bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Echolocation: Pitch versus Loudness Information
Authors: Schenkman Bo N , Nilsson Mats E
Published: August 2011

Blind persons emit sounds to detect objects by echolocation. Both perceived pitch and perceived loudness of the emitted sound change as they fuse with the reflections from nearby objects. Blind persons generally are better than sighted at echolocation, but it is unclear whether this superiority is related to detection of pitch, loudness, or both. We measured the ability of twelve blind and twenty-five sighted listeners to determine which of two sounds, 500 ms noise bursts, that had been recorded in the presence of a reflecting object in a room with reflecting walls using an artificial head. The sound pairs were original recordings differing in both pitch and loudness, or manipulated recordings with either the pitch or the loudness information removed. Observers responded using a 2AFC method with verbal feedback. For both blind and sighted listeners the performance declined more with the pitch information removed than with the loudness information removed. In addition, the blind performed clearly better than the sighted as long as the pitch information was present, but not when it was removed. Taken together, these results show that the ability to detect pitch is a main factor underlying high performance in human echolocation.
Reproductive biology of the eastern shovelnose stingaree Trygonoptera imitata from south-eastern Australia
Authors: Trinnie Fabian I. , Walker Terence I. , Jones Paul L. , Laurenson Laurie J.
Published: August 2011

In applying a quantitative approach to the reproduction of Trygonoptera imitata, the present study contributes to understanding the wide diversity in the reproductive biology of the family Urolophidae and provides insights to help determine phylogenetic relationships. This localised species is taken as bycatch in several inshore fisheries and potentially impacted by a range of other anthropogenic pressures, including introduced species, particularly in shallow-water pupping areas. T. imitata can be characterised as a species of comparatively low matrotrophic histotrophy with an extended period of relatively large eggs in utero (5–8 months) followed by rapid growth of the embryos (4–6 months). The reproductive cycle is annual with parturition occurring during late-February–April, followed immediately by ovulation. Mean size-at-birth is ~225 mm total length and there is a ~1000% gain in mean wet mass from egg (15 g) to full-term embryo in utero (150 g), the lowest reported for any viviparous batoid. Litter size increases with maternal length, reaching a maximum of seven, and sex ratio of embryos is 1 : 1. Maximum length and estimates of the maturity–ogive parameters l50 and l95 are similar for females and males.
Heme oxygenase-1 and carbon monoxide modulate DNA repair through ataxia-telangiectasia mutated (ATM) protein
Authors: Otterbein Leo E. , Hedblom Andreas , Harris Clair , Csizmadia Eva , Gallo David , Wegiel Barbara
Published: August 2011

Stability and repair of DNA is of principal importance in cell survival. Heme oxygenase-1 (HO-1; Hmox1) is critical in maintaining cellular homeostasis, in large part through its ability to generate CO, but neither molecule has been studied in the setting of DNA damage. Naïve
Hmox1

−
/
−

mice exhibit excessive tissue levels of γ-histone H2A, whereas administration of genotoxic stressors or irradiation in HO-1–deficient cells resulted in loss of ataxia-telangiectasia mutated/ataxia telangiectasia and Rad3-related protein and breast cancer 1, early onset induction with dysfunctional γ-H2AX foci and marked elevations in DNA damage. HO-1 induction or exposure to CO induced homologous recombination-mediated DNA repair through ataxia-telangiectasia mutated/ataxia telangiectasia and Rad3-related protein. In vivo, exposure of mice to CO followed by genotoxin (Adriamycin) or radiation-induced injury led to diminished tissue DNA damage and improved survival. We characterize a joint role for HO-1 and the gasotransmitter CO for appropriate DNA repair and provide a mechanism for their potent cytoprotective effects in various pathologies.
Isoleucine 309 acts as a C
4
catalytic switch that increases ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco) carboxylation rate in
Flaveria
Authors: Whitney Spencer M. , Sharwood Robert E. , Orr Douglas , White Sarah J. , Alonso Hernan , Galmés Jeroni
Published: August 2011

Improving global yields of important agricultural crops is a complex challenge. Enhancing yield and resource use by engineering improvements to photosynthetic carbon assimilation is one potential solution. During the last 40 million years C
4
photosynthesis has evolved multiple times, enabling plants to evade the catalytic inadequacies of the CO
2
-fixing enzyme, ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco). Compared with their C
3
ancestors, C
4
plants combine a faster rubisco with a biochemical CO
2
-concentrating mechanism, enabling more efficient use of water and nitrogen and enhanced yield. Here we show the versatility of plastome manipulation in tobacco for identifying sequences in C
4
-rubisco that can be transplanted into C
3
-rubisco to improve carboxylation rate (
V
C
). Using transplastomic tobacco lines expressing native and mutated rubisco large subunits (L-subunits) from
Flaveria pringlei
(C
3
),
Flaveria floridana
(C
3
-C
4
), and
Flaveria bidentis
(C
4
), we reveal that Met-309-Ile substitutions in the L-subunit act as a catalytic switch between C
4
(
309
Ile; faster
V
C
, lower CO
2
affinity) and C
3
(
309
Met; slower
V
C
, higher CO
2
affinity) catalysis. Application of this transplastomic system permits further identification of other structural solutions selected by nature that can increase rubisco
V
C
in C
3
crops. Coengineering a catalytically faster C
3
rubisco and a CO
2
-concentrating mechanism within C
3
crop species could enhance their efficiency in resource use and yield.
Site-specific and redox-controlled S-nitrosation of thioredoxin
Authors: Barglow Katherine T. , Knutson Charles G. , Wishnok John S. , Tannenbaum Steven R. , Marletta Michael A.
Published: August 2011

