bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrical transport properties in indium tin oxide films prepared by electron-beam evaporation
Authors: Liu X. D. , Jiang E. Y. , Zhang D. X.
Published: October 2008

Amorphous and polycrystalline indium tin oxide films have been prepared by electron-beam evaporation method. The amorphous films exhibit semiconductor behavior, while metallic conductivity is observed in the polycrystalline samples. The magnetoconductivities of the polycrystalline films are positive at low temperatures and can be well described by the theory of three-dimensional weak-localization effect. In addition, the electron phase-breaking rate is proportional to T3/2. Comparing the experimental results with theory, we find that the electron-electron scattering is the dominant destroyer of the constructive interference in the films. In addition, the Coulomb interaction is the main contribution to the nontrivial corrections for the electrical conductivity at low temperatures.
Diffraction of cholesteric liquid crystal gratings probed by monochromatic light from 450 to 750 nm
Authors: Hung Wen-Chi , Cheng Wood-Hi , Liu Tung-Kia , Jiang I-Min , Tsai Ming-Shan , Yeh Pochi
Published: October 2008

We investigated both theoretically and experimentally the diffraction property of cholesteric liquid crystals (CLCs) in the configuration of transmission grating. The CLCs are treated as birefringent index gratings whose diffraction property is strongly dependent on the polarization state of the incident beam. In our experimental studies, the CLC index gratings are constructed by applying an electric voltage to liquid crystal cell. The grating is probed by a monochromatic light in spectral range from 450 to 750 nm and the measured diffraction efficiency approximately agrees with the theoretical predictions. The dependence of polarization and wavelength of polarized monochromatic light may possibly lead to a light switch in optical communication system.
Supercollimation in photonic crystals composed of silicon rods
Authors: Shih Ta-Ming , Kurs André , Dahlem Marcus , Petrich Gale , Soljačić Marin , Ippen Erich , Kolodziejski Leslie , Hall Katherine , Kesler Morris
Published: October 2008

Supercollimation is the propagation of light without diffraction using the properties of photonic crystals. We present the first experimental demonstration of supercollimation in a planar photonic crystal composed of nanoscale rods. Supercollimation was observed over distances of up to 1000 lattice periods.
Patterns of connectivity between the Lake Eyre and Gulf drainages, Australia: a phylogeographic approach
Authors: Masci Kate D. , Ponniah Mark , Hughes Jane M.
Published: October 2008

Historical barriers to dispersal in freshwater environments can be detected in the genetic structure of organisms living within these environments. Over time, it is possible that a barrier for freshwater organisms becomes passable, allowing gene flow between adjacent populations. The Lake Eyre and Gulf of Carpentaria Basins are adjacent drainages in northern Queensland. Low topography and large-scale flooding events make it possible that connectivity events may have occurred between the drainages throughout history. Documented geological evidence also suggests historical connectivity between the basins in the Pliocene. The present study looked at two widely distributed species, the freshwater fish Nematalosa erebi and the freshwater prawn Macrobrachium australiense, and used mitochondrial sequence data to assess past connectivity between the basins and estimate the timing of these events. Both species showed significant divergence across the drainage divide. There was evidence of two fragmentation events in the N. erebi data and divergence estimates for these events were 160 000 and 350 000 years ago. It was estimated that there has been no dispersal of M. australiense across the drainage divide for over one million years. The discordant evolutionary histories observed suggest that the patterns reflect recent historical environmental events and life-history differences between the two species.
Shaping a bacterial genome by large chromosomal replacements, the evolutionary history of
Streptococcus agalactiae
Authors: Brochet Mathieu , Rusniok Christophe , Couvé Elisabeth , Dramsi Shaynoor , Poyart Claire , Trieu-Cuot Patrick , Kunst Frank , Glaser Philippe
Published: October 2008

Bacterial populations are subject to complex processes of diversification that involve mutation and horizontal DNA transfer mediated by transformation, transduction, or conjugation. Tracing the evolutionary events leading to genetic changes allows us to infer the history of a microbe. Here, we combine experimental and
in silico
approaches to explore the forces that drive the genome dynamics of
Streptococcus agalactiae
, the leading cause of neonatal infections. We demonstrate that large DNA segments of up to 334 kb of the chromosome of
S. agalactiae
can be transferred through conjugation from multiple initiation sites. Consistently, a genome-wide map analysis of nucleotide polymorphisms among eight human isolates demonstrated that each chromosome is a mosaic of large chromosomal fragments from different ancestors suggesting that large DNA exchanges have contributed to the genome dynamics in the natural population. The analysis of the resulting genetic flux led us to propose a model for the evolutionary history of this species in which clonal complexes of clinical importance derived from a single clone that evolved by exchanging large chromosomal regions with more distantly related strains. The emergence of this clone could be linked to selective sweeps associated with the reduction of genetic diversity in three regions within a large panel of human isolates. Up to now sex in bacteria has been assumed to involve mainly small regions; our results define
S. agalactiae
as an alternative paradigm in the study of bacterial evolution.
Dissociation of
in vitro
DNA deamination activity and physiological functions of AID mutants
Authors: Shivarov Velizar , Shinkura Reiko , Honjo Tasuku
Published: October 2008

