bluuebunny/crossref_metadata_2025 huggingface dataset:
Richard Darwin Keynes CBE. 14 August 1919 — 12 June 2010
Authors: Glynn Ian
Published: May 2011

From the time that Richard Keynes became a research student in 1946, until well after he retired in 1986, a main aim of his work was to get a better understanding of the machinery in nerve cells that was responsible for the changes in the fluxes of sodium and potassium ions that Alan Hodgkin and Andrew Huxley had shown give rise to ‘action potentials’—the transient ‘all-or-nothing’ alterations in transmembrane voltage that are the sole constituent of messages transmitted along nerve fibres. In the later part of his life he also contributed significantly to our knowledge of Charles Darwin, his own great-grandfather.
Modelling platelet–blood flow interaction using the subcellular element Langevin method
Authors: Sweet Christopher R. , Chatterjee Santanu , Xu Zhiliang , Bisordi Katharine , Rosen Elliot D. , Alber Mark
Published: May 2011

In this paper, a new three-dimensional modelling approach is described for studying fluid–viscoelastic cell interaction, the subcellular element Langevin (SCEL) method, with cells modelled by subcellular elements (SCEs) and SCE cells coupled with fluid flow and substrate models by using the Langevin equation. It is demonstrated that: (i) the new method is computationally efficient, scaling as 𝒪(
N
) for
N
SCEs; (ii) cell geometry, stiffness and adhesivity can be modelled by directly relating parameters to experimentally measured values; (iii) modelling the fluid–platelet interface as a surface leads to a very good correlation with experimentally observed platelet flow interactions. Using this method, the three-dimensional motion of a viscoelastic platelet in a shear blood flow was simulated and compared with experiments on tracking platelets in a blood chamber. It is shown that the complex platelet-flipping dynamics under linear shear flows can be accurately recovered with the SCEL model when compared with the experiments. All experimental details and electronic supplementary material are archived at http://biomath.math.nd.edu/scelsupplementaryinformation/.
Transmission coefficients for the exact triangular barrier: an exact general analytical theory that can replace Fowler & Nordheim's 1928 theory
Authors: Forbes Richard G. , Deane Jonathan H. B.
Published: May 2011

In field electron emission theory, evaluating the transmission coefficient
D
ET
for an exact triangular (ET) potential energy barrier is a paradigm problem. This paper derives a compact, exact, general analytical expression for
D
ET
, by means of an Airy function approach that uses a reflected barrier and puts the origin of coordinates at the electron's outer classical turning point. This approach has simpler mathematics than previous treatments. The expression derived applies to both tunnelling and ‘flyover’ (wave-mechanical transmission over the barrier), and is easily evaluated by computer algebra. The outcome is a unified theory of transmission across the ET barrier. In different ranges of relevant physical parameters, the expression yields different approximate formulae. For some ranges, no simple physical dependences exist. Ranges of validity for the most relevant formulae (including the Fowler–Nordheim 1928 formula for
D
ET
) are explored, and a regime diagram constructed. Previous treatments are assessed and some discrepancies noted. Further approximations involved in deriving the Fowler–Nordheim 1928 equation for current density are stated. To assist testing of numerical procedures, benchmark values of
D
ET
are stated to six significant figures. This work may be helpful background for research into transmission across barriers for which no exact analytical theory yet exists.
Diffusion-controlled growth of pearlite in ternary steels
Authors: Pandit A. S. , Bhadeshia H. K. D. H.
Published: May 2011

A theory for the diffusion-controlled growth of pearlite in steels containing manganese is presented and assessed in the light of experimental data. Given the overwhelmingly rapid diffusivity that a substitutional solute has within the transformation front, the growth rate is found to be dominated by diffusion parallel to the interface with austenite as the rate controlling step. The relevant interfacial diffusion parameters have been derived by fitting experimental data to kinetic theory. All reported measurements of pearlite growth where the full set of necessary parameters have been listed, are shown to be inconsistent with mechanisms that do not involve the partitioning of substitutional solutes. The method adopted here, which is based on the local equilibrium at the transformation interface with the long-range partitioning of substitutional solutes by migration within the interface, has been shown to reasonably explain experimental data over a range of temperatures and chemical compositions.
Developmental modularity and phenotypic novelty within a biphasic life cycle: morphogenesis of a cone snail venom gland
Authors: Page Louise R.
Published: May 2011

The venom gland of predatory cone snails (
Conus
spp.), which secretes neurotoxic peptides that rapidly immobilize prey, is a proposed key innovation for facilitating the extraordinary feeding behaviour of these gastropod molluscs. Nevertheless, the unusual morphology of this gland has generated controversy about its evolutionary origin and possible homologues in other gastropods. I cultured feeding larvae of
Conus lividus
and cut serial histological sections through the developing foregut during larval and metamorphic stages to examine the development of the venom gland. Results support the hypothesis of homology between the venom gland and the mid-oesophageal gland of other gastropods. They also suggest that the mid-region of the gastropod foregut, like the anterior region, is divisible into dorsal and ventral developmental modules that have different morphological, functional and ontogenetic fates. In larvae of
C. lividus
, the ventral module of the middle foregut transformed into the anatomically novel venom gland of the post-metamorphic stage by rapidly pinching-off from the main dorsal channel of the mid-oesophagus, an epithelial remodelling process that may be similar to other cases where epithelial tubes and vesicles arise from a pre-existing epithelial sheet. The developmental remodelling mechanism could have facilitated an abrupt evolutionary transition to the derived morphology of this important gastropod feeding innovation.
Unique genetic variation at a species' rear edge is under threat from global climate change
Authors: Provan Jim , Maggs Christine A.
Published: May 2011