Protein
S
-nitrosation on cysteine residues has emerged as an important posttranslational modification in mammalian cells. Previous studies have suggested a primary role for thioredoxin (Trx) in controlling protein
S
-nitrosation reactions. Human Trx contains five conserved Cys, including two redox-active catalytic Cys (Cys32 and Cys35) and three non-active-site Cys (Cys62, Cys69, and Cys73), all of which have been reported as targets of
S
-nitrosation. Prior reports have studied thermodynamic end points of nitrosation reactions; however, the kinetics of Trx nitrosation has not previously been investigated. Using the transnitrosation agent,
S
-nitrosoglutathione, a kinetic analysis of the selectivity and redox dependence of Trx nitrosation at physiologically relevant concentrations and times was performed, utilizing a mass spectrometry-based method for the direct analysis of the nitrosated Trx. Reduced Trx (rTrx) was nitrosated 2.7-times faster than oxidized Trx (oTrx), and rTrx was nitrosated selectively on Cys62, whereas oTrx was nitrosated only on Cys73. These sites of nitrosation were confirmed at the peptide level using a novel modification of the biotin-switch technique called the reductive switch. These results suggest separate signaling pathways for Trx-SNO under different cellular redox states.
OBSERVATIONS OF DETAILED STRUCTURE IN THE SOLAR WIND AT 1 AU WITH STEREO/HI-2
Authors: DeForest C. E. , Howard T. A. , Tappin S. J.
Published: August 2011

We present images of solar wind electron density structures at distances of 1 AU, extracted from the STEREO/HI-2 data. Collecting the images requires separating the Thomson-scattered signal from the other background/foreground sources that are 103 times brighter. Using a combination of techniques, we are able to generate calibrated imaging data of the solar wind with sensitivity of a few × 10−17
B
☉, compared to the background signal of a few × 10−13
B
☉, using only the STEREO/HI-2 Level 1 data as input. These images reveal detailed spatial structure in coronal mass ejections (CMEs) and the solar wind at projected solar distances in excess of 1 AU, at the instrumental motion-blur resolution limit of 1°–3°. CME features visible in the newly reprocessed data from 2008 December include leading-edge pileup, interior voids, filamentary structure, and rear cusps. “Quiet” solar wind features include V-shaped structures centered on the heliospheric current sheet, plasmoids, and “puffs” that correspond to the density fluctuations observed in situ. We compare many of these structures with in situ features detected near 1 AU. The reprocessed data demonstrate that it is possible to perform detailed structural analyses of heliospheric features with visible light imagery, at distances from the Sun of at least 1 AU.
The activation of ezrin–radixin–moesin proteins is regulated by netrin-1 through Src kinase and RhoA/Rho kinase activities and mediates netrin-1–induced axon outgrowth
Authors: Antoine-Bertrand Judith , Ghogha Atefeh , Luangrath Vilayphone , Bedford Fiona K. , Lamarche-Vane Nathalie
Published: August 2011

The receptor Deleted in Colorectal Cancer (DCC) mediates the attractive response of axons to the guidance cue netrin-1 during development. On netrin-1 stimulation, DCC is phosphorylated and induces the assembly of signaling complexes within the growth cone, leading to activation of cytoskeleton regulators, namely the GTPases Rac1 and Cdc42. The molecular mechanisms that link netrin-1/DCC to the actin machinery remain unclear. In this study we seek to demonstrate that the actin-binding proteins ezrin–radixin–moesin (ERM) are effectors of netrin-1/DCC signaling in embryonic cortical neurons. We show that ezrin associates with DCC in a netrin-1–dependent manner. We demonstrate that netrin-1/DCC induces ERM phosphorylation and activation and that the phosphorylation of DCC is required in that context. Moreover, Src kinases and RhoA/Rho kinase activities mediate netrin-1–induced ERM phosphorylation in neurons. We also observed that phosphorylated ERM proteins accumulate in growth cone filopodia, where they colocalize with DCC upon netrin-1 stimulation. Finally, we show that loss of ezrin expression in cortical neurons significantly decreases axon outgrowth induced by netrin-1. Together, our findings demonstrate that netrin-1 induces the formation of an activated ERM/DCC complex in growth cone filopodia, which is required for netrin-1–dependent cortical axon outgrowth.
Citron kinase controls abscission through RhoA and anillin
Authors: Gai Marta , Camera Paola , Dema Alessandro , Bianchi Federico , Berto Gaia , Scarpa Elena , Germena Giulia , Di Cunto Ferdinando
Published: August 2011

The small GTPase RhoA plays a crucial role in the different stages of cytokinesis, including contractile ring formation, cleavage furrow ingression, and midbody abscission. Citron kinase (CIT-K), a protein required for cytokinesis and conserved from insects to mammals, is currently considered a cytokinesis-specific effector of active RhoA. In agreement with previous observations, we show here that, as in Drosophila cells, CIT-K is specifically required for abscission in mammalian cells. However, in contrast with the current view, we provide evidence that CIT-K is an upstream regulator rather than a downstream effector of RhoA during late cytokinesis. In addition, we show that CIT-K is capable of physically and functionally interacting with the actin-binding protein anillin. Active RhoA and anillin are displaced from the midbody in CIT-K-depleted cells, while only anillin, but not CIT-K, is affected if RhoA is inactivated in late cytokinesis. The overexpression of CIT-K and of anillin leads to abscission delay. However, the delay produced by CIT-K overexpression can be reversed by RhoA inactivation, while the delay produced by anillin overexpression is RhoA-independent. Altogether, these results indicate that CIT-K is a crucial abscission regulator that may promote midbody stability through active RhoA and anillin.
Spatial control of Cdc42 activation determines cell width in fission yeast
Authors: Kelly Felice D. , Nurse Paul
Published: August 2011