Activation-induced cytidine deaminase (AID) is essential for the DNA cleavage that initiates both somatic hypermutation (SHM) and class switch recombination (CSR) of the Ig gene. Two alternative mechanisms of DNA cleavage by AID have been proposed: RNA editing and DNA deamination. In support of the latter, AID has DNA deamination activity in cell-free systems that is assumed to represent its physiological function. To test this hypothesis, we generated various mouse AID mutants and compared their DNA deamination, CSR, and SHM activities. Here, we compared DNA deamination, CSR, and SHM activities of various AID mutants and found that most of their CSR or SHM activities were disproportionate with their DNA deamination activities. Specifically, we identified a cluster of mutants (H48A, L49A, R50A, and N51A) with low DNA deamination activity but relatively intact CSR activity. Of note is an AID mutant (N51A) that retained CSR function but lost DNA deamination activity. In addition, an APOBEC1 mutation at N57, homologous to N51 of AID, also abolished DNA deamination activity but retained RNA editing activity. These results indicate that DNA deamination activity does not represent the physiological function of AID.
Transient and selective overexpression of D
2
receptors in the striatum causes persistent deficits in conditional associative learning
Authors: Bach Mary-Elizabeth , Simpson Eleanor H. , Kahn Lora , Marshall John J. , Kandel Eric R. , Kellendonk Christoph
Published: October 2008

Cognitive deficits in schizophrenia are thought to derive from a hypofunction of the prefrontal cortex (PFC), but the origin of the hypofunction is unclear. To explore the nature of this deficit, we genetically modified mice to model the increase in striatal dopamine D
2
receptors (D
2
Rs) observed in patients with schizophrenia. Previously, we reported deficits in spatial working memory tasks in these mice, congruent with the working memory deficits observed in schizophrenia. However, patients with schizophrenia suffer from deficits in many executive functions, including associative learning, planning, problem solving, and nonspatial working memory. We therefore developed operant tasks to assay two executive functions, conditional associative learning (CAL) and nonspatial working memory. Striatal D
2
R-overexpressing mice show a deficit in CAL because of perseverative behavior, caused by interference from the previous trial. D
2
R up-regulation during development was sufficient to cause this deficit, because switching off the transgene in adulthood did not rescue the phenotype. We validated prefrontal dependency of CAL by using neurotoxic lesions. Lesions of the medial PFC including the anterior cingulate, infralimbic, and prelimbic cortices impair CAL because of increased interference from previously rewarded trials, exactly as observed in D
2
R transgenic mice. In contrast, lesions restricted to the infralimbic and prelimbic cortices have no effect on CAL but impair performance in the nonspatial working memory task. These assays not only give us insight into how excess striatal D
2
Rs affect cognition but also provide tools for studying cognitive endophenotypes in mice.
Parkinsonism and impaired axonal transport in a mouse model of frontotemporal dementia
Authors: Ittner Lars M. , Fath Thomas , Ke Yazi D. , Bi Mian , van Eersel Janet , Li Kong M. , Gunning Peter , Götz Jürgen
Published: October 2008

Frontotemporal dementia (FTD) is characterized by cognitive and behavioral changes and, in a significant subset of patients, Parkinsonism. Histopathologically, FTD frequently presents with tau-containing lesions, which in familial cases result from mutations in the
MAPT
gene encoding tau. Here we present a novel transgenic mouse strain (K3) that expresses human tau carrying the FTD mutation K369I. K3 mice develop a progressive histopathology that is reminiscent of that in human FTD with the K369I mutation. In addition, K3 mice show early-onset memory impairment and amyotrophy in the absence of overt neurodegeneration. Different from our previously generated tau transgenic strains, the K3 mice express the transgene in the substantia nigra (SN) and show an early-onset motor phenotype that reproduces Parkinsonism with tremor, bradykinesia, abnormal gait, and postural instability. Interestingly, motor performance of young, but not old, K3 mice improves upon L-dopa treatment, which bears similarities to Parkinsonism in FTD. The early-onset symptoms in the K3 mice are mechanistically related to selectively impaired anterograde axonal transport of distinct cargos, which precedes the loss of dopaminergic SN neurons that occurs in aged mice. The impaired axonal transport in SN neurons affects, among others, vesicles containing the dopamine-synthesizing enzyme tyrosine hydroxylase. Distinct modes of transport are also impaired in sciatic nerves, which may explain amyotrophy. Together, the K3 mice are a unique model of FTD-associated Parkinsonism, with pathomechanistic implications for the human pathologic process.
A comparison of different heart rate deflection methods to predict the anaerobic threshold
Authors: Carey Daniel G. , Pliego German J. , Raymond Robert L.
Published: October 2008

