance. DRR1 emerges as a protein to link stress with actin dynamics, which in addition is able to act on synaptic function and cognition.
Multimodal neuroimaging dissociates hemodynamic and electrophysiological correlates of error processing
Authors: Agam Yigal , Hämäläinen Matti S. , Lee Adrian K. C. , Dyckman Kara A. , Friedman Jesse S. , Isom Marlisa , Makris Nikos , Manoach Dara S.
Published: October 2011

Recognizing errors and adjusting responses are fundamental to adaptive behavior. The error-related negativity (ERN) and error-related functional MRI (fMRI) activation of the dorsal anterior cingulate cortex (dACC) index these processes and are thought to reflect the same neural mechanism. In the present study, we evaluated this hypothesis. Although errors elicited robust dACC activation using fMRI, combined electroencephalography and magnetoencephalography data localized the ERN to the posterior cingulate cortex (PCC). ERN amplitude correlated with fMRI activation in both the PCC and dACC, and these two regions showed coordinated activity based on functional connectivity MRI. Finally, increased microstructural integrity of the posterior cingulum bundle, as measured by diffusion tensor imaging, predicted faster error correction. These findings suggest that the PCC generates the ERN and communicates with the dACC to subserve error processing. They challenge current models that view fMRI activation of the dACC as the hemodynamic reflection of the ERN.
Evidence for evolution in response to natural selection in a contemporary human population
Authors: Milot Emmanuel , Mayer Francine M. , Nussey Daniel H. , Boisvert Mireille , Pelletier Fanie , Réale Denis
Published: October 2011

It is often claimed that modern humans have stopped evolving because cultural and technological advancements have annihilated natural selection. In contrast, recent studies show that selection can be strong in contemporary populations. However, detecting a response to selection is particularly challenging; previous evidence from wild animals has been criticized for both applying anticonservative statistical tests and failing to consider random genetic drift. Here we study life-history variation in an insular preindustrial French-Canadian population and apply a recently proposed conservative approach to testing microevolutionary responses to selection. As reported for other such societies, natural selection favored an earlier age at first reproduction (AFR) among women. AFR was also highly heritable and genetically correlated to fitness, predicting a microevolutionary change toward earlier reproduction. In agreement with this prediction, AFR declined from about 26–22 y over a 140-y period. Crucially, we uncovered a substantial change in the breeding values for this trait, indicating that the change in AFR largely occurred at the genetic level. Moreover, the genetic trend was higher than expected under the effect of random genetic drift alone. Our results show that microevolution can be detectable over relatively few generations in humans and underscore the need for studies of human demography and reproductive ecology to consider the role of evolutionary processes.
Lymphomas that recur after MYC suppression continue to exhibit oncogene addiction
Authors: Choi Peter S. , van Riggelen Jan , Gentles Andrew J. , Bachireddy Pavan , Rakhra Kavya , Adam Stacey J. , Plevritis Sylvia K. , Felsher Dean W.
Published: October 2011

The suppression of oncogenic levels of MYC is sufficient to induce sustained tumor regression associated with proliferative arrest, differentiation, cellular senescence, and/or apoptosis, a phenomenon known as oncogene addiction. However, after prolonged inactivation of MYC in a conditional transgenic mouse model of Eμ-tTA/tetO-MYC T-cell acute lymphoblastic leukemia, some of the tumors recur, recapitulating what is frequently observed in human tumors in response to targeted therapies. Here we report that these recurring lymphomas express either transgenic or endogenous Myc, albeit in many cases at levels below those in the original tumor, suggesting that tumors continue to be addicted to MYC. Many of the recurring lymphomas (76%) harbored mutations in the tetracycline transactivator, resulting in expression of the MYC transgene even in the presence of doxycycline. Some of the remaining recurring tumors expressed high levels of endogenous Myc, which was associated with a genomic rearrangement of the endogenous Myc locus or activation of Notch1. By gene expression profiling, we confirmed that the primary and recurring tumors have highly similar transcriptomes. Importantly, shRNA-mediated suppression of the high levels of MYC in recurring tumors elicited both suppression of proliferation and increased apoptosis, confirming that these tumors remain oncogene addicted. These results suggest that tumors induced by MYC remain addicted to overexpression of this oncogene.
Evidence for short-range helical order in the 30-nm chromatin fibers of erythrocyte nuclei
Authors: Scheffer Margot P. , Eltsov Mikhail , Frangakis Achilleas S.
Published: October 2011