The fission yeast Schizosaccharomyces pombe is a rod-shaped cell that grows by linear extension at the cell tips, with a nearly constant width throughout the cell cycle. This simple geometry makes it an ideal system for studying the control of cellular dimensions. In this study, we carried out a near-genome-wide screen for mutants wider than wild-type cells. We found 11 deletion mutants that were wider; seven of the deleted genes are implicated in the control of the small GTPase Cdc42, including the Cdc42 guanine nucleotide exchange factor (GEF) Scd1 and the Cdc42 GTPase-activating protein (GAP) Rga4. Deletions of rga4 and scd1 had additive effects on cell width, and the proteins localized independently of one another, with Rga4 located at the cell sides and Scd1 at the cell tips. Activated Cdc42 localization is altered in rga4Δ, scd1Δ, and scd2Δ mutants. Delocalization and ectopic retargeting experiments showed that the localizations of Rga4 and Scd1 are crucial for their roles in determining cell width. We propose that the GAP Rga4 and the GEF Scd1 establish a gradient of activated Cdc42 within the cellular tip plasma membrane, and it is this gradient that determines cell growth-zone size and normal cell width.
Robust synthetic gene network design via library-based search method
Authors: Wu Chih-Hung , Lee Hsiao-Ching , Chen Bor-Sen
Published: August 2011

Motivation: Synthetic biology aims to develop the artificial gene networks with desirable behaviors using systematic method. These networks with desired behaviors could be constructed using diverse biological parts, which may limit the development to complex synthetic gene networks. Fortunately, some well-characterized promoter libraries for engineering gene networks are widely available. Thus, a synthetic gene network can be constructed by selecting adequate promoters from promoter libraries to achieve the desired behaviors. However, the present promoter libraries cannot be directly applied to engineer a synthetic gene network. In order to efficiently select adequate promoters from promoter libraries for a synthetic gene network, promoter libraries are needed to be redefined based on the dynamic gene regulation.

Results: Based on four design specifications, a library-based search method is proposed to efficiently select the most adequate promoter set from the redefined promoter libraries by a genetic algorithm (GA) to achieve optimal reference tracking design. As the number and size of promoter libraries increase, the proposed method can play an important role in the systematic design of synthetic biology.

Contact:  g883743@alumni.nthu.edu.tw; bschen@ee.nthu.edu.tw

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Supply chaining fishery advice
Authors: Connolly P. L. , Caffrey L.
Published: August 2011

Connolly, P. L., and Caffrey, L. 2011. Supply chaining fishery advice. – ICES Journal of Marine Science, 68: 1706–1711. The supply chain concept helps underpin global commerce. In the fishery data arena, it is an underutilized tool that could benefit the business of fishery advice. Supply chain networks can lower operating costs and increase product availability, agility, and customer satisfaction. The EU's Data Collection Framework has consolidated and strengthened data collection in Europe, but inadequate data management undermines many stock assessments of fish through the lack of supply chaining. Commercial supply chain know-how, when implemented on solid enterprise architectures, can endow fishery advice with industrial-strength scrutiny, making it transparent, standardized, integrated, agile, consistent, accurate, and timely.
Insights into mucosal innate responses to
Escherichia coli
O157 : H7 colonization of cattle by mathematical modelling of excretion dynamics
Authors: Tildesley Michael J. , Gally David L. , McNeilly Tom N. , Low J. Chris , Mahajan Arvind , Savill Nicholas J.
Published: August 2011

Mathematical model-based statistical inference applied to within-host dynamics of infectious diseases can help dissect complex interactions between hosts and microbes. This work has applied advances in model-based inference to understand colonization of cattle by enterohaemorrhagic
Escherichia coli
O157 : H7 at the terminal rectum. A mathematical model was developed based on niche replication and transition rates at this site. A nested-model comparison, applied to excretion curves from 25 calves, was used to reduce complexity while maintaining integrity. We conclude that, 5–9 days post inoculation, the innate immune response negates bacterial replication on the epithelium and either reduces attachment to or increases detachment from the epithelium of the terminal rectum. Thus, we provide a broadly applicable model that gives novel insights into bacterial replication rates
in vivo
and the timing and impact of host responses.
An equilibrium for phenotypic variance in fluctuating environments owing to epigenetics
Authors: Carja Oana , Feldman Marcus W.
Published: August 2011