There is perhaps no greater controversy in exercise physiology than the validity, or lack thereof, of the heart rate breakpoint theory in general, and the Conconi test in particular, in assessing the anaerobic threshold. Three heart rate breakpoint methods have been proposed as methods of detecting the anaerobic threshold have appeared in the literature: (1) a breakpoint in linearity of the heart rate–work rate relationship (heart rate breakpoint); (2) a log function curve of the heart rate–work rate relationship (log function); and (3) a combination of linear regression and logarithmic function of the heart rate–work rate relationship (log‐linear). The main aim of this study was to assess the validity of these methods compared with that of gas analysis assessment of the anaerobic threshold. This was a descriptive study of 115 endurance athletes undergoing simultaneous gas analysis and heart rate determination during incremental exercise to exhaustion. The participants were 115 competitive cyclists and/or triathletes (71 males: mean age 38.5 years, s=6.2; 44 females: mean age 37.8 years, s=5.1). Incremental exercise testing to exhaustion was performed on an electrically braked cycle ergometer, commencing at 25 W and increasing by 25 W · min−1 to volitional fatigue. Heart rate was recorded each minute and at exhaustion. Gas analysis was performed using breath‐by‐breath analysis with 10‐s averaging. The anaerobic threshold based on ventilatory parameters was used as the criterion test. Compared with the criterion threshold, no significant differences were observed for the heart rate breakpoint (t=1.12, P=0.268) or log function (t=0.0, P=0.998) methods. However, the log‐linear method (t=2.25, P=0.026) significantly overestimated the anaerobic threshold. Although two of the three heart rate methods were validated in this study, the relatively large total errors for these methods (13.7 beats · min−1 for heart rate breakpoint, 12.5 beats · min−1 for log function, and 14.3 beats · min−1 for log‐linear) indicate that they would have little practical value.
An elite endurance athlete's recovery from underperformance aided by a multidisciplinary sport science support team
Authors: Gustafsson Henrik , Holmberg Hans‐Christer , Hassmén Peter
Published: October 2008

Overload training resulting in an overreached state is common in elite sports, and if undetected can develop into an overtraining syndrome. This risk is accentuated by the lack of reliable measures of overreaching. Coaches and scientists therefore have to use a combination of tests in the monitoring process. This article presents a case study of the recovery from underperformance of a young elite endurance athlete and the work of a multidisciplinary sport science support team. When it was determined that the athlete's performance had deteriorated, and that this was due solely to the stress of training, training load was radically reduced for a period of 14 days. A combination of physiological, biochemical, and psychological measurements were then used to monitor the recovery process. The purpose of this article is to describe how coaches and sport science teams can help in monitoring training and recovery in practical settings, allowing detection of the early signs of overreaching before a more serious overtraining syndrome develops.
Psychomotor speed is related to perceived performance in rowers
Authors: Nederhof Esther , Visscher Chris , Lemmink Koen
Published: October 2008

The goal of the present study was to determine if psychomotor speed is related to perceived performance. It was hypothesized that lower perceived performance was related to longer reaction times. A total of 85 measurements were taken in 26 varsity rowers (mean age 21.3 years, s=1.6) on five occasions over the course of the season. Perceived performance was measured with the “Reduced Sense of Accomplishment” scale of the Athlete Burnout Questionnaire. Reaction times were measured with the finger pre‐cueing task and with the action and reaction modes of the determination test. The complex structured data were analysed with multi‐level modelling. Random intercept linear models showed that perceived performance was not related to reaction times on the finger pre‐cueing task. Perceived performance significantly predicted reaction times on the action and reaction modes of the determination test. In rowers who were not selected for the team after completing two measurement sessions, this relationship did not exist in the action mode; deselection was a moderator. Thus, a significant relationship between reaction times on the determination test and perceived performance was observed. It was concluded that the determination test could be a useful tool to monitor rowers’ responses to training, although several issues should be resolved before it can be used in practice.
The effect on heart rate variability of acclimatization to a humid, hot environment after a transition across five time zones in elite junior rowers
Authors: Dranitsin Oleg V.
Published: October 2008

The aim of this study was to examine the simultaneous effect on heart rate variability (HRV) of acclimatization to a hot, humid environment and a transition of five time zones in elite junior rowers. Thirteen rowers (12 males and 1 female) participated in the study. Each rower was monitored during training camps in temperate and in humid, hot conditions before and during the Junior Rowing World Championship. All participants recorded the lengths of high‐intensity training sessions, and R‐R (the time between the R peaks of consecutive QRS complexes) intervals were measured every morning after awakening. Compared with baseline values taken during training before the transition to the new time zone and climate, HRV indices during first 3 days of acclimatization remained unchanged. On the fourth and fifth days of acclimatization, significant decreases in measures of heart rate variability in the standing position were observed. Beginning from the sixth day of acclimatization and for all subsequent days, the HRV indices, while standing, returned to baseline values and were not significantly different from baseline. Despite this, there were no significant changes in HRV measures in a supine position until the eighth day of acclimatization. R‐R intervals decreased and mean heart rate increased significantly (P<0.001) during days 8–10 of acclimatization. In conclusion, major physiological adaptation of HRV indices in the standing position during acclimatization to a humid, hot environment, with a transition across five time zones, occurs within the first 5 days in elite athletes before returning to baseline. Indices of heart rate variability in the supine position correlate with the length of high‐intensity training sessions on the previous day.
Science and the Gaelic sports: Gaelic football and hurling
Authors: Reilly Thomas , Collins Kieran
Published: October 2008

The two major sports indigenous to Ireland are Gaelic football and hurling. Both are 15‐a‐side field games played on a pitch 40% longer than a soccer field. They are firmly linked to a nationalist tradition and have by far the highest participation rates in sports in the country. Both games make multiple demands on participants due to their free‐flowing nature and quick movement of play from end to end of the pitch. Hurling calls for hand–eye coordination and skilled use of the hurling stick in hitting and blocking the ball. Fitness characteristics mirror game demands. Participants at elite level in both games display high aerobic power, the footballers tending to be stronger in the upper body and better in vertical jumping. Gaelic footballers in particular match the fitness characteristics of professional soccer players, except for sprinting speed. Less attention has been paid to female participants, especially in camogie, the female version of hurling. Despite their amateur status, and due to the popularity of the sports and the training regimens adopted by players, the games have garnered sports science support systems for elite performers. Support personnel benefit from a generic knowledge base as well as a burgeoning research agenda targeted at the Gaelic games.
LKB1 induces apical trafficking of Silnoon, a monocarboxylate transporter, in Drosophila melanogaster
Authors: Jang Cholsoon , Lee Gina , Chung Jongkyeong
Published: October 2008