Chromatin folding in eukaryotes fits the genome into the limited volume of the cell nucleus. Formation of higher-order chromatin structures attenuates DNA accessibility, thus contributing to the control of essential genome functions such as transcription, DNA replication, and repair. The 30-nm fiber is thought to be the first hierarchical level of chromatin folding, but the nucleosome arrangement in the compact 30-nm fiber was previously unknown. We used cryoelectron tomography of vitreous sections to determine the structure of the compact, native 30-nm fiber of avian erythrocyte nuclei. The predominant geometry of the 30-nm fiber revealed by subtomogram averaging is a left-handed two-start helix with approximately 6.5 nucleosomes per 11 nm, in which the nucleosomes are juxtaposed face-to-face but are shifted off their superhelical axes with an axial translation of approximately 3.4 nm and an azimuthal rotation of approximately 54°. The nucleosomes produce a checkerboard pattern when observed in the direction perpendicular to the fiber axis but are not interdigitated. The nucleosome packing within the fibers shows larger center-to-center internucleosomal distances than previously anticipated, thus excluding the possibility of core-to-core interactions, explaining how transcription and regulation factors can access nucleosomes.
Carbonates in the Martian meteorite Allan Hills 84001 formed at 18 ± 4 °C in a near-surface aqueous environment
Authors: Halevy Itay , Fischer Woodward W. , Eiler John M.
Published: October 2011

Despite evidence for liquid water at the surface of Mars during the Noachian epoch, the temperature of early aqueous environments has been impossible to establish, raising questions of whether the surface of Mars was ever warmer than today. We address this problem by determining the precipitation temperature of secondary carbonate minerals preserved in the oldest known sample of Mars’ crust—the approximately 4.1 billion-year-old meteorite Allan Hills 84001 (ALH84001). The formation environment of these carbonates, which are constrained to be slightly younger than the crystallization age of the rock (i.e., 3.9 to 4.0 billion years), has been poorly understood, hindering insight into the hydrologic and carbon cycles of earliest Mars. Using “clumped” isotope thermometry we find that the carbonates in ALH84001 precipitated at a temperature of approximately 18 °C, with water and carbon dioxide derived from the ancient Martian atmosphere. Furthermore, covarying carbonate carbon and oxygen isotope ratios are constrained to have formed at constant, low temperatures, pointing to deposition from a gradually evaporating, subsurface water body—likely a shallow aquifer (meters to tens of meters below the surface). Despite the mild temperatures, the apparently ephemeral nature of water in this environment leaves open the question of its habitability.
Dysbindin-1 mutant mice implicate reduced fast-phasic inhibition as a final common disease mechanism in schizophrenia
Authors: Carlson Gregory C. , Talbot Konrad , Halene Tobias B. , Gandal Michael J. , Kazi Hala A. , Schlosser Laura , Phung Quan H. , Gur Raquel E. , Arnold Steven E. , Siegel Steven J.
Published: October 2011