The connection between random environments and genetic and phenotypic variability has been a major focus in the population genetic literature. By providing differential access to the underlying genetic information, epigenetic variation could play an important role in the interaction between environmental and phenotypic variation. Using simulation, we model epigenetic plasticity during development by investigating the dynamics of genetic regulators of the epigenetic machinery that change the variance of the phenotype, while having no effect on the phenotype's mean. Previous studies have found that increased phenotypic variance is selected for if the environment is fluctuating. Here, we find that when a variance-increasing allele achieves a sufficiently high frequency, it can be out-competed by a variance-reducing allele, with the consequence that the population evolves to an equilibrium phenotypic variability. This equilibrium is shown to be robust to different initial conditions, but to depend heavily on parameters of the model, such as the mutation rate, the fitness landscape and the nature of the environmental fluctuation. Indeed, if there is no mutation at the genes controlling the variance of the phenotype, reduction of this variance is favoured.
Computability, Gödel's incompleteness theorem, and an inherent limit on the predictability of evolution
Authors: Day Troy
Published: August 2011

The process of evolutionary diversification unfolds in a vast genotypic space of potential outcomes. During the past century, there have been remarkable advances in the development of theory for this diversification, and the theory's success rests, in part, on the scope of its applicability. A great deal of this theory focuses on a relatively small subset of the space of potential genotypes, chosen largely based on historical or contemporary patterns, and then predicts the evolutionary dynamics within this pre-defined set. To what extent can such an approach be pushed to a broader perspective that accounts for the potential open-endedness of evolutionary diversification? There have been a number of significant theoretical developments along these lines but the question of how far such theory can be pushed has not been addressed. Here a theorem is proven demonstrating that, because of the digital nature of inheritance, there are inherent limits on the kinds of questions that can be answered using such an approach. In particular, even in extremely simple evolutionary systems, a complete theory accounting for the potential open-endedness of evolution is unattainable unless evolution is progressive. The theorem is closely related to Gödel's incompleteness theorem, and to the halting problem from computability theory.
Outbreak of swine influenza in Argentina reveals a non-contemporary human H3N2 virus highly transmissible among pigs
Authors: Cappuccio Javier A. , Pena Lindomar , Dibárbora Marina , Rimondi Agustina , Piñeyro Pablo , Insarralde Lucas , Quiroga María A. , Machuca Mariana , Craig Maria I. , Olivera Valeria , Chockalingam Ashok , Perfumo Carlos J. , Perez Daniel R. , Pereda Ariel
Published: August 2011

Sporadic outbreaks of human H3N2 influenza A virus (IAV) infections in swine populations have been reported in Asia, Europe and North America since 1970. In South America, serological surveys in pigs indicate that IAVs of the H3 and H1 subtypes are currently in circulation; however, neither virus isolation nor characterization has been reported. In November 2008, an outbreak of respiratory disease in pigs consistent with swine influenza virus (SIV) infection was detected in Argentina. The current study describes the clinical epidemiology, pathology, and molecular and biological characteristics of the virus. Phylogenetic analysis revealed that the virus isolate shared nucleotide identities of 96–98 % with H3N2 IAVs that circulated in humans from 2000 to 2003. Antigenically, sera from experimentally inoculated animals cross-reacted mainly with non-contemporary human-origin H3N2 influenza viruses. In an experimental infection in a commercial swine breed, the virus was of low virulence but was transmitted efficiently to contact pigs and caused severe disease when an infected animal acquired a secondary bacterial infection. This is the first report of a wholly human H3N2 IAV associated with clinical disease in pigs in South America. These studies highlight the importance of two-way transmission of IAVs and SIVs between pigs and humans, and call for enhanced influenza surveillance in the pig population worldwide.
LRH-1 and PTF1-L coregulate an exocrine pancreas-specific transcriptional network for digestive function
Authors: Holmstrom Sam R. , Deering Tye , Swift Galvin H. , Poelwijk Frank J. , Mangelsdorf David J. , Kliewer Steven A. , MacDonald Raymond J.
Published: August 2011

We have determined the cistrome and transcriptome for the nuclear receptor liver receptor homolog-1 (LRH-1) in exocrine pancreas. Chromatin immunoprecipitation (ChIP)-seq and RNA-seq analyses reveal that LRH-1 directly induces expression of genes encoding digestive enzymes and secretory and mitochondrial proteins. LRH-1 cooperates with the pancreas transcription factor 1-L complex (PTF1-L) in regulating exocrine pancreas-specific gene expression. Elimination of LRH-1 in adult mice reduced the concentration of several lipases and proteases in pancreatic fluid and impaired pancreatic fluid secretion in response to cholecystokinin. Thus, LRH-1 is a key regulator of the exocrine pancreas-specific transcriptional network required for the production and secretion of pancreatic fluid.
miR than meets the eye: Figure 1.
Authors: Sage Julien , Ventura Andrea
Published: August 2011

Retinoblastoma is a rare pediatric cancer that has served as a paradigm to investigate the mechanisms of tumorigenesis. In this issue of Genes & Development, Conkrite and colleagues (pp. 1734–1745) found high levels of the miR-17∼92 and miR-106b-25 microRNAs in primary retinoblastomas and show that overexpression of miR-17∼92 accelerates retinoblastoma development in mice by promoting proliferation, in part by reducing expression of the cell cycle inhibitor p21. These experiments identify the RB/miR-17∼92/p21 axis as a critical regulator of retinoblastoma tumorigenesis and potentially many other cancers.
Effect of prison‐based opioid substitution treatment and post‐release retention in treatment on risk of re‐incarceration
Authors: Larney Sarah , Toson Barbara , Burns Lucy , Dolan Kate
Published: August 2011

Aims  People who use heroin are frequently incarcerated multiple times. Reducing re‐incarceration of this group is important for reducing both health risks associated with incarceration and the costs of correctional administration. Opioid substitution treatment (OST) in prisons may help to reduce re‐incarceration, but research findings on this topic have been mixed. In this study, we examined the effect of OST in prison and after release on re‐incarceration.