Global climate change is having a significant effect on the distributions of a wide variety of species, causing both range shifts and population extinctions. To date, however, no consensus has emerged on how these processes will affect the range-wide genetic diversity of impacted species. It has been suggested that species that recolonized from low-latitude refugia might harbour high levels of genetic variation in rear-edge populations, and that loss of these populations could cause a disproportionately large reduction in overall genetic diversity in such taxa. In the present study, we have examined the distribution of genetic diversity across the range of the seaweedChondrus crispus, a species that has exhibited a northward shift in its southern limit in Europe over the last 40 years. Analysis of 19 populations from both sides of the North Atlantic using mitochondrial single nucleotide polymorphisms (SNPs), sequence data from two single-copy nuclear regions and allelic variation at eight microsatellite loci revealed unique genetic variation for all marker classes in the rear-edge populations in Iberia, but not in the rear-edge populations in North America. Palaeodistribution modelling and statistical testing of alternative phylogeographic scenarios indicate that the unique genetic diversity in Iberian populations is a result not only of persistence in the region during the last glacial maximum, but also because this refugium did not contribute substantially to the recolonization of Europe after the retreat of the ice. Consequently, loss of these rear-edge populations as a result of ongoing climate change will have a major effect on the overall genetic diversity of the species, particularly in Europe, and this could compromise the adaptive potential of the species as a whole in the face of future global warming.
Scaling-up anti-predator phenotypic responses of prey: impacts over multiple generations in a complex aquatic community
Authors: Peacor Scott D. , Pangle Kevin L. , Schiesari Luis , Werner Earl E.
Published: May 2011

Non-consumptive effects (NCEs) of predators owing to induced changes in prey traits are predicted to influence the structure of ecological communities. However, evidence of the importance of NCEs is limited primarily to simple systems (e.g. two to four species) over relatively short periods (e.g. less than one generation). We examined the NCEs of a fish predator, arising from phenotypic plasticity in zooplankton prey traits, over multiple generations of a diverse zooplankton community. The presence of fish, caged to remove consumptive effects, strongly influenced zooplankton community structure, through both direct and indirect NCE pathways, altering the abundance of many taxa by magnitudes as large as 3 to 10-fold. Presence of fish affected different species of cladocerans and copepods both positively and negatively. A particularly striking result was the reversal of dominance in copepod taxa: presence of fish reduced the ratio of calanoids to cyclopoids from 6.3 to 0.43. Further, the NCE of fish had a strong negative trophic cascade to zooplankton resources (phytoplankton). To our knowledge, this is the first experiment to show that NCEs can influence the abundance of multiple prey species over time spans of multiple prey generations. Our findings demonstrate that adaptive phenotypic plasticity of individuals can scale-up to affect the structure of ecological communities.
The Cytosolic/Nuclear HSC70 and HSP90 Molecular Chaperones Are Important for Stomatal Closure and Modulate Abscisic Acid-Dependent Physiological Responses in Arabidopsis
Authors: Clément Mathilde , Leonhardt Nathalie , Droillard Marie-Jo , Reiter Ilja , Montillet Jean-Luc , Genty Bernard , Laurière Christiane , Nussaume Laurent , Noël Laurent D.
Published: May 2011

Cytosolic/nuclear molecular chaperones of the heat shock protein families HSP90 and HSC70 are conserved and essential proteins in eukaryotes. These proteins have essentially been implicated in the innate immunity and abiotic stress tolerance in higher plants. Here, we demonstrate that both chaperones are recruited in Arabidopsis (Arabidopsis thaliana) for stomatal closure induced by several environmental signals. Plants overexpressing HSC70-1 or with reduced HSP90.2 activity are compromised in the dark-, CO2-, flagellin 22 peptide-, and abscisic acid (ABA)-induced stomatal closure. HSC70-1 and HSP90 proteins are needed to establish basal expression levels of several ABA-responsive genes, suggesting that these chaperones might also be involved in ABA signaling events. Plants overexpressing HSC70-1 or with reduced HSP90.2 activity are hypersensitive to ABA in seed germination assays, suggesting that several chaperone complexes with distinct substrates might tune tissue-specific responses to ABA and the other biotic and abiotic stimuli studied. This study demonstrates that the HSC70/HSP90 machinery is important for stomatal closure and serves essential functions in plants to integrate signals from their biotic and abiotic environments.
A Small Zinc Finger Thylakoid Protein Plays a Role in Maintenance of Photosystem II in Arabidopsis thaliana
Authors: Lu Yan , Hall David A. , Last Robert L.
Published: May 2011

