bluuebunny/crossref_metadata_2025 huggingface dataset:
Temperature dependence of the band gap of perovskite semiconductor compound CsSnI3
Authors: Yu Chonglong , Chen Zhuo , J. Wang Jian , Pfenninger William , Vockic Nemanja , Kenney John T. , Shum Kai
Published: September 2011

The temperature dependence of the bandgap of perovskite semiconductor compound CsSnI3 is determined by measuring excitonic emission at low photoexcitation in a temperature range from 9 to 300 K. The bandgap increases linearly as the lattice temperature increases with a linear coefficient of 0.35 meV K−1. This behavior is distinctly different than that in most of tetrahedral semiconductors. First-principles simulation is employed to predict the bandgap change with the rigid change of lattice parameters under a quasi-harmonic approximation. It is justified that the thermal contribution dominates to the bandgap variation with temperature, while the direct contribution of electron-phonon interaction is conjectured to be negligible likely due to the unusual large electron effective mass for this material.
A traveling wave decelerator for neutral polar molecules
Authors: Meek Samuel A. , Parsons Maxwell F. , Heyne Georg , Platschkowski Viktor , Haak Henrik , Meijer Gerard , Osterwalder Andreas
Published: September 2011

Recently, a decelerator for neutral polar molecules has been presented that operates on the basis of macroscopic, three-dimensional, traveling electrostatic traps [A. Osterwalder, S. A. Meek, G. Hammer, H. Haak, and G. Meijer, Phys. Rev. A 81, 051401 (2010)]10.1103/PhysRevA.81.051401. In the present paper, a complete description of this decelerator is given, with emphasis on the electronics and the mechanical design. Experimental results showing the transverse velocity distributions of guided molecules are shown and compared to trajectory simulations. An assessment of non-adiabatic losses is made by comparing the deceleration signals from 13CO with those from 12CO and with simulated signals.
A tunable rotational energy harvester for low frequency vibration
Authors: Jang Seon-Jun , Kim In-Ho , Jung Hyung-Jo , Lee Yoon-Pyo
Published: September 2011

The tunable single-degree-of-freedom rotational energy harvester is proposed. The device is the combination of the rotational energy harvester and the suspended weight. Thus, it can harvest the electrical power from the translational base excitation associated with low frequency and large amplitude. Further, its natural frequency can be changeable by manipulating the size of the reel (i.e., geometrical tunability). The characteristics of the proposed device are investigated through numerical simulation and experimental test.
Intern culture, internal resistance: uptake of peer review in two Australian hospital internship programs
Authors: Owen Cathy , Mathews Paul W. , Phillips Christine , Ramsey Wayne , Corrigan Gerry , Bassett Mark , Wenzel Johannes
Published: September 2011

Objective.
To compare the uptake of peer review among interns in mandatory and voluntary peer-review programs.

Population.
All first and second year graduates (n = 105) in two Australian hospitals.

Main outcome measures.
Completion of peer review, and reported responses by doctors to peer review.

Results.
Eight of sixty interns undertaking the mandated program completed all steps. In the voluntary program, none of 45 interns did so. Resistance to peer review occurred at all stages of the trial, from the initial briefing sessions to the provision of peer-review reports.

Discussion.
Hospital internship is a critical period for the development of professional identity among doctors. We hypothesise that resistance to peer review among novice doctors reflects a complex tension between the processes underpinning the development of a group professional identity in hospital, and a managerial drive for personal reflection and accountability. Peer review may be found threatening by interns because it appears to run counter to collegiality or ‘team culture’. In this study, resistance to peer review represented a low-cost strategy in which the interns’ will could be asserted against management.

Conclusion.
To enhance uptake, peer review should be structured as key to clinical development, and modelled as a professional behaviour by higher-status colleagues.

What is known about this topic?
In non-clinical settings, peer review can lead to improvements in performance. Studies in the US and Canada have demonstrated that junior doctors in hospital have low rates of uptake of peer review.

What does this paper add?
In Australia, junior doctors had low rates of engagement with both mandatory and voluntary peer review. Peer review may be resisted because it threatens to undermine the collegiate atmosphere among hospital peers.