Design  Longitudinal cohort study.

Setting, participants and measurements  Data on OST and incarceration were linked for a cohort of 375 male heroin users recruited originally in prisons in New South Wales, Australia. Data were linked for the period 1 June 1997–31 December 2006. Re‐incarceration was examined using recurrent‐event survival analysis models. Model 1 examined the effect of OST status at release from prison (i.e. in treatment versus out of treatment on the day of release) on re‐incarceration. Model 2 considered the effect of remaining in OST after release on risk of re‐incarceration.

Findings  Ninety per cent of participants were re‐incarcerated following their first observed release. Pre‐incarceration cocaine use was associated with a 13% increase in the average risk of re‐incarceration. There was no significant association between simply being in OST at the time of release and risk of re‐incarceration; however, in the model taking into account post‐release retention in treatment, the average risk of re‐incarceration was reduced by 20% while participants were in treatment.

Conclusions  In New South Wales, Australia, opioid substitution treatment after release from prison has reduced the average risk of re‐incarceration by one‐fifth.
Assessment of the cardiac safety of prucalopride in healthy volunteers: a randomized, double‐blind, placebo‐ and positive‐controlled thorough QT study
Authors: Mendzelevski Boaz , Ausma Jannie , Chanter Dennis O. , Robinson Patricia , Kerstens Rene , Vandeplassche Lieve , Camm John
Published: August 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Drugs interacting with the hERG potassium channel are associated with a prolongation of the QT interval, which can lead to life‐threatening arrhythmias such as torsades de pointes.

• Early prokinetic agents, such as cisapride, display poor selectivity for their target receptor, 5‐HT4, also interacting with hERG channels and, as a consequence, have a poor safety and benefit/risk profile.

• Prucalopride, a novel and selective 5‐HT4 agonist with enterokinetic activity, is indicated for the treatment of chronic constipation in adults in whom laxatives fail to provide adequate relief.

WHAT THIS STUDY ADDS

• This study describes the results of a novel thorough QT study design involving a parallel group with nested crossover for positive control.

• The mean QTc interval was not prolonged in patients receiving therapeutic (2 mg) or supra‐therapeutic (10 mg) doses of prucalopride, as assessed using QTcSS.

• New generation prokinetic agents with improved selectivity for 5‐HT4 receptors, such as prucalopride, should help improve the benefit/risk profile of these agents and, ultimately, their clinical usefulness.

AIMS To assess steady‐state effects of therapeutic and supra‐therapeutic doses of prucalopride on the QT interval using a novel design involving a parallel placebo group with nested crossover for positive control.

METHODS A double‐blind, double‐dummy, placebo‐ and active‐controlled study was conducted in 120 healthy male and female volunteers (NCT00903747). Volunteers were randomized to receive prucalopride 2–10 mg once daily (therapeutic and supratherapeutic doses, respectively) (group 1), placebo with 400 mg moxifloxacin on day 1 (group 2a), or placebo with moxifloxacin on day 15 (group 2b). Twelve‐lead 24 h Holter ECGs recorded at various time‐points were evaluated blind and centrally.

RESULTS Estimated mean difference in study specific corrected QT interval (QTcSS) time‐matched change from baseline between prucalopride (2 and 10 mg) and placebo was <5 ms at all time points (maximum mean difference: 3.83 ms at 3.5 h post dose on day 5 with 2 mg [90% Cl −0.33, 6.38 ms]). Upper limits of the two‐sided 90% CI for QTcSS were all <10 ms. There were no outlying QTcSS values >450 ms and no subjects had an increase >60 ms following prucalopride. Moxifloxacin produced the expected significant changes in QTcSS (>5 ms, maximum of +12.7 ms at 5 h post dose) at all time‐points except 1 h post dose. Prucalopride resulted in small increases in heart rate (maximum of 5.8 beats min–1), which were similar for 2 and 10 mg. Prucalopride was well tolerated after first day of treatment.

CONCLUSION Prucalopride at both therapeutic and supra therapeutic doses has no clinically significant effects on cardiac repolarisation in healthy volunteers.
Constitutional trisomy 8p11.21‐q11.21 mosaicism: a germline alteration predisposing to myeloid leukaemia
Authors: Ripperger Tim , Tauscher Marcel , Praulich Inka , Pabst Brigitte , Teigler‐Schlegel Andrea , Yeoh Allen , Göhring Gudrun , Schlegelberger Brigitte , Flotho Christian , Niemeyer Charlotte M. , Steinemann Doris
Published: August 2011