This work identifies LOW QUANTUM YIELD OF PHOTOSYSTEM II1 (LQY1), a Zn finger protein that shows disulfide isomerase activity, interacts with the photosystem II (PSII) core complex, and may act in repair of photodamaged PSII complexes. Two mutants of an unannotated small Zn finger containing a thylakoid membrane protein of Arabidopsis thaliana (At1g75690; LQY1) were found to have a lower quantum yield of PSII photochemistry and reduced PSII electron transport rate following high-light treatment. The mutants dissipate more excess excitation energy via nonphotochemical pathways than wild type, and they also display elevated accumulation of reactive oxygen species under high light. After high-light treatment, the mutants have less PSII–light-harvesting complex II supercomplex than wild-type plants. Analysis of thylakoid membrane protein complexes showed that wild-type LQY1 protein comigrates with the PSII core monomer and the CP43-less PSII monomer (a marker for ongoing PSII repair and reassembly). PSII repair and reassembly involve the breakage and formation of disulfide bonds among PSII proteins. Interestingly, the recombinant LQY1 protein demonstrates a protein disulfide isomerase activity. LQY1 is more abundant in stroma-exposed thylakoids, where key steps of PSII repair and reassembly take place. The absence of the LQY1 protein accelerates turnover and synthesis of PSII reaction center protein D1. These results suggest that the LQY1 protein may be involved in maintaining PSII activity under high light by regulating repair and reassembly of PSII complexes.
On the merits and feasibility of wildlife monitoring for conservation: a case study from Katavi National Park, Tanzania
Authors: Caro Tim
Published: May 2011

Although long‐term monitoring is viewed as an essential part of conserving wildlife populations, it is currently carried out in surprisingly few protected areas in Africa. Here, data from a 16‐year vehicle transect monitoring programme in Katavi National Park, western Tanzania, are presented. These data provide information on large mammal densities, identify declines in populations of several large mammal species as based on encounter rates, support worrying trends observed in aerial census data and shed light on the effectiveness of recent changes in legal protection. Ground and aerial surveys confirmed that waterbuck, topi, warthog, lion and spotted hyaena populations are all in decline and that this should be a cause for concern. Counting animals by driving vehicle transects is relatively easy and inexpensive to carry out, and data here show that such counts have several pay‐offs for conservation managers especially in identifying population declines; counts should be employed more often in East Africa and elsewhere.
Drug−disease interaction: Crohn's disease elevates verapamil plasma concentrations but reduces response to the drug proportional to disease activity
Authors: Sanaee Forough , Clements John D. , Waugh Alistair W. G. , Fedorak Richard N. , Lewanczuk Richard , Jamali Fakhreddin
Published: May 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Inflammatory conditions such as Crohn's disease are associated with cardiovascular complications. Inflammation also substantially reduces clearance of some cardiovascular drugs. It has also been shown that in rheumatoid arthritis, an elevation in verapamil concentration does not result in increased response.

WHAT THIS STUDY ADDS

• A reduced response upon increased verapamil concentration in another inflammatory condition, inflammatory bowel disease, with different aetiology from arthritis was found. Interestingly, however, a mere affliction with the disease is not sufficient to alter pharmacokinetics and pharmacodynamics since we found that the alteration is a function of disease severity. There is a remarkable reverse correlation between the disease severity and response to verapamil. Our observation suggests a complex relationship between pharmacokinetics and pharmacodynamics which may have implications beyond the disease and the drug studied herein.

AIM Inflammation is involved in the pathogenesis of cardiovascular diseases that includes reduced response to pharmacotherapy due to altered pharmacokinetics and pharmacodynamics. It is not known if these effects exist in general in all inflammatory conditions. It also remains unknown whether in a given population the effect is a function of disease severity. We investigated whether pharmacokinetics and pharmacodynamics of a typical calcium channel inhibitor are influenced by Crohn's disease (CD), a disease for which the disease severity can be readily ranked.

METHODS We administered 80 mg verapamil orally to (i) healthy control subjects (n= 9), (ii) patients with clinically quiescent CD (n= 22) and (iii) patients with clinically active CD (n= 14). Serial analysis of verapamil enantiomers (total and plasma unbound), blood pressure and electrocardiograms were recorded over 8 h post dose. The severity of CD was measured using the Harvey‐Bradshaw Index.

RESULTS CD substantially and significantly increased plasma verapamil concentration and in a stereoselective fashion (S, 9‐fold; R, 2‐fold). The elevated verapamil concentration, however, failed to result in an increased verapamil pharmacodynamic effect so that the patients with elevated verapamil concentration demonstrated no significant increase in response measured as PR interval and blood pressure. Instead, the greater the disease severity, the lower was the drug potency to prolong PR interval (r= 0.86, P < 0.0006),

CONCLUSIONS CD patients with severe disease may not respond to cardiovascular therapy with calcium channel blockers. Reducing the severity increases response despite reduced drug concentration. This observation may have therapeutic implication beyond the disease and the drug studies herein.
What is the best long‐term management strategy for patients with primary adrenal insufficiency?
Authors: Quinkler Marcus , Hahner Stefanie
Published: May 2011

Primary adrenal insufficiency is treated with glucocorticoid and mineralocorticoid replacement therapy. Recent data revealed that health‐related quality of life in adrenal insufficiency is impaired in many patients and that patients with adrenal insufficiency are also threatened by an increased mortality and morbidity. This may be caused by inadequate glucocortiocid therapy and adrenal crisis. Therefore, the optimization of hormone replacement therapy remains one of the most challenging tasks in endocrinology because it is largely based on clinical grounds because of the lack of objective assessment tools. This article provides answers to the important daily clinical questions, such as correct dose finding, dose adaptation in special situations, e g, pregnancy, improvement of quality of life and measures for protection from adrenal crisis. Other important aspects discussed are side effects of glucocortiocid replacement therapy and interactions with other drugs.
Effects of food components on the antimicrobial activity of polypropylene surfaces containing silver ions (Ag+)
Authors: Ilg Yvonne , Kreyenschmidt Judith
Published: May 2011