DTNBP1 (dystrobrevin binding protein 1) is a leading candidate susceptibility gene in schizophrenia and is associated with working memory capacity in normal subjects. In schizophrenia, the encoded protein dystrobrevin-binding protein 1 (dysbindin-1) is often reduced in excitatory cortical limbic synapses. We found that reduced dysbindin-1 in mice yielded deficits in auditory-evoked response adaptation, prepulse inhibition of startle, and evoked γ-activity, similar to patterns in schizophrenia. In contrast to the role of dysbindin-1 in glutamatergic transmission, γ-band abnormalities in schizophrenia are most often attributed to disrupted inhibition and reductions in parvalbumin-positive interneuron (PV cell) activity. To determine the mechanism underlying electrophysiological deficits related to reduced dysbindin-1 and the potential role of PV cells, we examined PV cell immunoreactivity and measured changes in net circuit activity using voltage-sensitive dye imaging. The dominant circuit impact of reduced dysbindin-1 was impaired inhibition, and PV cell immunoreactivity was reduced. Thus, this model provides a link between a validated candidate gene and an auditory endophenotypes. Furthermore, these data implicate reduced fast-phasic inhibition as a common underlying mechanism of schizophrenia-associated intermediate phenotypes.
Antibiotic acyldepsipeptides activate ClpP peptidase to degrade the cell division protein FtsZ
Authors: Sass Peter , Josten Michaele , Famulla Kirsten , Schiffer Guido , Sahl Hans-Georg , Hamoen Leendert , Brötz-Oesterhelt Heike
Published: October 2011

The worldwide spread of antibiotic-resistant bacteria has lent urgency to the search for antibiotics with new modes of action that are devoid of preexisting cross-resistances. We previously described a unique class of acyldepsipeptides (ADEPs) that exerts prominent antibacterial activity against Gram-positive pathogens including streptococci, enterococci, as well as multidrug-resistant
Staphylococcus aureus
. Here, we report that ADEP prevents cell division in Gram-positive bacteria and induces strong filamentation of rod-shaped
Bacillus subtilis
and swelling of coccoid
S. aureus
and
Streptococcus pneumoniae
. It emerged that ADEP treatment inhibits septum formation at the stage of Z-ring assembly, and that central cell division proteins delocalize from midcell positions. Using in vivo and in vitro studies, we show that the inhibition of Z-ring formation is a consequence of the proteolytic degradation of the essential cell division protein FtsZ. ADEP switches the bacterial ClpP peptidase from a regulated to an uncontrolled protease, and it turned out that FtsZ is particularly prone to degradation by the ADEP–ClpP complex. By preventing cell division, ADEP inhibits a vital cellular process of bacteria that is not targeted by any therapeutically applied antibiotic so far. Their unique multifaceted mechanism of action and antibacterial potency makes them promising lead structures for future antibiotic development.
Modulation of canonical Wnt signaling by the extracellular matrix component biglycan
Authors: Berendsen Agnes D. , Fisher Larry W. , Kilts Tina M. , Owens Rick T. , Robey Pamela G. , Gutkind J. Silvio , Young Marian F.
Published: October 2011

Although extracellular control of canonical Wnt signaling is crucial for tissue homeostasis, the role of the extracellular microenvironment in modulating this signaling pathway is largely unknown. In the present study, we show that a member of the small leucine-rich proteoglycan family, biglycan, enhances canonical Wnt signaling by mediating Wnt function via its core protein. Immunoprecipitation analysis revealed that biglycan interacts with both the canonical Wnt ligand Wnt3a and the Wnt coreceptor low-density lipoprotein receptor-related protein 6 (LRP6), possibly via the formation of a trimeric complex. Biglycan-deficient cells treated with exogenous Wnt3a had less Wnt3a retained in cell layers compared with WT cells. Furthermore, the Wnt-induced levels of LRP6 phosphorylation and expression of several Wnt target genes were blunted in biglycan-deficient cells. Both recombinant biglycan proteoglycan and biglycan core protein increased Wnt-induced β-catenin/T cell-specific factor–mediated transcriptional activity, and this activity was completely inhibited by Dickkopf 1. Interestingly, recombinant biglycan was able to rescue impaired Wnt signaling caused by a previously described missense mutation in the extracellular domain of human LRP6 (R611C). Furthermore, biglycan's modulation of canonical Wnt signaling affected the functional activities of osteoprogenitor cells, including the RUNX2-mediated transcriptional activity and calcium deposition. Use of a transplant system and a fracture healing model revealed that expression of Wnt-induced secreted protein 1 was decreased in bone formed by biglycan-deficient cells, further suggesting reduced Wnt signaling in vivo. We propose that biglycan may serve as a reservoir for Wnt in the pericellular space and modulate Wnt availability for activation of the canonical Wnt pathway.
Antimicrobial resistance to ceftazidime involving loss of penicillin-binding protein 3 in
Burkholderia pseudomallei
Authors: Chantratita Narisara , Rholl Drew A. , Sim Bernice , Wuthiekanun Vanaporn , Limmathurotsakul Direk , Amornchai Premjit , Thanwisai Aunchalee , Chua Hui Hoon , Ooi Wen Fong , Holden Matthew T. G. , Day Nicholas P. , Tan Patrick , Schweizer Herbert P. , Peacock Sharon J.
Published: October 2011