Juvenile myelomonocytic leukaemia (JMML) is a unique myeloproliferative disorder of early childhood. Frequently, mutations in NRAS, KRAS, PTPN11, NF1 or CBL are found in these patients. Monosomy 7 is the most common cytogenetic aberration. To identify submicroscopic genomic copy number alterations, 20 JMML samples were analysed by comparative genomic hybridization. Ten out of 20 samples displayed additional submicroscopic alterations. In two patients, an almost identical gain of chromosome 8 was identified. In both patients, fluorescence in situ hybridization confirmed a constitutional partial trisomy 8 mosaic (cT8M). A survey on 27 cT8M patients with neoplasms showed that 21 had myeloid malignancies, and five of these had a JMML. Notably, the region gained in our cases is the smallest gain of chromosome 8 reported in cT8M cases with malignancies so far. Our results dramatically reduce the critical region to 8p11.21q11.21 harbouring 31 protein coding genes and two non‐coding RNAs, e.g. MYST3, IKBKB, UBE2V2, GOLGA7, FNTA and MIR486– a finding with potential implications for the role of somatic trisomy 8 in myeloid malignancies. Further investigations are required to more comprehensively determine how constitutional partial trisomy 8 mosaicisms may contribute to leukaemogenesis in different mutational subtypes of JMML and other myeloid malignancies.
Proinflammatory and regulatory cytokines and chemokines in infants with uncomplicated and severePlasmodium falciparummalaria
Authors: Ayimba E , Hegewald J , Ségbéna A Y , Gantin R G , Lechner C J , Agosssou A , Banla M , Soboslay P T
Published: August 2011

Cytokine and chemokine levels were studied in infants (<5 years) with uncomplicated (MM) and severe malaria tropica (SM), and in Plasmodium falciparum infection-free controls (NEG). Cytokine plasma levels of interleukin (IL)-10, IL-13, IL-31 and IL-33 were strongly elevated in MM and SM compared to NEG (P < 0·0001). Inversely, plasma concentrations of IL-27 were highest in NEG infants, lower in MM cases and lowest in those with SM (P < 0·0001, NEG compared to MM and SM). The levels of the chemokines macrophage inflammatory protein (MIP3)-α/C–C ligand 20 (CCL20), monokine induced by gamma interferon (MIG)/CXCL9 and CXCL16 were enhanced in those with MM and SM (P < 0·0001 compared to NEG), and MIP3-α/CCL20 and MIG/CXCL9 were correlated positively with parasite density, while that of IL-27 were correlated negatively. The levels of 6Ckine/CCL21 were similar in NEG, MM and SM. At 48–60 h post-anti-malaria treatment, the plasma concentrations of IL-10, IL-13, MIG/CXCL9, CXCL16 and MIP3-α/CCL20 were clearly diminished compared to before treatment, while IL-17F, IL-27, IL-31 and IL-33 remained unchanged. In summary, elevated levels of proinflammatory and regulatory cytokines and chemokines were generated in infants during and after acute malaria tropica. The proinflammatory type cytokines IL-31 and IL-33 were enhanced strongly while regulatory IL-27 was diminished in those with severe malaria. Similarly, MIP3-α/CCL20 and CXCL16, which may promote leucocyte migration into brain parenchyma, displayed increased levels, while CCL21, which mediates immune surveillance in central nervous system tissues, remained unchanged. The observed cytokine and chemokine production profiles and their dynamics may prove useful in evaluating either the progression or the regression of malarial disease.
Roles for Oestrogen Receptor β in Adult Brain Function
Authors: Handa R. J. , Ogawa S. , Wang J. M. , Herbison A. E.
Published: August 2011

Oestradiol exerts a profound influence upon multiple brain circuits. For the most part, these effects are mediated by oestrogen receptor (ER)α. We review here the roles of ERβ, the other ER isoform, in mediating rodent oestradiol‐regulated anxiety, aggressive and sexual behaviours, the control of gonadotrophin secretion, and adult neurogenesis. Evidence exists for: (i) ERβ located in the paraventricular nucleus underpinning the suppressive influence of oestradiol on the stress axis and anxiety‐like behaviour; (ii) ERβ expressed in gonadotrophin‐releasing hormone neurones contributing to oestrogen negative‐feedback control of gonadotrophin secretion; (iii) ERβ controlling the offset of lordosis behaviour; (iv) ERβ suppressing aggressive behaviour in males; (v) ERβ modulating responses to social stimuli; and (vi) ERβ in controlling adult neurogenesis. This review highlights two major themes; first, ERβ and ERα are usually tightly inter‐related in the oestradiol‐dependent control of a particular brain function. For example, even though oestradiol feedback to control reproduction occurs principally through ERα‐dependent mechanisms, modulatory roles for ERβ also exist. Second, the roles of ERα and ERβ within a particular neural network may be synergistic or antagonistic. Examples of the latter include the role of ERα to enhance, and ERβ to suppress, anxiety‐like and aggressive behaviours. Splice variants such as ERβ2, acting as dominant negative receptors, are of further particular interest because their expression levels may reflect preceeding oestradiol exposure of relevance to oestradiol replacement therapy. Together, this review highlights the predominant modulatory, but nonetheless important, roles of ERβ in mediating the many effects of oestradiol upon adult brain function.
Effect of treatment with fixed and removable dental prostheses. An oral health‐related quality of life study
Authors: ÖZHAYAT E. B. , GOTFREDSEN K.
Published: August 2011