The aim of this study was to investigate the influence of food components on the antimicrobial properties of surfaces containing silver. The antimicrobial activity of a polypropylene compound with a zirconium phosphate–based ceramic ion exchange resin containing silver was investigated by comparing the surface count of bacteria on sample and reference surfaces. Different food components were added to the inocula to investigate their influence on the extent of antimicrobial activity in comparison with pure inoculum (Pseudomonas fluorescens in saline solution). In the experiments with pure inoculum, a marked reduction in bacterial counts on samples containing silver was observed (7.4 log10 units). However, protein‐rich food strongly reduced or completely inhibited the antimicrobial activity of silver. Almost all other tested components from the carbohydrate or lipid group did not affect the antimicrobial activity. Overall, the effect and the risks of materials containing silver needs to be analysed individually for the respective application.
Chemical, antioxidant and antibacterial study of Brazilian fruits
Authors: Haminiuk Charles Windson Isidoro , Plata‐Oviedo Manuel Salvador Vicente , Guedes Amanda Roman , Stafussa Ana Paula , Bona Evandro , Carpes Solange Teresinha
Published: May 2011

In this study, the antioxidant capability, total phenolic content and antimicrobial activity of ethanolic extracts of seven fruits from the Brazilian Atlantic Forest were evaluated. The conditions for the extraction of crude phenolics from the fruits were determined using an experimental factorial design. Total phenolic content, 1,1‐diphenyl‐2‐picrylhydrazyl radical (DPPH•) scavenging activity and β‐carotene‐linoleic acid couple oxidation assays were used to evaluate the antioxidant properties of the extracts. In addition, antimicrobial activity was screened using two Gram‐negative bacteria (Escherichia coli and Klebsiella pneumoniae) and one Gram‐positive bacterium (Staphylococcus aureus). All native fruits assayed in this study have high potential as natural antioxidant sources. Among the seven fruits evaluated, Jabuticaba and Uvaia had the highest antioxidant activity in the DPPH• and of β‐carotene‐linoleic acid coupled oxidation assays. In the biological assay, K. pneumoniae was the most sensitive microorganism to the fruit extracts, and the Jabuticaba extract had a slight inhibitory effect against this Gram‐positive bacterium.
Effects of added phenolics on the storage stability of avocado and coconut oils
Authors: Sun‐Waterhouse Dongxiao , Thakorlal Jessica , Zhou Jing
Published: May 2011

This study investigated the effects of added phenolics on the storage stability of avocado and coconut oils. Avocado and coconut oils in the absence (control oil) and presence (treated oil) of caffeic acid (CA) or p‐coumaric acid (pCA) were stored at 20 and 60 °C for 50 days. The total phenolic content, peroxide value, p‐anisidine value (p‐AV), free fatty acids (FFAs) and FA composition of the obtained oils were examined on days 0, 7, 15, 23, 35 and 50. Results showed that storage at 60 °C accelerated oil oxidation, and the CA or pCA helped preserve avocado and coconut oils to different extents. CA and pCA protected some desirable unsaturated fatty acids at 60 °C, but facilitated the hydrolysis of triglycerides. Substantially extractable phenolics were still detected in the treated oils after either storage. Incorporation of phenolics into oil products is feasible and beneficial for increasing oil stability and nutritional value.
Factors affecting Penicillium roquefortii (Penicillium glaucum) in internally mould ripened cheeses: implications for pre‐packed blue cheeses
Authors: Fairclough Andrew C. , Cliffe Dawn E. , Knapper Sarah
Published: May 2011

The amount and vivid colour of blue veins of internally mould ripened cheeses are desirable quality characteristics. It is therefore important that there is a sufficient amount of veining and that it maintains its blue appearance to be appealing to consumers therefore leading to maximised sales potential and profit for the manufacturing company. Optimum in vitro growth mimicking the conditions typically found in pre‐packed blue cheeses, and using lactose as the sole carbon source, was facilitated by a gas mixture of 5% oxygen/0% carbon dioxide/balance nitrogen). The work undertaken in this study determined that the factors for optimum in vitro growth of Penicillium roquefortii (strain PRB6) were: a temperature of 20 ± 1 °C, pH of 6.0 ± 0.1, and a relative humidity of 70 ± 0.1%. Further in vitro studies have also shown that the increasing ‘in‐pack’ carbon dioxide concentration not only depresses the growth of P. roquefortii but also affects immature conidiospore pigmentation (no effect has been seen on mature conidiospore pigmentation). The implications of this study suggest that the majority of pre‐packed internally mould ripened blue cheeses on sale in supermarkets are packaged in inappropriate materials. For some cheeses (e.g. the Roquefort‐type cheeses) this is not an issue since these are packed in a much more mature state and some loss of veining colour is not appreciably noticeable.
Development of an evidence‐based scoring system (HF‐IS) to assess the quality of heart failure programmes for patients postdischarge from hospital
Authors: Driscoll Andrea , Tonkin Andrew , Stewart Andrew , Thompson David R , Worrall‐Carter Linda , Riegel Barbara , Hare David L , Davidson Patricia M , Stewart Simon
Published: May 2011

Aim.  The aim of this study was to develop a potential scoring algorithm for interventions in a chronic heart failure management programme – the Heart Failure Intervention Score – to facilitate quality improvement and programme auditing.