What are the implications for practice?
Peer review should be modelled as professional behaviour by higher-status colleagues, especially registrars and consultants, and presented as central to improvement in clinical skills.
Root growth of lupins is more sensitive to waterlogging than wheat
Authors: Bramley Helen , Tyerman Stephen D. , Turner David W. , Turner Neil C.
Published: September 2011

In south-west Australia, winter grown crops such as wheat and lupin often experience transient waterlogging during periods of high rainfall. Wheat is believed to be more tolerant to waterlogging than lupins, but until now no direct comparisons have been made. The effects of waterlogging on root growth and anatomy were compared in wheat (Triticum aestivum L.), narrow-leafed lupin (Lupinus angustifolius L.) and yellow lupin (Lupinus luteus L.) using 1 m deep root observation chambers. Seven days of waterlogging stopped root growth in all species, except some nodal root development in wheat. Roots of both lupin species died back progressively from the tips while waterlogged. After draining the chambers, wheat root growth resumed in the apical region at a faster rate than well-drained plants, so that total root length was similar in waterlogged and well-drained plants at the end of the experiment. Root growth in yellow lupin resumed in the basal region, but was insufficient to compensate for root death during waterlogging. Narrow-leafed lupin roots did not recover; they continued to deteriorate. The survival and recovery of roots in response to waterlogging was related to anatomical features that influence internal oxygen deficiency and root hydraulic properties.
Maternal recognition of pregnancy in the horse: a mystery still to be solved
Authors: Klein C. , Troedsson M. H. T.
Published: September 2011

Maternal recognition of pregnancy in the horse is the sum of events leading to maintenance of pregnancy; in a narrow sense, maternal recognition of pregnancy refers to the physiological process by which the lifespan of the corpus luteum is prolonged. The horse is one of the few domestic species in which the conceptus-derived pregnancy recognition signal has not been identified. The presence of the conceptus reduces pulsatile prostaglandin F2α secretion by the endometrium during early gestation in the mare, partly attributed to the reduced expression of cyclooxygenase-2. Cyclooxygenase-2 has therefore been suggested as one of the regulators of endometrial prostaglandin F2α release modified by the antiluteolytic factor secreted by the conceptus. In addition, altered oxytocin responsiveness has been implicated in the adjustment of prostaglandin release in pregnant mares. While conceptus mobility has proven to be essential for establishment of pregnancy, conceptus-derived oestrogens and prostaglandins, principally prostaglandin E2, have not been confirmed as the critical antiluteolytic factor. Various ways to induce prolonged luteal function in the non-pregnant mare will be highlighted in the current review, specifically, how they may pertain to the process of maternal recognition of pregnancy. Furthermore, recently published microarray experiments comparing the transcriptome of pregnant and non-pregnant endometria and different stages of conceptus development will be reviewed. Findings include the prevention of conceptus adhesion, the provision of nutrients to the conceptus and the avoidance of immunological rejection, among others.
Life expectancy of HIV-positive adults: a review
Authors: May Margaret T. , Ingle Suzanne M.
Published: September 2011

We review studies estimating life expectancy (LE), the average number of additional years a person can expect to live, for HIV-positive adults and show variation by sociodemographic factors and level of immunosuppression. The LE of patients starting antiretroviral therapy early in the course of HIV infection and attaining restoration of a normal CD4 count may approach that of the general population. Improvements in treatment and the associated increase in LE imply that increasing numbers of HIV-positive patients will live to older age. Late diagnosis and presentation to care and treatment not concordant with guidelines contribute to reducing LE.
Mesenchymal stem cells impair in vivo T-cell priming by dendritic cells
Authors: Chiesa Sabrina , Morbelli Silvia , Morando Sara , Massollo Michela , Marini Cecilia , Bertoni Arinna , Frassoni Francesco , Bartolomé Soraya Tabera , Sambuceti Gianmario , Traggiai Elisabetta , Uccelli Antonio
Published: September 2011