Silnoon (Sln) is a monocarboxylate transporter (MCT) that mediates active transport of metabolic monocarboxylates such as butyrate and lactate. Here, we identify Sln as a novel LKB1-interacting protein using Drosophila melanogaster genetic modifier screening. Sln expression does not affect cell cycle progression or cell size but specifically enhances LKB1-dependent apoptosis and tissue size reduction. Conversely, down-regulation of Sln suppresses LKB1-dependent apoptosis, implicating Sln as a downstream mediator of LKB1. The kinase activity of LKB1 induces apical trafficking of Sln in polarized cells, and LKB1-dependent Sln trafficking is crucial for triggering apoptosis induced by extracellular butyrate. Given that LKB1 functions to control both epithelial polarity and cell death, we propose Sln is an important downstream target of LKB1.
Darrieussecq's Mind
Authors: Kemp Simon
Published: October 2008

From
Naissance des fantômes
onwards, Marie Darrieussecq's representation of the self draws heavily on the materialist mind/brain model of cognitive science. Her fiction makes use of the discipline's discourse with and against the grain, creating micro-narratives of the mind's surface level and present moment which contrast sharply with more familiar psychoanalytic perspectives. Narrative form in Darrieussecq, I argue, can be characterized as a stream-of-consciousness, which, while failing to conform to the literary model set by Dujardin and Joyce, is in fact closer to the original psychological conception of the term. The article concludes by examining Darrieussecq's model of the mind in the context of France's current ‘guerre des psys’ between cognitive science and psychoanalysis.
The Judgement of Experience: Reading and Seeing in Diderot's
Lettre sur les aveugles
Authors: Tunstall Kate E.
Published: October 2008

In addition to the usual question underlying empiricist epistemology, namely how we are to judge our sensory experience, Diderot raises the question as to how we are to judge our reading experience, explicitly asking ‘Madame’, the reader, to come to a view as to whether his presentation of the blind man of Puiseaux as a real person is persuasive or not. This essay, building on an earlier article published in
French Studies Bulletin
(2006) which provided original evidence as to the historical reality of the blind man, revisits the question as to his imaginary nature by arguing for the intertextual presence of Montaigne's description of ‘un gentil-homme de bonne maison, aveugle nay’ in the ‘Apologie de Raimond Sebond’. The presence of this intertext, which has not been identified as such before, suggests that in order accurately to judge his or her reading experience the reader requires knowledge of the
Lettre
's literary and philosophical context, a view which is echoed in a different form in Diderot's discussion of Molyneux's Question. In Diderot's view, the woman who sees for the first time will be unable to judge her sensory experience and unable therefore to answer Molyneux's Question, if she does not have knowledge of the question's metaphysical and mathematical background. Where other readers have recently argued that the
Lettre
emphasizes the importance of language in understanding experience, this essay thus argues that the
Lettre
also makes a case for the importance of a literary and philosophical education in our understanding and judgement of experience, be it visual or textual.
Opposites and Identities: Maurice Scève's
Délie
and Charles de Bovelles's
Ars oppositorum
Authors: Banks Kathryn
Published: October 2008

In early sixteenth-century France, uses and conceptions of opposition were varied and shifting. This article analyses some complex and apparently paradoxical notions of opposites and identities found in two very different texts, Charles de Bovelles's
Ars oppositorum
(1511) and Maurice Scève's
Délie
(1544), examples of Latin prose philosophy and vernacular love lyric respectively. I argue that Scève's poetry, like Bovelles's theory, reflects profoundly upon opposition, difference and identity. In particular, I focus in the
Délie
upon relations of opposition and similarity between ‘microcosm’ and ‘macrocosm’, evoked through the poet's use of the ‘jealous sun’ topos. Bovelles explores models of opposition drawn from contrasting generic contexts, including Aristotelian logic and Cusa's mystical theology. However, both the
Délie
and the
Ars
diverge in striking ways from strict categorizations of difference and identity (as typified by traditional dialectic). Both think through the relationships between antithetical modes of difference and other kinds, attempting to imagine even the co-existence of difference and identity. Both also present ways in which one relation of difference inflects another, and thus offer particularly complex accounts of dynamic interactions between opposites.
Finding friends and enemies in an enemies-only network: A graph diffusion kernel for predicting novel genetic interactions and co-complex membership from yeast genetic interactions
Authors: Qi Yan , Suhail Yasir , Lin Yu-yi , Boeke Jef D. , Bader Joel S.
Published: October 2008