Background.  The overall efficacy of chronic heart failure management programmes has been demonstrated in several meta‐analyses. However, meta‐analyses did not determine individual interventions in a programme that resulted in beneficial patient outcomes.

Design.  A prospective cross‐sectional survey design.

Method.  All chronic heart failure management programmes in Australia (n = 62), identified by a national register, were surveyed to determine programme characteristics and interventions.

Results.  Of the 62 national chronic heart failure management programmes, 48 (77%) completed the survey and 27 individual interventions were identified. Variability in the use of the key interventions was common among the programmes. Each intervention was given an arbitrary weighted score according to the level of supportive evidence available and a total score calculated. Programmes were then categorised into low or high complexity based on several interventions implemented and their weighted score. A total score of ≥190 (median = 178, interquartile range 176–195) was used to divide programmes into two groups. Nine programmes were categorised into high Heart Failure Intervention Score group and majority of these were based in the acute hospital setting (78%). In the low Heart Failure Intervention Score group, there were 39 programmes of which there were a higher proportion of community‐based programmes (38%) and programmes in small community hospitals (10%).

Conclusion.  The Heart Failure Intervention Score provides a potential evidence‐based quality improvement tool through which a set of minimum standards can be developed. Implementation of the Heart Failure Intervention Score provides guidance to programme coordinators to enable monitoring of standards of heart failure programmes, which may potentially result in better patient outcomes.

Relevance to clinical practice.  The Heart Failure Intervention Score is an evidence‐based tool that can be easily used by heart failure programme coordinators to ensure that their programme is evidence‐based, which will improve the quality of their programme and potentially programme outcomes.
Assessing quality of life of older people with dementia in long‐term care: a comparison of two self‐report measures
Authors: Moyle Wendy , Gracia Natalie , Murfield Jenny E , Griffiths Susan G , Venturato Lorraine
Published: May 2011

Aims and objectives.  This study sought to compare two well‐known and well‐used self‐report quality of life questionnaires in terms of completion rates, reliability and assessment of quality of life.

Background.  People with dementia have a meaningful experience of quality of life and several disease‐specific instruments have been designed to capture self‐report assessments.

Design.  A quantitative survey design, with a convenience sample of older people with dementia from four long‐term care facilities.

Method.  Sixty‐one participants were recruited for survey on the Dementia Quality of Life questionnaire and the Quality of Life in Alzheimer’s Disease questionnaire.

Results.  The Quality of Life in Alzheimer’s Disease questionnaire had a higher rate of completion (98·4%) than the Dementia Quality of Life questionnaire (68·9%). Those unable to complete the latter measure had significantly greater cognitive impairment (F1,59 = 30·35, p < 0·001) than those completing the measure. Internal reliability was good for the Quality of Life in Alzheimer’s Disease questionnaire (0·86), but there were varying levels found for the five Dementia Quality of Life questionnaire subscales (0·79–0·48). The Quality of Life in Alzheimer’s Disease questionnaire was significantly correlated with all the Dementia Quality of Life questionnaire subscales and overall item.

Conclusions.  Although it is recognised that there is no superior instrument in assessing quality of life, this study found both the Quality of Life in Alzheimer’s Disease questionnaire and Dementia Quality of Life questionnaire to be useful self‐report instruments.

Relevance to clinical practice.  Assessment of quality of life should include the perspective of the person with dementia. The Quality of Life in Alzheimer’s Disease questionnaire and Dementia Quality of Life questionnaire appear to measure similar aspects of quality of life. Where assessments are sought from participants with more advanced cognitive and functional impairment, it may be favourable to employ the Quality of Life in Alzheimer’s Disease questionnaire.
17β‐Oestradiol Regulation of Gonadotrophin‐Releasing Hormone Neuronal Excitability
Authors: Rønnekleiv O. K. , Bosch M. A. , Zhang C.
Published: May 2011

17β‐Oestradiol (E2) is essential for cyclical gonadotrophin‐releasing hormone (GnRH) neuronal activity and secretion. In particular, E2increases the excitability of GnRH neurones during the afternoon of pro‐oestrus in the rodent, which is associated with increased synthesis and secretion of GnRH. It is well established that E2regulates the activity of GnRH neurones through both presynaptic and postsynaptic mechanisms. E2significantly modulates the mRNA expression of numerous ion channels in GnRH neurones and alters the associated endogenous conductances, including potassium (KATP, A‐type) currents and low‐voltage T‐type and high‐voltage L‐type calcium currents. Notably, KATPchannels are critical for maintaining GnRH neurones in a hyperpolarised state for recruiting the T‐type calcium channels, which are important for burst firing in GnRH neurones. In addition, there are other critical channels contributing to burst firing pattern, including the small conductance Ca2+‐activated K+channels that may be modulated by E2. Despite these advances, the cellular mechanisms underlying the cyclical GnRH neuronal activity and GnRH release are largely unknown. Ultimately, the ensemble of both pre‐ and postsynaptic targets of the actions of E2will dictate the excitability and activity pattern of GnRH neurones.
Sex Steroids Control Neuroinflammatory Processes in the Brain: Relevance for Acute Ischaemia and Degenerative Demyelination
Authors: Kipp M. , Berger K. , Clarner T. , Dang J. , Beyer C.
Published: May 2011