Dendritic cells (DC) are highly specialized antigen-presenting cells characterized by the ability to prime T-cell responses. Mesenchymal stem cells (MSC) are adult stromal progenitor cells displaying immunomodulatory activities including inhibition of DC maturation in vitro. However, the specific impact of MSC on DC functions, upon in vivo administration, has never been elucidated. Here we show that murine MSC impair Toll-like receptor-4 induced activation of DC resulting in the inhibition of cytokines secretion, down-regulation of molecules involved in the migration to the lymph nodes, antigen presentation to CD4+T cells, and cross-presentation to CD8+T cells. These effects are associated with the inhibition of phosphorylation of intracellular mitogen-activated protein kinases. Intravenous administration of MSC decreased the number of CCR7 and CD49dβ1 expressing CFSE-labeled DC in the draining lymph nodes and hindered local antigen priming of DO11.10 ovalbumin-specific CD4+T cells. Upon labeling of DC with technetium-99m hexamethylpropylene amine oxime to follow their in vivo biodistribution, we demonstrated that intravenous injection of MSC blocks, almost instantaneously, the migration of subcutaneously administered ovalbumin-pulsed DC to the draining lymph nodes. These findings indicate that MSC significantly affect DC ability to prime T cells in vivo because of their inability to home to the draining lymph nodes and further confirm MSC potentiality as therapy for immune-mediated diseases.
Motifs emerge from function in model gene regulatory networks
Authors: Burda Z. , Krzywicki A. , Martin O. C. , Zagorski M.
Published: September 2011

Gene regulatory networks allow the control of gene expression patterns in living cells. The study of network topology has revealed that certain subgraphs of interactions or “motifs” appear at anomalously high frequencies. We ask here whether this phenomenon may emerge because of the functions carried out by these networks. Given a framework for describing regulatory interactions and dynamics, we consider in the space of all regulatory networks those that have prescribed functional capabilities. Markov Chain Monte Carlo sampling is then used to determine how these functional networks lead to specific motif statistics in the interactions. In the case where the regulatory networks are constrained to exhibit multistability, we find a high frequency of gene pairs that are mutually inhibitory and self-activating. In contrast, networks constrained to have periodic gene expression patterns (mimicking for instance the cell cycle) have a high frequency of bifan-like motifs involving four genes with at least one activating and one inhibitory interaction.
Behavior-specific changes in transcriptional modules lead to distinct and predictable neurogenomic states
Authors: Chandrasekaran Sriram , Ament Seth A. , Eddy James A. , Rodriguez-Zas Sandra L. , Schatz Bruce R. , Price Nathan D. , Robinson Gene E.
Published: September 2011

Using brain transcriptomic profiles from 853 individual honey bees exhibiting 48 distinct behavioral phenotypes in naturalistic contexts, we report that behavior-specific neurogenomic states can be inferred from the coordinated action of transcription factors (TFs) and their predicted target genes. Unsupervised hierarchical clustering of these transcriptomic profiles showed three clusters that correspond to three ecologically important behavioral categories: aggression, maturation, and foraging. To explore the genetic influences potentially regulating these behavior-specific neurogenomic states, we reconstructed a brain transcriptional regulatory network (TRN) model. This brain TRN quantitatively predicts with high accuracy gene expression changes of more than 2,000 genes involved in behavior, even for behavioral phenotypes on which it was not trained, suggesting that there is a core set of TFs that regulates behavior-specific gene expression in the bee brain, and other TFs more specific to particular categories. TFs playing key roles in the TRN include well-known regulators of neural and behavioral plasticity, e.g.,
Creb
, as well as TFs better known in other biological contexts, e.g.,
NF-κB
(immunity). Our results reveal three insights concerning the relationship between genes and behavior. First, distinct behaviors are subserved by distinct neurogenomic states in the brain. Second, the neurogenomic states underlying different behaviors rely upon both shared and distinct transcriptional modules. Third, despite the complexity of the brain, simple linear relationships between TFs and their putative target genes are a surprisingly prominent feature of the networks underlying behavior.
A necessary and sufficient condition for Ricci shrinkers to have positive AVR
Authors: Chow Bennett , Lu Peng , Yang Bo
Published: September 2011

In this short paper we observe that a recent result of C.-W. Chen meshes well with earlier work of H.-D. Cao and D.-T. Zhou, O. Munteanu, J. Carrillo and L. Ni, and S.-J. Zhang. We give a necessary and sufficient condition for complete noncompact shrinking gradient Ricci solitons to have positive asymptotic volume ratio.
Syndetic sets and amenability
Authors: Paulsen Vern
Published: September 2011

We prove that if an infinite, discrete semigroup has the property that every right syndetic set is left syndetic, then the semigroup has a left invariant mean. We prove that the weak

∗
*

-closed convex hull of the two-sided translates of every bounded function on an infinite discrete semigroup contains a constant function. Our proofs use the algebraic properties of the Stone-Cech compactification.
Loss of derivatives for systems of complex vector fields and sums of squares
Authors: Khanh Tran Vu , Pinton Stefano , Zampieri Giuseppe
Published: September 2011