The yeast synthetic lethal genetic interaction network contains rich information about underlying pathways and protein complexes as well as new genetic interactions yet to be discovered. We have developed a graph diffusion kernel as a unified framework for inferring complex/pathway membership analogous to “friends” and genetic interactions analogous to “enemies” from the genetic interaction network. When applied to theSaccharomyces cerevisiaesynthetic lethal genetic interaction network, we can achieve a precision around 50% with 20% to 50% recall in the genome-wide prediction of new genetic interactions, supported by experimental validation. The kernels show significant improvement over previous best methods for predicting genetic interactions and protein co-complex membership from genetic interaction data.
Dispensability of mammalian DNA
Authors: McLean Cory , Bejerano Gill
Published: October 2008

In the lab, the cis-regulatory network seems to exhibit great functional redundancy. Many experiments testing enhancer activity of neighboring cis-regulatory elements show largely overlapping expression domains. Of recent interest, mice in which cis-regulatory ultraconserved elements were knocked out showed no obvious phenotype, further suggesting functional redundancy. Here, we present a global evolutionary analysis of mammalian conserved nonexonic elements (CNEs), and find strong evidence to the contrary. Given a set of CNEs conserved between several mammals, we characterize functional dispensability as the propensity for the ancestral element to be lost in mammalian species internal to the spanned species tree. We show that ultraconserved-like elements are over 300-fold less likely than neutral DNA to have been lost during rodent evolution. In fact, many thousands of noncoding loci under purifying selection display near uniform indispensability during mammalian evolution, largely irrespective of nucleotide conservation level. These findings suggest that many genomic noncoding elements possess functions that contribute noticeably to organism fitness in naturally evolving populations.
Unraveling ancient hexaploidy through multiply-aligned angiosperm gene maps
Authors: Tang Haibao , Wang Xiyin , Bowers John E. , Ming Ray , Alam Maqsudul , Paterson Andrew H.
Published: October 2008

Large-scale (segmental or whole) genome duplication has been recurring in angiosperm evolution. Subsequent gene loss and rearrangements further affect gene copy numbers and fractionate ancestral gene linkages across multiple chromosomes. The fragmented “multiple-to-multiple” correspondences resulting from this distinguishing feature of angiosperm evolution complicates comparative genomic studies. Using a robust computational framework that combines information from multiple orthologous and duplicated regions to construct local syntenic networks, we show that a shared ancient hexaploidy event (or perhaps two roughly concurrent genome fusions) can be inferred based on the sequences from several divergent plant genomes. This “paleo-hexaploidy” clearly preceded the rosid–asterid split, but it remains equivocal whether it also affected monocots. The model resulting from our multi-alignments lays the foundation for approximating the number and arrangement of genes in the last universal common ancestor of angiosperms. Comparative analysis of inferred homologous genes derived from this model shows patterns of preferential gene retention or loss after polyploidy and reveals large variability of nucleotide substitution rates among plant nuclear genomes.
The NO-cGMP-PKG signaling pathway regulates synaptic plasticity and fear memory consolidation in the lateral amygdala via activation of ERK/MAP kinase
Authors: Ota Kristie T. , Pierre Vicki J. , Ploski Jonathan E. , Queen Kaila , Schafe Glenn E.
Published: October 2008

Recent studies have shown that nitric oxide (NO) signaling plays a crucial role in memory consolidation of Pavlovian fear conditioning and in synaptic plasticity in the lateral amygdala (LA). In the present experiments, we examined the role of the cGMP-dependent protein kinase (PKG), a downstream effector of NO, in fear memory consolidation and long-term potentiation (LTP) at thalamic and cortical input pathways to the LA. In behavioral experiments, rats given intra-LA infusions of either the PKG inhibitor Rp-8-Br-PET-cGMPS or the PKG activator 8-Br-cGMP exhibited dose-dependent impairments or enhancements of fear memory consolidation, respectively. In slice electrophysiology experiments, bath application of Rp-8-Br-PET-cGMPS or the guanylyl cyclase inhibitor LY83583 impaired LTP at thalamic, but not cortical inputs to the LA, while bath application of 8-Br-cGMP or the guanylyl cyclase activator YC-1 resulted in enhanced LTP at thalamic inputs to the LA. Interestingly, YC-1-induced enhancement of LTP in the LA was reversed by concurrent application of the MEK inhibitor U0126, suggesting that the NO-cGMP-PKG signaling pathway may promote synaptic plasticity and fear memory formation in the LA, in part by activating the ERK/MAPK signaling cascade. As a test of this hypothesis, we next showed that rats given intra-LA infusion of the PKG inhibitor Rp-8-Br-PET-cGMPS or the PKG activator 8-Br-cGMP exhibit impaired or enhanced activation, respectively, of ERK/MAPK in the LA after fear conditioning. Collectively, our findings suggest that an NO-cGMP-PKG-dependent form of synaptic plasticity at thalamic input synapses to the LA may underlie memory consolidation of Pavlovian fear conditioning, in part, via activation of the ERK/MAPK signaling cascade.
An open study of antibiotics for the treatment of pre‐pouch ileitis following restorative proctocolectomy with ileal pouch–anal anastomosis
Authors: MCLAUGHLIN S. D. , CLARK S. K. , BELL A. J. , TEKKIS P. P. , CICLITIRA P. J. , NICHOLLS R. J.
Published: October 2008

Background  Pre‐pouch ileitis is a recently described condition which may occur following restorative proctocolectomy. Its aetiology remains unknown and only one study has reported the effect of treatment. We report a series of fourteen patients treated and followed up with repeat pouchoscopy.