Summary  The aim of the study was to evaluate patient‐reported effects of treatment with fixed dental prostheses (FDP) and removable dental prostheses (RDP) and relate the change in Oral Health Related Quality of Life (OHRQoL) to the type of treatment and objective dental variables of aesthetics and mastication. Additionally, the purpose of the study was to identify aspects of impairment and improvement that the treatments caused. Fixed dental prostheses treatment was performed in 200 patients and RDP treatment in 107 patients. Gender, age, region of replacement, and number of teeth present and replaced were obtained. The participants completed the Oral Health Impact Profile 49 (OHIP‐49) before and after treatment. A control group with no need for dental treatment also completed the OHIP‐49. All participants had a significant improvement in OHRQoL. The improvement was higher for the RDP group than the FDP group. Removable dental prostheses that replaced only masticatory teeth did not improve the OHRQoL significantly. The improvement in OHRQoL for both the FDP and RDP groups was not at the level of the control group. Higher age was associated with lower improvement in OHRQoL. Higher age, being a woman and having teeth replaced in the aesthetic zone were associated with deterioration in OHRQoL. Both RDP treatment and FDP treatment were associated with a reduction in the problems most frequently reported before treatment. Treatment with RDP was associated with new problems caused by the RDP. Fixed dental prostheses and RDP treatments improved OHRQoL and reduced the number of problems. The RDP participants improved more than the FDP participants.
Age effects on spectral electroencephalogram activity prior to dream recall
Authors: CHELLAPPA SARAH L. , MÜNCH MIRJAM , KNOBLAUCH VERA , CAJOCHEN CHRISTIAN
Published: August 2011

Ageing is associated with marked changes in sleep timing, structure and electroencephalographic (EEG) activity. Older people exhibit less slow‐wave and spindle activity during non‐rapid eye movement (NREM) sleep, together with attenuated levels of rapid eye movement (REM) sleep as compared to young individuals. However, the extent to which these age‐related changes in sleep impact on dream processing remains largely unknown. Here we investigated NREM and REM sleep EEG activity prior to dream recall and no recall in 17 young (20–31 years) and 15 older volunteers (57–74 years) during a 40 h multiple nap protocol. Dream recall was assessed immediately after each nap. During NREM sleep prior to dream recall, older participants displayed higher frontal EEG delta activity (1–3 Hz) and higher centro‐parietal sigma activity (12–15 Hz) than the young volunteers. Conversely, before no recall, older participants had less frontal‐central delta activity and less sigma activity in frontal, central and parietal derivations than the young participants. REM sleep was associated to age‐related changes, such that older participants had less frontal‐central alpha (10–12 Hz) and beta (16–19 Hz) activity, irrespective of dream recall and no recall. Our data indicate that age‐related differences in dream recall seem to be directly coupled to specific frequency and topography EEG patterns, particularly during NREM sleep. Thus, the spectral correlates of dreaming can help to understand the cortical pathways of dreaming.
Phylogeographic heterogeneity of the brown macroalgaSargassum horneri(Fucaceae) in the northwestern Pacific in relation to late Pleistocene glaciation and tectonic configurations
Authors: HU ZI‐MIN , UWAI SHINYA , YU SHEN‐HUI , KOMATSU TERUHISA , AJISAKA TETSURO , DUAN DE‐LIN
Published: August 2011

Pleistocene glacial oscillations and associated tectonic processes are believed to have influenced the historical abundances and distribution of organisms in the Asia Northwest Pacific (ANP). Accumulating evidence indicates that factors shaping tempospatial population dynamics and distribution patterns of marine taxa vary with biogeographical latitude, pelagic behaviour and oceanographic regimes. To detect what kinds of historical and contemporary factors affected genetic connectivity, phylogeographic profiles of littoral macroalgaSargassum horneriin the ANP were analysed based on mitochondrial (Cox3) and chloroplast (rbcL) data sets. Five distinct clades were recovered. A strong signature of biogeographical structure was revealed (ΦCT = 0.487,P < 0.0001) derived from remarkable differentiation in clade distribution, as clade I is restricted to Chinese marginal seas (Yellow–Bohai Sea, East China Sea and South China Sea), whereas clades II–V are discontinuously scattered around the main Islands of Japan. Furthermore, two secondary contact regions were identified along the south Japan‐Pacific coastline. This significant differentiation between the two basins may reflect historical glacial isolation in the northwestern Pacific, which is congruent with the estimates of clade divergence and demographic expansion during the late Quaternary low sea levels. Analysis of molecular variance and the population‐pair statisticFSTalso revealed significant genetic structural differences between Chinese marginal seas and the Japanese basin. This exceptional phylogeographic architecture inS. horneri, initially shaped by historical geographic isolation during the late Pleistocene ice age and physical biogeographical barriers, can be complicated by oceanographic regimes (ocean surface currents) and relocating behaviour such as oceanic drifting.
Polymorphisms of innate immunity receptors in infection by parasites
Authors: VILLASEÑOR‐CARDOSO M. I. , ORTEGA E.
Published: August 2011

The innate immune system is the first line of defence against infection by pathogenic bacteria, virus and parasites and is also responsible for initiating an adaptive immune response. In contrast to the receptors of adaptive immunity (TCRs and antibodies) which are generated by gene recombination, receptors of the innate immune system are encoded in the germline and are thus inherited from generation to generation. Although evolutionarily selected, the genes encoding the innate recognition receptors show variations among individuals, and these polymorphisms may have an impact on the ability of an individual to deal with an infection. In recent years, several polymorphisms have been identified in innate recognition receptors, and efforts are being made to determine whether these polymorphisms are associated with a higher or lower susceptibility to infectious diseases. These studies will allow a better understanding of the role of innate receptors in specific diseases and are valuable in the design of preventive or therapeutic interventions to fight the disease. In this review, we summarize studies aimed at determining the influence of polymorphisms in innate recognition receptors on the susceptibility to diseases caused by parasites.
Sequence divergence and loss‐of‐function phenotypes of S locus F‐box brothers genes are consistent with non‐self recognition by multiple pollen determinants in self‐incompatibility of Japanese pear (Pyrus pyrifolia)
Authors: Kakui Hiroyuki , Kato Masaki , Ushijima Koichiro , Kitaguchi Miyoko , Kato Shu , Sassa Hidenori
Published: August 2011