Sex steroids have been demonstrated as powerful compounds to protect neurones and neural tissue from neurotoxic challenges and during neurodegeneration. A multitude of cellular actions have been attributed to female gonadal steroid hormones, including the regulation of pro‐survival and anti‐apoptotic factors, bioenergetic demands and radical elimination, growth factor allocation and counteracting against excitotoxicity. In recent years, immune‐modulatory and anti‐inflammatory characteristics of oestrogen and progesterone have also come under scrutiny. To date, each of these physiological responses has been considered to be partially and selectively integrated in the mediation of steroid‐mediated cell protection and tested in suitable animal models and in vitro systems. To what extent these individual effects contribute to the overall neural protection remains sketchy. One idea is that a battery of cellular mechanisms operates at the same time. On the other hand, interactions and the control of the brain‐intrinsic and peripheral immune system may play an additional and perhaps pioneering function in this scenario, notwithstanding the importance of secondary adjuvant mechanisms. In the present review, we highlight neuroprotective effects of oestrogen and progesterone in two different disease models of the brain, namely acute ischaemic and demyelination damage, which represent the most common acute and degenerative neurological disorders in humans. Besides other inflammatory parameters, we discuss the idea that chemokine expression and signalling appear to be early hallmarks in both diseases and are positively affected by sex steroids. In addition, the complex interplay with local brain‐resident immune‐competent cells appears to be controlled by the steroid environment.
The N‐terminal part of Als1 protein from Candida albicans specifically binds fucose‐containing glycans
Authors: Donohue Dagmara S. , Ielasi Francesco S. , Goossens Katty V. Y. , Willaert Ronnie G.
Published: May 2011

The opportunistic pathogen Candida albicans expresses on its surface Als (Agglutinin like sequence) proteins, which play an important role in the adhesion to host cells and in the development of candidiasis. The binding specificity of these proteins is broad, as they can bind to various mammalian proteins, such as extracellular matrix proteins, and N‐ and E‐cadherins. The N‐terminal part of Als proteins constitutes the substrate‐specific binding domain and is responsible for attachment to epithelial and endothelial cells. We have used glycan array screening to identify possible glycan receptors for the binding domain of Als1p‐N. Under those conditions, Als1p‐N binds specifically to fucose‐containing glycans, which adds a lectin function to the functional diversity of the Als1 protein. The binding between Als1p‐N and BSA‐fucose glycoconjugate was quantitatively characterized using surface plasmon resonance, which demonstrated a weak millimolar affinity between Als1p‐N and fucose. Furthermore, we have also quantified the affinity of Als1p‐N to the extracellular matrix proteins proteins fibronectin and laminin, which is situated in the micromolar range. Surface plasmon resonance characterization of Als1p‐N–Als1p‐N interaction was in the micromolar affinity range.
The SLH‐domain protein BslO is a determinant of Bacillus anthracis chain length
Authors: Anderson Valerie J. , Kern Justin W. , McCool Justin W. , Schneewind Olaf , Missiakas Dominique
Published: May 2011

The Gram‐positive pathogen Bacillus anthracis grows in characteristic chains of individual, rod‐shaped cells. Here, we report the cell‐separating activity of BslO, a putative N‐acetylglucosaminidase bearing three N‐terminal S‐layer homology (SLH) domains for association with the secondary cell wall polysaccharide (SCWP). Mutants with an insertional lesion in the bslO gene exhibit exaggerated chain lengths, although individual cell dimensions are unchanged. Purified BslO complements this phenotype in trans, effectively dispersing chains of bslO‐deficient bacilli without lysis and localizing to the septa of vegetative cells. Compared with the extremely long chain lengths of csaB bacilli, which are incapable of binding proteins with SLH‐domains to SCWP, bslO mutants demonstrate a chaining phenotype that is intermediate between wild‐type and csaB. Computational simulation suggests that BslO effects a non‐random distribution of B. anthracis chain lengths, implying that all septa are not equal candidates for separation.
Signalling through the IL‐2 receptor γc peptide (CD132) is essential for the expression of immunity to Plasmodium chabaudi adami blood‐stage malaria
Authors: WEIDANZ W. P. , LaFLEUR G. , KITA‐YARBRO A. , NELSON K. , BURNS J. M.
Published: May 2011

A genetic dissection approach was employed to determine whether the IL‐2 receptor complex (IL‐2R) comprised of α, β and γ chains is required for the suppression of Plasmodium chabaudi adami parasitemia. Blood‐stage infections in IL‐2Rγc−/y mice failed to cure with parasitemia remaining elevated for >50 days indicating the IL‐2Rγc through which all members of the γc family of cytokines signal has an essential role in protective immunity against blood‐stage malarial parasites. In contrast, the curing of parasitemia in IL‐2/15Rβ−/− mice, deficient in both IL‐2 and IL‐15 signalling was significantly delayed but did occur, indicating that neither cytokine plays an essential role in parasite clearance. Moreover, the observation that the time course of parasitemia in IL‐15−/− mice was nearly identical to that seen in controls suggests that the parasitemia‐suppressing role of stimulating through the IL‐2/15Rβ chain is owing to IL‐2 signalling and not a redundant function of IL‐15.
Antibodies directed against merozoite surface protein‐6 are induced by natural exposure to Plasmodium falciparum in a low transmission environment
Authors: JORDAN S. J. , OLIVEIRA A. L. , NEAL A. T. , HERNANDEZ J. N. , BRANCH O. H. , RAYNER J. C.
Published: May 2011