Aim  To study the effectiveness of antibiotics for the treatment of pre‐pouch ileitis following restorative proctocolectomy with ileal pouch–anal anastomosis.

Methods  Fourteen consecutive patients with symptomatic pre‐pouch ileitis were treated with ciprofloxacin 500 mg b.d. and metronidazole 400 mg b.d. for 28 days. All had concurrent pouchitis. Symptomatic, endoscopic and histological assessment was performed before and following treatment using the pouchitis disease activity index (PDAI). Symptomatic remission was defined as a score of 0 in the clinical component of the PDAI.

Results  Twelve (86%) patients experienced symptomatic remission. Stool frequency fell from a median of 12 (range 8–20) to 6 (4–17) (P = 0.002). There was a significant reduction in the anatomical length of pre‐pouch ileitis with nine (64%) patients having either a resolution or a reduction in length of pre‐pouch ileitis from a median of 10 cm (range 3–20 cm) to a median of 1 cm (range 0–10 cm) (P = 0.007).

Conclusion  Combination antibiotic therapy in this uncontrolled study appears effective in reducing the length of pre‐pouch ileitis and in inducing symptomatic remission in most patients whether or not its extent is reduced.
Expression of FcγRs and mCD14 on polymorphonuclear neutrophils and monocytes may determine periodontal infection
Authors: Nicu E A , van der Velden U , Everts V , Loos B G
Published: October 2008

Variance in expression of receptors for immunoglobulin G (FcγRs), complement (CR3) and lipopolysaccharide (mCD14) on polymorphonuclear neutrophils (PMNs) and monocytes might affect susceptibility for infection with certain pathogens in periodontitis, a chronic infectious disease of tooth-supportive tissues. Levels of FcγRI, IIa, III, CR3 and mCD14 on PMNs and monocytes were measured in 19 periodontitis patients and 18 healthy controls. Subgingival infection with Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) was determined. Activation of PMNs and monocytes in response to stimulation with Aa and Pg was assessed by means of change in mCD14 expression. Periodontitis is associated with an enrichment of the FcγRIII+ monocytes (P = 0·015) with concomitant low mCD14 (P = 0·001). Unadjusted data showed that the subjects culture-positive for Aa (Aa+) had significantly lower expression of monocytic FcγRI (P = 0·005) and FcγRIIa (P = 0·015) than Pg+ subjects. The FcγRI was still lower on monocytes from Aa+ subjects after adjusting for the background factors (P = 0·037). PMNs from Aa+ subjects responded in a hyper-reactive manner, in particular when stimulated with Aa (P = 0·011). Lower FcγRs expression by monocytes is related to a higher susceptibility of a subject to become infected with Aa. The higher proportion of FcγRIII+ monocytes may be involved in the chronicity of this condition. Hyper-reactive PMNs in Aa+ subjects may contribute to accelerated breakdown of tooth-supportive tissues.
Attenuation of monocyte proinflammatory cytokine responses toNeisseria meningitidisin children by erythropoietin
Authors: Schultz C , Zimmer J , Härtel C , Rupp J , Temming P , Strunk T
Published: October 2008

Meningococcal disease is a leading infectious cause of death in children in industrialized countries. The induction of high levels of proinflammatory cytokines has been implicated in the pathogenesis of Neisseria meningitidis-related multi-organ failure. Here, we demonstrate that N. meningitidis serotypes A and B induce significantly higher levels of tumour necrosis factor (TNF)-α positive cells in vitro in infants and young children compared with adults (serotype A/B; infants: 64·9%/63·9%; children: 77·8%/64·3% versus adults: 27·7%/32%; P < 0·005). Serotype A induces also higher levels of interleukin (IL)-6 positive cells in neonates and infants compared with adults (serotype A; newborn 55·4%; infants 58·8% versus adults 49%; P < 0·05). Treatment with human recombinant erythropoietin in vitro resulted in significant attenuation of the N. meningitidis-induced proinflammatory response in all age groups (reduction rate of erythropoietin for IL-6 after stimulation with serotype B: newborn 28%, infants 15%, children 23% and adults 28% and for TNF-α after stimulation with serotype B: newborn 27%, infants 22%, children 20% and adults 28%; P < 0·05). We conclude that (i) Neisseria meningitidis induces a higher TNF-α response in infants and children compared with adults and (ii) erythropoietin was able to attenuate IL-6 and TNF-α production in all investigated age groups. These data may explain the high incidence of meningococcal infection in infants and makes erythropoietin a potentially attractive candidate for interventional strategies in an otherwise devastating course of the disease.
Skew in T cell receptor usage with polyclonal expansion in lesions of oral lichen planus without hepatitis C virus infection
Authors: Gotoh A , Hamada Y , Shiobara N , Kumagai K , Seto K , Horikawa T , Suzuki R
Published: October 2008