Known mechanisms of resistance to β-lactam antibiotics include β-lactamase expression, altered drug target, decreased bacterial permeability, and increased drug efflux. Here, we describe a unique mechanism of β-lactam resistance in the biothreat organism
Burkholderia pseudomallei
(the cause of melioidosis), associated with treatment failure during prolonged ceftazidime therapy of natural infection. Detailed comparisons of the initial ceftazidime-susceptible infecting isolate and subsequent ceftazidime-resistant variants from six patients led us to identify a common, large-scale genomic loss involving a minimum of 49 genes in all six resistant strains. Mutational analysis of wild-type
B. pseudomallei
demonstrated that ceftazidime resistance was due to deletion of a gene encoding a penicillin-binding protein 3 (BPSS1219) present within the region of genomic loss. The clinical ceftazidime-resistant variants failed to grow using commonly used laboratory culture media, including commercial blood cultures, rendering the variants almost undetectable in the diagnostic laboratory. Melioidosis is notoriously difficult to cure and clinical treatment failure is common in patients treated with ceftazidime, the drug of first choice across most of Southeast Asia where the majority of cases are reported. The mechanism described here represents an explanation for ceftazidime treatment failure, and may be a frequent but undetected resistance event.
Microtubule-associated protein 1 light chain 3 alpha (LC3)-associated phagocytosis is required for the efficient clearance of dead cells
Authors: Martinez Jennifer , Almendinger Johann , Oberst Andrew , Ness Rachel , Dillon Christopher P. , Fitzgerald Patrick , Hengartner Michael O. , Green Douglas R.
Published: October 2011

The recognition and clearance of dead cells is a process that must occur efficiently to prevent an autoimmune or inflammatory response. Recently, a process was identified wherein the autophagy machinery is recruited to pathogen-containing phagosomes, termed MAPLC3A (LC3)-associated phagocytosis (LAP), which results in optimal degradation of the phagocytosed cargo. Here, we describe the engagement of LAP upon uptake of apoptotic, necrotic, and RIPK3-dependent necrotic cells by macrophages. This process is dependent on some members of the classical autophagy pathway, including Beclin1, ATG5, and ATG7. In contrast, ULK1, despite being required for autophagy, is dispensable for LAP induced by uptake of microbes or dead cells. LAP is required for efficient degradation of the engulfed corpse, and in the absence of LAP, engulfment of dead cells results in increased production of proinflammatory cytokines and decreased production of anti-inflammatory cytokines. LAP is triggered by engagement of the TIM4 receptor by either phosphatidylserine (PtdSer)-displaying dead cells or PtdSer-containing liposomes. Therefore, the consequence of phagocytosis of dead cells is strongly affected by those components of the autophagy pathway involved in LAP.
Taking money and making ideas, or taking ideas and making money
Authors: Vickery Graham
Published: October 2011

Until very recently, Graham Vickery worked for the Organisation for Economic Cooperation and Development in Paris as Principal Administrator of the Information, Computer and Communications Policy Division. He has long been interested in the innovation policies of the member countries, and has been instrumental in shaping many of them.
Managing academic freedom: recent cross-Atlantic developments
Authors: Elliott J.E.
Published: October 2011