Malaria caused by Plasmodium falciparum is a major cause of global infant mortality, and there is currently no licensed vaccine that provides protection against infection or disease. Several P. falciparum vaccine targets have undergone early testing, but many more candidates remain with little data to support their development. Plasmodium falciparum Merozoite Surface Protein 6 (PfMSP6) is a candidate of particular interest because it is a member of the PfMSP3 multi‐gene family, raising the possibility that vaccine‐induced immune responses could cross‐react across multiple family members. However, few immunoepidemiological studies of PfMSP6 have been carried out to measure domain‐specific anti‐PfMSP6 responses. This study investigated anti‐PfMSP6 responses in P. falciparum‐infected individuals from the Peruvian Amazon, using two different PfMSP6 N‐terminal allele antigens and a single C‐terminal domain antigen, and compared the responses with both PfMSP6 genotyping data and anti‐PfMSP3 response data that had been previously generated for the same samples. Anti‐PfMSP6 responses were detected despite the low transmission setting, but were less frequent and of considerably lower intensity than anti‐PfMSP3 responses. There was a positive correlation between anti‐PfMSP3 and PfMSP6 responses, suggesting that the possibility that PfMSP3 family antigens could induce cross‐reactive responses requires further detailed investigation.
Morphological reinforcement, ancient introgressive hybridization and species delimitation in African stem‐borer species of the genus Sesamia Guenée (Lepidoptera: Noctuidae)
Authors: MOYAL PASCAL , LE RÜ BRUNO , VAN DEN BERG JOHNNY , RATNADASS ALAIN , CUGALA DOMINGOS , MATAMA‐KAUMA TEDDY , PALLANGYO BEATRICE , CONLONG DESMOND , DEFABACHEW BELAY
Published: May 2011

Species delimitation, an issue central to systematics and biodiversity studies, is addressed in the epunctifera group of the stem borer genus Sesamia Guenée (Lepidoptera: Noctuidae). This group is composed of four sub‐Saharan species: Sesamia poephaga Tams & Bowden; Sesamia epunctifera Hampson; Sesamia penniseti Tams & Bowden; and Sesamia poebora Tams & Bowden, the taxonomic status of which was unclear. The first species was considered a possible synonym of the second, and the third species was considered a possible synonym of the fourth. An analysis combining morphological, ecological and molecular data enables us to conclude that S. epunctifera and S. poephaga are different species, and that S. poebora is a synonym of S. penniseti. Two new species were discovered: Sesamia firmatasp.n. and Sesamia veronicasp.n.Sesamia firmatasp.n. has atypical genitalic morphology, suggesting a strong selection resulting in a reinforcement of pre‐zygotic isolation. Some specimens previously identified as S. penniseti on the basis of morphology are sisters to S. epunctifera on the mitochondrial tree, and are connected to S. penniseti on the nuclear tree. The mitochondrial distance from S. penniseti and S. epunctifera is 7.6% and 3.9%, respectively, suggesting an ancient mitochondrial introgression from S. epunctifera into S. penniseti. The possible causes of the reinforcement and introgressive hybridization are discussed. This case of mitochondrial introgression, uncommon in Lepidoptera, in which females are the heterogametic sex, may be an exception to Haldane's rule. The hybrid is assigned the rank of species and named Sesamia pennipunctasp.n.
Suppression of the rice heterotrimeric G protein β‐subunit gene, RGB1, causes dwarfism and browning of internodes and lamina joint regions
Authors: Utsunomiya Yuzuko , Samejima Chihiro , Takayanagi Yoshiyuki , Izawa Yuki , Yoshida Takahisa , Sawada Yuka , Fujisawa Yukiko , Kato Hisaharu , Iwasaki Yukimoto
Published: May 2011

In the present study, we investigated the function of the heterotrimeric G protein β‐subunit (Gβ) gene (RGB1) in rice. RGB1 knock‐down lines were generated in the wild type and d1‐5, a mutant deficient for the heterotrimeric G protein α‐subunit (Gα) gene (RGA1). Both transgenic lines showed browning of the lamina joint regions and nodes that could be attributed to a reduction of RGB1 function, as the abnormality was not observed in d1‐5. The RGB1 knock‐down lines generated in d1‐5 were shorter, suggesting RGB1 to be a positive regulator of cellular proliferation, in addition to RGA1. The number of sterile seeds also increased in both RGB1 knock‐down lines. These results suggest that Gβγ and Gα cooperatively function in cellular proliferation and seed fertility. We discuss the potential predominant role of RGB1 in G protein signaling in rice.
The transcription factor EMISSION OF BENZENOIDS II activates the MYB ODORANT1 promoter at a MYB binding site specific for fragrant petunias
Authors: Van Moerkercke Alex , Haring Michel A. , Schuurink Robert C.
Published: May 2011