Oral lichen planus (OLP) is a refractory disorder of the oral mucosa. Its predominant symptoms are pain and haphalgesia that impair the quality of life of patients. OLP develops via a T cell-mediated immune process. Here, we examined the characteristics of the infiltrating T cells in terms of the T cell receptor (TCR) repertoires, T cell clonality, T cell phenotypes and cytokine production profiles. TCR repertoire analyses and CDR3 size spectratyping were performed using peripheral blood mononuclear cells (PBMCs) and tissue specimens of OLP biopsies from 12 patients. The cytokine expression profiles and T cell phenotypes were measured by real-time quantitative polymerase chain reaction. We observed that there were skewed TCR repertoires in the tissue samples (TCRVA8-1, VA22-1, VB2-1, VB3-1 and VB5-1) and PBMCs (TCRVA8-1, VB2-1, VB3-1 and VB5-1) from OLP patients. Furthermore, the CDR3 distributions in the skewed TCR subfamilies exhibited polyclonal patterns. We observed increases in CD4+ T lymphocytes, interleukin (IL)-5, tumour necrosis factor (TNF)-α and human leucocyte antigen D-related in the OLP tissue specimens. Taken together, the present results suggest that T cells bearing these TCRs are involved in the pathogenesis of OLP, and that IL-5 and TNF-α may participate in its inflammatory process.
The demography of nurses and patients on acute psychiatric wards in England
Authors: Bowers Len , Jones Julia , Simpson Alan
Published: October 2008

Aims and objectives. To describe the ethnic and demographic composition of staff and patients on acute psychiatric wards in England.

Background. A significant proportion of the UK population (7·6%) belong to an ethnic minority and there are concerns that ethnic minority patients are not well served by psychiatry, in particular that they are subject to excessive force and coercion.

Design. Survey of a random sample of psychiatric wards in three regions.

Methods. A survey was conducted of staff (n = 1536) and patients (n = 11 128) on 136 acute admission psychiatric wards.

Results. Ethnic minority patients were more likely to be admitted with a diagnosis of schizophrenia, younger, more likely to be admitted for a risk of harm to others and more likely to be legally detained. The association between ethnic minority status and detention remains, even when risk, age, gender and diagnosis are taken into account. Ethnic minority patients come from areas of greater social deprivation and fragmentation. Ethnic concordance between staff and patients varies, but the greatest difference is found in London where the proportion of minority staff is greater than the proportion of minority patients.

Conclusions. There continues to be evidence that ethnic minority patients are subject to an excessive amount of legal coercion in English mental health services. However, the proportion of staff belonging to an ethnic minority is greater than the proportion of patients.

Relevance to clinical practice. Solutions to the problem of excessive use of legal coercion with ethnic minority patients need to be found. Changes of recruitment strategies are required if concordance is to be achieved.
New insights into the cellular organization of the RNA processing and degradation machinery of Escherichia coli
Authors: Taghbalout Aziz , Rothfield Lawrence
Published: October 2008

Ribonuclease E (RNase E) is a component of the Escherichia coli RNA degradosome, a multiprotein complex that also includes RNA helicase B (RhlB), polynucleotide phosphorylase (PNPase) and enolase. The degradosome plays a key role in RNA processing and degradation. The degradosomal proteins are organized as a cytoskeletal‐like structure within the cell that has been thought to be associated with the cytoplasmic membrane. The article by Khemici et al. in the current issue of Molecular Microbiology reports that RNase E can directly interact with membrane phospholipids in vitro. The RNase E–membrane interaction is likely to play an important role in the membrane association of the degradosome system. These findings shed light on important but largely unexplored aspects of cellular structure and function, including the organization of the RNA processing machinery of the cell and of bacterial cytoskeletal elements in general.
Application of magnetic resonance imaging to measure fasting and postprandial volumes in humans
Authors: Fidler J. , Bharucha A. E. , Camilleri M. , Camp J. , Burton D. , Grimm R. , Riederer S. J. , Robb R. A. , Zinsmeister A. R.
Published: October 2008

Abstract  Our aims were to measure the gastric volume response in excess of ingested meal volume (i.e. gastric accommodation), contribution of swallowed air to this excess, day‐to‐day variability of gastric volumes measured by MRI and their relationship to volumes measured by single‐photon‐emission computed tomography (SPECT). In 20 healthy volunteers, fasting and postprandial gastric volumes were measured after technetium99m‐pertechnetate labeling of the gastric mucosa by SPECT and separately by MRI, using 3D gradient echo and 2D half‐Fourier acquisition single‐shot turbo spin echo (HASTE) sequences. Ten of these subjects had a second MRI exam to assess intra‐individual variation. Thereafter, another 10 subjects had two MRI studies during which they ingested the nutrient in 30 or 150 mL aliquots. During MRI, the postprandial gastric volume change exceeded the ingested meal volume by 106 ± 12 mL (Mean ± SEM). The HASTE and gradient echo sequences distinguished air from fluid under fasting and postprandial conditions respectively. This postprandial excess mainly comprised air (61 ± 5 mL), which was not significantly different when ingested as 30 or 150 mL aliquots. Fasting and postprandial gastric volumes measured by MRI were generally reproducible within subjects. During SPECT, postprandial volumes increased by 158 ± 18 mL; gastric volumes measured by SPECT were higher than MRI. MRI measures gastric volumes with acceptable performance characteristics; the postprandial excess primarily consists of air, which is not affected by the mode of ingestion. Gastric volumes are technique specific and differ between MRI and SPECT.
Human Hendra virus infection causes acute and relapsing encephalitis
Authors: Wong K. T. , Robertson T. , Ong B. B. , Chong J. W. , Yaiw K. C. , Wang L. F. , Ansford A. J. , Tannenberg A.
Published: October 2008