This paper charts the legal and institutional status of academic freedom in America after Garcetti v. Ceballos, a key First Amendment case decided by the US Supreme Court in 2006. It also addresses, in comparative compass, academic speech protection in the UK and the EU more broadly. Although a managerial ethos of university governance has reshaped academic freedom on both sides of the Atlantic, the shaping process has not been uniform. Differences in policy formation and institutional structure have produced significant variations in the safeguarding of faculty speech. Policy groups on the Continent have been particularly active in drafting aspirational statements on academic freedom. Both the UK and the EU also have legislation outlining the rights and responsibilities of university teaching and research. No such legislation exists in the US, where the courts have played a central role in determining the legal status of academic speech. Statutory provisions in Europe, by contrast, remain judicially untested. It is anticipated that academic freedom on both sides of the Atlantic will increasingly be defined in contract, with varying degrees of third-party appeal.
Critical role of the neutrophil-associated high-affinity receptor for IgE in the pathogenesis of experimental cerebral malaria
Authors: Porcherie Adeline , Mathieu Cedric , Peronet Roger , Schneider Elke , Claver Julien , Commere Pierre-Henri , Kiefer-Biasizzo Hélène , Karasuyama Hajime , Milon Geneviève , Dy Michel , Kinet Jean-Pierre , Louis Jacques , Blank Ulrich , Mécheri Salaheddine
Published: October 2011

The role of the IgE–FcεRI complex in malaria severity in Plasmodium falciparum–hosting patients is unknown. We demonstrate that mice genetically deficient for the high-affinity receptor for IgE (FcεRIα-KO) or for IgE (IgE-KO) are less susceptible to experimental cerebral malaria (ECM) after infection with Plasmodium berghei (PbANKA). Mast cells and basophils, which are the classical IgE-expressing effector cells, are not involved in disease as mast cell–deficient and basophil-depleted mice developed a disease similar to wild-type mice. However, we show the emergence of an FcεRI+ neutrophil population, which is not observed in mice hosting a non–ECM-inducing PbNK65 parasite strain. Depletion of this FcεRI+ neutrophil population prevents ECM, whereas transfer of this population into FcεRIα-KO mice restores ECM susceptibility. FcεRI+ neutrophils preferentially home to the brain and induce elevated levels of proinflammatory cytokines. These data define a new pathogenic mechanism of ECM and implicate an FcεRI-expressing neutrophil subpopulation in malaria disease severity.
Regulation of neutrophils by interferon-γ limits lung inflammation during tuberculosis infection
Authors: Nandi Bisweswar , Behar Samuel M.
Published: October 2011

Resistance to Mycobacterium tuberculosis requires the host to restrict bacterial replication while preventing an over-exuberant inflammatory response. Interferon (IFN) γ is crucial for activating macrophages and also regulates tissue inflammation. We dissociate these two functions and show that IFN-γ−/− memory CD4+ T cells retain their antimicrobial activity but are unable to suppress inflammation. IFN-γ inhibits CD4+ T cell production of IL-17, which regulates neutrophil recruitment. In addition, IFN-γ directly inhibits pathogenic neutrophil accumulation in the infected lung and impairs neutrophil survival. Regulation of neutrophils is important because their accumulation is detrimental to the host. We suggest that neutrophilia during tuberculosis indicates failed Th1 immunity or loss of IFN-γ responsiveness. These results establish an important antiinflammatory role for IFN-γ in host protection against tuberculosis.
The movement of a solid in an incompressible perfect fluid as a geodesic flow
Authors: Glass Olivier , Sueur Franck
Published: October 2011