Fragrance production in petunia flowers is highly regulated. Two transcription factors, ODORANT1 (ODO1) and EMISSION OF BENZENOIDS II (EOBII) have recently been identified as regulators of the volatile benzenoid/phenylpropanoid pathway in petals. Unlike the non‐fragrant Petunia hybrida cultivar R27, the fragrant cultivar Mitchell highly expresses ODO1. Using stable reporter lines, we identified the 1.2‐kbp ODO1 promoter from Mitchell that is sufficient for tissue‐specific, developmental and rhythmic expression. This promoter fragment can be activated in non‐fragrant R27 petals, indicating that the set of trans‐acting factors driving ODO1 expression is conserved in these two petunias. Conversely, the 1.2‐kbp ODO1 promoter of R27 is much less active in Mitchell petals. Transient transformation of 5′ deletion and chimeric Mitchell and R27 ODO1 promoter reporter constructs in petunia petals identified an enhancer region, which is specific for the fragrant Mitchell cultivar and contains a putative MYB binding site (MBS). Mutations in the MBS of the Mitchell promoter decreased overall promoter activity by 50%, highlighting the importance of the enhancer region. We show that EOBII binds and activates the ODO1 promoter via this MBS, establishing a molecular link between these two regulators of floral fragrance biosynthesis in petunia.
Perioperative renal failure in pediatric heart transplant recipients: Outcome and risk factors
Authors: Tang Liwen , Du Wei , L'Ecuyer Thomas J.
Published: May 2011

Tang L, Du W, L’Ecuyer TJ. Perioperative renal failure in pediatric heart transplant recipients: Outcome and risk factors. Pediatr Transplantation 2011: 15: 430–436. © 2011 John Wiley & Sons A/S.

Abstract:  PRF is encountered in 10–13% of adult heart transplants. Only one study of a single center’s experience with PRF has been reported in pediatric patients. This study examines the effect of PRF on pediatric heart transplant outcome using the UNOS database. A total of 3598 patients met inclusion criteria, of whom 254 (7%) had PRF. The PRF group comprised 31 recipients requiring PRE and 223 recipients requiring POST. Compared with No‐PRF patients, PRE patients had similar survival rate and POST patients had decreased survival rate at 30 days, one, five, and 10‐yr post‐transplant (p < 0.001). PRF patients also had significantly lower graft survival at one, five, and 10 yr (p < 0.001). Risk factors for developing PRF included ECMO, ventilator, and inotropic support at listing and CHD as the listing diagnosis. PRF increased the duration of hospital stay and the incidence of chronic severe renal dysfunction. PRF that requires POST (whether or not it began pretransplant) has a significant negative impact on pediatric heart transplant outcome. Specific characteristics identify patients at particular high risk of developing PRF.
Tetramer monitoring to assess risk factors for recurrent cytomegalovirus reactivation and reconstitution of antiviral immunity post allogeneic hematopoietic stem cell transplantation
Authors: Borchers S. , Luther S. , Lips U. , Hahn N. , Kontsendorn J. , Stadler M. , Buchholz S. , Diedrich H. , Eder M. , Koehl U. , Ganser A. , Mischak‐Weissinger E.
Published: May 2011

S. Borchers, S. Luther, U. Lips, N. Hahn, J. Kontsendorn, M. Stadler, S. Buchholz, H. Diedrich, M. Eder, U. Koehl, A. Ganser, E. Mischak‐ Weissinger. Tetramer monitoring to assess risk factors for recurrent cytomegalovirus reactivation and reconstitution of antiviral immunity post allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis 2011: 13: 222–236. All rights reserved

Background. Reactivation of cytomegalovirus (CMV) is a major cause of morbidity after allogeneic hematopoietic stem cell transplantation (HSCT). In healthy individuals, virus‐specific T cells (CMV‐CTL) control the reactivation of latent CMV. The monitoring of virus‐epitope‐binding CD8+ T cells using major histocompatibility complex‐I‐peptide complexes (tetramers) has recently been established, allowing assessment of the reconstitution of CMV‐CTL post HSCT.

Patients and methods. In order to study immune reconstitution and reactivation control through CMV‐CTL, we regularly monitored all patients undergoing allogeneic HSCT in our department for 2 years, who matched at least 1 of 6 commercially available tetramers for common human leukocyte antigen (HLA) types. To verify risk factors for CMV reactivations in our cohorts, clinical characteristics of all patients transplanted within the last 10 years were included in statistical analyses determining the relative risk for single and recurrent CMV reactivations.

Results. As expected, CMV serostatus, HLA match, and donor source significantly influenced the risk of recurrent CMV reactivation. Applying CMV‐CTL tetramer monitoring for 2 years allowed the monitoring of 114 (85%) of 134 patients, by testing a set of tetramers representing 6 epitopes from 3 different CMV proteins. The presence of CMV‐CTL before day +50 and their expansion post reactivation seem to protect against recurrent CMV reactivations. The mean number of CMV‐CTL by day +100 was >5‐fold higher in the recipient CMV‐positive/donor‐positive (R+/D+) group (91/μL) compared with the R+/D− (13/μL) and the R−/D+(2/μL) group. Seventy‐nine percent of patients from the R+/D+ setting recovered >10 CMV‐CTL per μL by day +100, while almost 50% of the other groups failed to mount a CMV‐specific response by that time (R+/D−: 58%; R−/D+: 43%).

Conclusion. Tetramer monitoring can help to predict (recurrent) CMV reactivation and is a useful approach to monitor individual patients with increased risk for recurrent reactivation post HSCT; thus, it could help to identify patients in need of adoptive transfer of CMV‐CTL or to optimize the use of antiviral drugs.