The S‐RNase‐based gametophytic self‐incompatibility (SI) of Rosaceae, Solanaceae, and Plantaginaceae is controlled by at least two tightly linked genes located at the complex S locus; the highly polymorphic S‐RNase for pistil specificity and the F‐box gene (SFB/SLF) for pollen. Self‐incompatibility in Prunus (Rosaceae) is considered to represent a ‘self recognition by a single factor’ system, because loss‐of‐function of SFB is associated with self‐compatibility, and allelic divergence of SFB is high and comparable to that of S‐RNase. In contrast, Petunia (Solanaceae) exhibits ‘non‐self recognition by multiple factors’. However, the distribution of ‘self recognition’ and ‘non‐self recognition’ SI systems in different taxa is not clear. In addition, in ‘non‐self recognition’ systems, a loss‐of‐function phenotype of pollen S is unknown. Here we analyze the divergence of SFBB genes, the multiple pollen S candidates, of a rosaceous plant Japanese pear (Pyrus pyrifolia) and show that intrahaplotypic divergence is high and comparable to the allelic diversity of S‐RNase while interhaplotypic divergence is very low. Next, we analyzed loss‐of‐function of the SFBB1 type gene. Genetic analysis showed that pollen with the mutant haplotype S4sm lacking SFBB1‐S4 is rejected by pistils with an otherwise compatible S1 while it is accepted by other non‐self pistils. We found that the S5 haplotype encodes a truncated SFBB1 protein, even though S5 pollen is accepted normally by pistils with S1 and other non‐self haplotypes. These findings suggest that Japanese pear has a ‘non‐self recognition by multiple factors’ SI system, although it is a species of Rosaceae to which Prunus also belongs.
Gal/non‐Gal antigens in pig tissues and human non‐Gal antibodies in the GalT‐KO era1
Authors: Breimer Michael E.
Published: August 2011

Breimer ME. Gal/non‐Gal antigens in pig tissues and human non‐Gal antibodies in the GalT‐KO era. Xenotransplantation 2011; 18: 215–228. © 2011 John Wiley & Sons A/S.

Abstract:  Our knowledge regarding Gal and non‐Gal antigens in GalT‐KO pig tissues can be summarized as α3Galactosyl‐tranferase gene knock out eliminates the Galα3Galβ4GlcNAc‐R antigen expression in pig tissues as well as anti‐Gal antibody binding. Other Galα‐terminating saccharides (e.g. iGb3 glycolipids and Galα2 determinants) may be present but have not been documented. α3Galactosyl‐tranferase gene knock out slightly changes the carbohydrate antigen expression but no “new” antigens recognized by the human immune system have been found. Non‐Gal antigens are both of protein and carbohydrate nature but their exact chemical structures are poorly defined. Regarding human non‐Gal antibodies our knowledge is as Non‐Gal antibodies exist naturally and increase in humans/non‐human primate (NHP) receiving WT or GalT‐KO pig grafts. Non‐Gal antibodies with new antigen epitope recognition can be induced in humans/NHP after challenge by WT or GalT‐KO pig grafts. Non‐Gal antibodies react with both carbohydrates and proteins. Part of the protein reactivity is directed to glycoprotein carbohydrates chains. Non‐Gal antibodies reacting with neuraminic acid terminated saccharides (both N‐Acetyl and N‐Glycoloyl variants) are present in humans/NHP. Anti‐neuraminic acid antibodies are increased, as well as induced, after grafting pig organs into humans/NHP. Non‐Gal antibodies does not cause hyperacute xenorejection but can be cytotoxic and cause xenoorgan damage. If humans sensitized to HLA antigens are at a higher risk of rejecting pig xenograft compared with non‐sensitized individuals is not fully clarified.

Clinical trials are needed to evaluate the relevance of non‐Gal antigens/antibodies and for the xenofield to advance.
A Suitable Duplex PCR for Ovine Embryo Sex and Genotype of PrnP Gene Determination for MOET‐Based Selection Programmes
Authors: Dervishi E , Sánchez P , Alabart JL , Cocero MJ , Folch J , Calvo JH
Published: August 2011

Contents

The objective of this study was to test the suitability of a duplex PCR assay for sex and scrapie resistance genotype determination in fresh embryos. Duplex PCR amplified a repetitive and specific fragment of Y chromosome, used for sex diagnosis, and a PrnP fragment. PrnP codons 134 and 156, and codon 171 were genotyped by restriction fragment length polymorphisms and allele‐specific PCR, respectively, after re‐amplification of PrnP fragment. The specificity of the method was first assessed by testing 359 blood samples from Rasa Aragonesa sheep breed (161 males and 198 females). No amplification failures and total agreement between genotypic and phenotypic sex were found. In the same way, PrnP genotype determination by duplex PCR assay was in agreement with the PrnP animal’s genotype established by sequencing. Finally, 73 samples of 1–10 cells from compact morulae were aspirated through the zona pellucida and genotyped for sex and PrnP. The efficiency was 96% when three or more cells were sampled. These results confirm that the duplex PCR assay reported in this work can be used for rapid sex determination in ovine embryos, with a high efficiency and accuracy (96%) when three or more cells are sampled, allowing sexed fresh embryos of known PrnP genotype to be transferred in multiple ovulation and embryo transfer programmes.