We discuss, both for systems of complex vector fields and for sums of squares, the phenomenon discovered by Kohn of hypoellipticity with loss of derivatives.
Pension Transfers and farm household technical efficiency: Evidence from South Africa
Authors: Lovo Stefania
Published: September 2011

This article analyzes the effect of entitlements from the Old Age Pension Program of South Africa on household technical efficiency using a sample of farm households in South Africa's KwaZulu‐Natal province. The analysis is at the household level, and off‐farm activities are considered as additional outputs in a nonparametric estimation of technical efficiency. This approach captures the jointness between farm and off‐farm activities. The pension's effect is identified by exploiting the age‐eligibility criteria in the pension program. Results show a positive effect of the pension and suggest that this large cash transfer can improve households’ ability to make use of the best available technologies.
Kaviar: an accessible system for testing SNV novelty
Authors: Glusman Gustavo , Caballero Juan , Mauldin Denise E. , Hood Leroy , Roach Jared C.
Published: September 2011

Summary: With the rapidly expanding availability of data from personal genomes, exomes and transcriptomes, medical researchers will frequently need to test whether observed genomic variants are novel or known. This task requires downloading and handling large and diverse datasets from a variety of sources, and processing them with bioinformatics tools and pipelines. Alternatively, researchers can upload data to online tools, which may conflict with privacy requirements. We present here Kaviar, a tool that greatly simplifies the assessment of novel variants. Kaviar includes: (i) an integrated and growing database of genomic variation from diverse sources, including over 55 million variants from personal genomes, family genomes, transcriptomes, SNV databases and population surveys; and (ii) software for querying the database efficiently.

Availability: Kaviar is programmed in Perl and offered free of charge as Open Source Software. Kaviar may be used online as a programmatic web service or downloaded for local use from http://db.systemsbiology.net/kaviar. The database is also provided.

Contact:  gustavo@systemsbiology.org

Supplementary Information:  Supplementary data are available at Bioinformatics online.
HHfrag: HMM-based fragment detection using HHpred
Authors: Kalev Ivan , Habeck Michael
Published: September 2011

Motivation: Over the last decade, both static and dynamic fragment libraries for protein structure prediction have been introduced. The former are built from clusters in either sequence or structure space and aim to extract a universal structural alphabet. The latter are tailored for a particular query protein sequence and aim to provide local structural templates that need to be assembled in order to build the full-length structure.

Results: Here, we introduce HHfrag, a dynamic HMM-based fragment search method built on the profile–profile comparison tool HHpred. We show that HHfrag provides advantages over existing fragment assignment methods in that it: (i) improves the precision of the fragments at the expense of a minor loss in sequence coverage; (ii) detects fragments of variable length (6–21 amino acid residues); (iii) allows for gapped fragments and (iv) does not assign fragments to regions where there is no clear sequence conservation. We illustrate the usefulness of fragments detected by HHfrag on targets from most recent CASP.

Availability: A web server for running HHfrag is available at http://toolkit.tuebingen.mpg.de/hhfrag. The source code is available at http://www.eb.tuebingen.mpg.de/departments/1-protein-evolution/michael-habeck/HHfrag.tar.gz

Contact:  michael.habeck@tuebingen.mpg.de

Supplementary Information:  Supplementary data are available at Bioinformatics online.
TFRank: network-based prioritization of regulatory associations underlying transcriptional responses
Authors: Gonçalves Joana P. , Francisco Alexandre P. , Mira Nuno P. , Teixeira Miguel C. , Sá-Correia Isabel , Oliveira Arlindo L. , Madeira Sara C.
Published: September 2011

Motivation: Uncovering mechanisms underlying gene expression control is crucial to understand complex cellular responses. Studies in gene regulation often aim to identify regulatory players involved in a biological process of interest, either transcription factors coregulating a set of target genes or genes eventually controlled by a set of regulators. These are frequently prioritized with respect to a context-specific relevance score. Current approaches rely on relevance measures accounting exclusively for direct transcription factor–target interactions, namely overrepresentation of binding sites or target ratios. Gene regulation has, however, intricate behavior with overlapping, indirect effect that should not be neglected. In addition, the rapid accumulation of regulatory data already enables the prediction of large-scale networks suitable for higher level exploration by methods based on graph theory. A paradigm shift is thus emerging, where isolated and constrained analyses will likely be replaced by whole-network, systemic-aware strategies.