The motion of a rigid body immersed in an incompressible perfect fluid which occupies a three-dimensional bounded domain has recently been studied under its PDE formulation. In particular, classical solutions have been shown to exist locally in time. In this paper, following the celebrated result of Arnold concerning the case of a perfect incompressible fluid alone, we prove that these classical solutions are the geodesics of a Riemannian manifold of infinite dimension, in the sense that they are the critical points of an action, which is the integral over time of the total kinetic energy of the fluid-rigid body system.
Potential theory and a characterization of polynomials in complex dynamics
Authors: Okuyama Yûsuke , Stawiska Małgorzata
Published: October 2011

We obtain a characterization of polynomials among rational functions onP1\mathbb {P}^1from the point of view of complex dynamics and potential theory. This characterization generalizes a theorem of Lopes. Our proof applies both classical and (dynamically) weighted potential theory.
A review of the life cycles and life-history adaptations of pelagic tunicates to environmental conditions
Authors: Deibel Don , Lowen Ben
Published: October 2011

Deibel, D., and Lowen, B. 2012. A review of the life cycles and life-history adaptations of pelagic tunicates to environmental conditions. – ICES Journal of Marine Science, 69: 358–369. Phylogeny, life cycles, and life-history adaptations of pelagic tunicates to temperature and food concentration are reviewed. Using literature data on lifetime egg production and generation time of appendicularians, salps, and doliolids, rmax, the maximum rate of lifetime reproductive fitness, is calculated as a common metric of adaptation to environmental conditions. The rmax values are high for all three groups, ranging from ∼0.1 to 1.9 d−1, so population doubling times range from ∼8 h to 1 week. These high values of rmax are attributable primarily to short generation times, ranging from 2 to 50 d. Clearly, pelagic tunicates are adapted to event-scale (i.e. days to weeks) rather than seasonal-scale changes in environmental conditions. Although they are not closely related phylogenetically, all three groups have a unique life-history adaptation promoting high lifetime fitness. Appendicularians have late oocyte selection, salps are viviparous, and doliolids possess a polymorphic asexual phase. There has been little research on hermaphroditic appendicularians, on large oceanic salps, and on doliolids generally. Research is needed on factors regulating generation time, on the heritability of life-history traits, and on age- and size-specific rates of mortality.
Lidocaine Blocks the Hyperpolarization-activated Mixed Cation Current, I h, in Rat Thalamocortical Neurons
Authors: Putrenko Igor , Schwarz Stephan K. W.
Published: October 2011

Background

The mechanisms that underlie the supraspinal central nervous system effects of systemic lidocaine are poorly understood and not solely explained by Na(+) channel blockade. Among other potential targets is the hyperpolarization-activated cation current, I(h), which is blocked by lidocaine in peripheral neurons. I(h) is highly expressed in the thalamus, a brain area previously implicated in lidocaine's systemic effects. The authors tested the hypothesis that lidocaine blocks I(h) in rat thalamocortical neurons.

Methods

The authors conducted whole cell voltage- and current-clamp recordings in ventrobasal thalamocortical neurons in rat brain slices in vitro. Drugs were bath-applied. Data were analyzed with Student t tests and ANOVA as appropriate; α = 0.05.

Results

Lidocaine voltage-independently blocked I(h), with high efficacy and a half-maximal inhibitory concentration (IC(50)) of 72 μM. Lidocaine did not affect I(h) activation kinetics but delayed deactivation. The I(h) inhibition was accompanied by an increase in input resistance and membrane hyperpolarization (maximum, 8 mV). Lidocaine increased the latency of rebound low-threshold Ca(2+) spike bursts and reduced the number of action potentials in bursts. At depolarized potentials associated with the relay firing mode (>-60 mV), lidocaine at 600 μM concurrently inhibited a K(+) conductance, resulting in depolarization (7-10 mV) and an increase in excitability mediated by Na(+)-independent, high-threshold spikes.

Conclusions

Lidocaine concentration-dependently inhibited I(h) in thalamocortical neurons in vitro, with high efficacy and a potency similar to Na(+) channel blockade. This effect would reduce the neurons' ability to produce intrinsic burst firing and δ rhythms and thereby contribute to the alterations in oscillatory cerebral activity produced by systemic lidocaine in vivo.