Aim: To study the pathology of two cases of human Hendra virus infection, one with no clinical encephalitis and one with relapsing encephalitis. Methods: Autopsy tissues were investigated by light microscopy, immunohistochemistry and in situ hybridization. Results: In the patient with acute pulmonary syndrome but not clinical acute encephalitis, vasculitis was found in the brain, lung, heart and kidney. Occasionally, viral antigens were demonstrated in vascular walls but multinucleated endothelial syncytia were absent. In the lung, there was severe inflammation, necrosis and viral antigens in type II pneumocytes and macrophages. The rare kidney glomerulus showed inflammation and viral antigens in capillary walls and podocytes. Discrete necrotic/vacuolar plaques in the brain parenchyma were associated with antigens and viral RNA. Brain inflammation was mild although CD68+ microglia/macrophages were significantly increased. Cytoplasmic viral inclusions and antigens and viral RNA in neurones and ependyma suggested viral replication. In the case of relapsing encephalitis, there was severe widespread meningoencephalitis characterized by neuronal loss, macrophages and other inflammatory cells, reactive blood vessels and perivascular cuffing. Antigens and viral RNA were mainly found in neurones. Vasculitis was absent in all the tissues examined. Conclusions: The case of acute Hendra virus infection demonstrated evidence of systemic infection and acute encephalitis. The case of relapsing Hendra virus encephalitis showed no signs of extraneural infection but in the brain, extensive inflammation and infected neurones were observed. Hendra virus can cause acute and relapsing encephalitis and the findings suggest that the pathology and pathogenesis are similar to Nipah virus infection.
Non‐invasive topology analysis of membrane proteins in the secretory pathway
Authors: Brach Thorsten , Soyk Sebastian , Müller Christopher , Hinz Giselbert , Hell Rüdiger , Brandizzi Federica , Meyer Andreas J.
Published: October 2008

We present a novel method to experimentally visualize in vivo the topology of transmembrane proteins residing in the endoplasmic reticulum (ER) membrane or passing through the secretory pathway on their way to their final destination. This approach, so‐called redox‐based topology analysis (ReTA), is based on fusion of transmembrane proteins with redox‐sensitive GFP (roGFP) and ratiometric imaging. The ratio images provide direct information on the orientation of roGFP relative to the membrane as the roGFP fluorescence alters with changes in the glutathione redox potential across the ER membrane. As proof of concept, we produced binary read‐outs using oxidized roGFP inside the ER lumen and reduced roGFP on the cytosolic side of the membrane for both N‐ and C‐terminal fusions of single and multi‐spanning membrane proteins. Further, successive deletion of hydrophobic domains from the C‐terminus of the K/HDEL receptor ERD2 resulted in alternating localization of roGFP and a topology model for AtERD2 with six transmembrane domains.
MS/MS spectral tag‐based annotation of non‐targeted profile of plant secondary metabolites
Authors: Matsuda Fumio , Yonekura‐Sakakibara Keiko , Niida Rie , Kuromori Takashi , Shinozaki Kazuo , Saito Kazuki
Published: October 2008

The MS/MS spectral tag (MS2T) library‐based peak annotation procedure was developed for informative non‐targeted metabolic profiling analysis using LC‐MS. An MS2T library of Arabidopsis metabolites was created from a set of MS/MS spectra acquired using the automatic data acquisition function of the mass spectrometer. By using this library, we obtained structural information for the detected peaks in the metabolic profile data without performing additional MS/MS analysis; this was achieved by searching for the corresponding MS2T accession in the library. In the case of metabolic profile data for Arabidopsis tissues containing more than 1000 peaks, approximately 50% of the peaks were tagged by MS2Ts, and 90 peaks were identified or tentatively annotated with metabolite information by searching the metabolite databases and manually interpreting the MS2Ts. A comparison of metabolic profiles among the Arabidopsis tissues revealed that many unknown metabolites accumulated in a tissue‐specific manner, some of which were deduced to be unusual Arabidopsis metabolites based on the MS2T data. Candidate genes responsible for these biosyntheses could be predicted by projecting the results to the transcriptome data. The method was also used for metabolic phenotyping of a subset of Ds transposon‐inserted lines of Arabidopsis, resulting in clarification of the functions of reported genes involved in glycosylation of flavonoids. Thus, non‐targeted metabolic profiling analysis using MS2T annotation methods could prove to be useful for investigating novel functions of secondary metabolites in plants.
Transfusion‐related immunomodulation: a second hit in an inflammatory cascade?
Authors: Bilgin Y. M. , Brand A.
Published: October 2008

Allogeneic blood transfusions are dose‐dependently associated with postoperative complications. Leucocytes present in blood components may play a role in these effects, referred to as transfusion‐related immunomodulation. Of 19 randomized controlled trials of the effect of allogeneic leucocytes in transfusions, 13 looked into the effect of leucocyte‐containing red blood cells (RBCs) in the surgical setting on the occurrence of postoperative infections and/or mortality. In contrast to conflicting outcomes of the trials in other settings, in cardiac surgery there is evidence that leucocyte‐containing RBCs increase postoperative complications associated with mortality. The studies performed in cardiac surgery show less heterogeneity than studies in other surgical interventions and had been conducted either in one or a few participating centres. In this review, we discuss possible explanations for these results in cardiac surgery (as opposed to other settings), which may relate to clinical as well as transfusional factors. We suggest that leucocyte‐containing transfusions during and after cardiac surgery add a second insult to the cardiopulmonary bypass procedure‐induced systemic inflammatory response.