Results: We present TFRank, a graph-based framework to prioritize regulatory players involved in transcriptional responses within the regulatory network of an organism, whereby every regulatory path containing genes of interest is explored and incorporated into the analysis. TFRank selected important regulators of yeast adaptation to stress induced by quinine and acetic acid, which were missed by a direct effect approach. Notably, they reportedly confer resistance toward the chemicals. In a preliminary study in human, TFRank unveiled regulators involved in breast tumor growth and metastasis when applied to genes whose expression signatures correlated with short interval to metastasis.

Availability: Prototype at http://kdbio.inesc-id.pt/software/tfrank/.

Contact:  jpg@kdbio.inesc-id.pt; sara.madeira@ist.utl.pt;

Supplementary Information:  Supplementary data are available at Bioinformatics online.
An investigation of human vs. technology-induced variation in catchability for a selection of European fishing fleets
Authors: Mahévas Stéphanie , Vermard Youen , Hutton Trevor , Iriondo Ane , Jadaud Angélique , Maravelias Christos D. , Punzón Antonio , Sacchi Jacques , Tidd Alex , Tsitsika Efthymia , Marchal Paul , Goascoz Nicolas , Mortreux Serge , Roos David
Published: September 2011

Mahévas, S., Vermard, Y., Hutton, T., Iriondo, A., Jadaud, A., Maravelias, C. D., Punzón, A., Sacchi, J., Tidd, A., Tsitsika, E., Marchal, P., Goascoz, N., Mortreux, S., and Roos, D. 2011. An investigation of human vs. technology-induced variation in catchability for a selection of European fishing fleets. – ICES Journal of Marine Science, 68: 2252–2263. The impact of the fishing effort exerted by a vessel on a population depends on catchability, which depends on population accessibility and fishing power. The work investigated whether the variation in fishing power could be the result of the technical characteristics of a vessel and/or its gear or whether it is a reflection of inter-vessel differences not accounted for by the technical attributes. These inter-vessel differences could be indicative of a skipper/crew experience effect. To improve understanding of the relationships, landings per unit effort (lpue) from logbooks and technical information on vessels and gears (collected during interviews) were used to identify variables that explained variations in fishing power. The analysis was undertaken by applying a combination of generalized additive models and generalized linear models to data from several European fleets. The study highlights the fact that taking into account information that is not routinely collected, e.g. length of headline, weight of otter boards, or type of groundrope, will significantly improve the modelled relationships between lpue and the variables that measure relative fishing power. The magnitude of the skipper/crew experience effect was weaker than the technical effect of the vessel and/or its gear.
Bayesian parameter inference for stochastic biochemical network models using particle Markov chain Monte Carlo
Authors: Golightly Andrew , Wilkinson Darren J.
Published: September 2011

Computational systems biology is concerned with the development of detailed mechanistic models of biological processes. Such models are often stochastic and analytically intractable, containing uncertain parameters that must be estimated from time course data. In this article, we consider the task of inferring the parameters of a stochastic kinetic model defined as a Markov (jump) process. Inference for the parameters of complex nonlinear multivariate stochastic process models is a challenging problem, but we find here that algorithms based on particle Markov chain Monte Carlo turn out to be a very effective computationally intensive approach to the problem. Approximations to the inferential model based on stochastic differential equations (SDEs) are considered, as well as improvements to the inference scheme that exploit the SDE structure. We apply the methodology to a Lotka–Volterra system and a prokaryotic auto-regulatory network.
Manipulation of particles in two dimensions using phase controllable ultrasonic standing waves
Authors: Courtney C. R. P. , Ong C.-K. , Drinkwater B. W. , Bernassau A. L. , Wilcox P. D. , Cumming D. R. S.
Published: September 2011

The ability to manipulate dense micrometre-scale objects in fluids is of interest to biosciences with a view to improving analysis techniques and enabling tissue engineering. A method of trapping micrometre-scale particles and manipulating them on a two-dimensional plane is proposed and demonstrated. Phase-controlled counter-propagating waves are used to generate ultrasonic standing waves with arbitrary nodal positions. The acoustic radiation force drives dense particles to pressure nodes. It is shown analytically that a series of point-like traps can be produced in a two-dimensional plane using two orthogonal pairs of counter-propagating waves. These traps can be manipulated by appropriate adjustment of the relative phases. Four 5 MHz transducers (designed to minimize reflection) are used as sources of counter-propagating waves in a water-filled cavity. Polystyrene beads of 10 μm diameter are trapped and manipulated. The relationship between trapped particle positions and the relative phases of the four transducers is measured and shown to agree with analytically derived expressions. The force available is measured by determining the response to a sudden change in field and found to be 30 pN, for a 30 V
pp
input, which is in agreement with the predictions of models of the system. A scalable fabrication approach to producing devices is demonstrated.
The evolution of sex differences in mate searching when females benefit: new theory and a comparative test
Authors: McCartney J. , Kokko H. , Heller K.-G. , Gwynne D. T.
Published: September 2011

Sexual selection is thought to have led to searching as a profitable, but risky way of males obtaining mates. While there is great variation in which sex searches, previous theory has not considered search evolution when both males and females benefit from multiple mating. We present new theory and link it with data to bridge this gap. Two different search protocols exist between species in the bush-cricket genusPoecilimon(Orthoptera): females search for calling males, or males search for calling females.Poecilimonmales also transfer a costly nuptial food gift to their mates during mating. We relate variations in searching protocols to variation in nuptial gift size among 32Poecilimontaxa. As predicted, taxa where females search produce significantly larger nuptial gifts than those where males search. Our model and results show that search roles can reverse when multiple mating brings about sufficiently strong material benefits to females.
CcpA coordinates central metabolism and biofilm formation in Staphylococcus epidermidis
Authors: Sadykov Marat R. , Hartmann Torsten , Mattes Theodoric A. , Hiatt Megan , Jann Naja J. , Zhu Yefei , Ledala Nagender , Landmann Regine , Herrmann Mathias , Rohde Holger , Bischoff Markus , Somerville Greg A.
Published: September 2011

Staphylococcus epidermidis is an opportunistic bacterium whose infections often involve the formation of a biofilm on implanted biomaterials. In S. epidermidis, the exopolysaccharide facilitating bacterial adherence in a biofilm is polysaccharide intercellular adhesin (PIA), whose synthesis requires the enzymes encoded within the intercellular adhesin operon (icaADBC). In
vitro, the formation of S. epidermidis biofilms is enhanced by conditions that repress tricarboxylic acid (TCA) cycle activity, such as growth in a medium containing glucose. In many Gram-positive bacteria, repression of TCA cycle genes in response to glucose is accomplished by catabolite control protein A (CcpA). CcpA is a member of the GalR–LacI repressor family that mediates carbon catabolite repression, leading us to hypothesize that catabolite control of S. epidermidis biofilm formation is indirectly regulated by CcpA-dependent repression of the TCA cycle. To test this hypothesis, ccpA deletion mutants were constructed in strain 1457 and 1457-acnA and the effects on TCA cycle activity, biofilm formation and virulence were assessed. As anticipated, deletion of ccpA derepressed TCA cycle activity and inhibited biofilm formation; however, ccpA deletion had only a modest effect on icaADBC transcription. Surprisingly, deletion of ccpA in strain 1457-acnA, a strain whose TCA cycle is inactive and where icaADBC transcription is derepressed, strongly inhibited icaADBC transcription. These observations demonstrate that CcpA is a positive effector of biofilm formation and icaADBC transcription and a repressor of TCA cycle activity.
The Sink-Specific Plastidic Phosphate Transporter PHT4;2 Influences Starch Accumulation and Leaf Size in Arabidopsis
Authors: Irigoyen Sonia , Karlsson Patrik M. , Kuruvilla Jacob , Spetea Cornelia , Versaw Wayne K.
Published: September 2011

Nonphotosynthetic plastids are important sites for the biosynthesis of starch, fatty acids, and amino acids. The uptake and subsequent use of cytosolic ATP to fuel these and other anabolic processes would lead to the accumulation of inorganic phosphate (Pi) if not balanced by a Pi export activity. However, the identity of the transporter(s) responsible for Pi export is unclear. The plastid-localized Pi transporter PHT4;2 of Arabidopsis (Arabidopsis thaliana) is expressed in multiple sink organs but is nearly restricted to roots during vegetative growth. We identified and used pht4;2 null mutants to confirm that PHT4;2 contributes to Pi transport in isolated root plastids. Starch accumulation was limited in pht4;2 roots, which is consistent with the inhibition of starch synthesis by excess Pi as a result of a defect in Pi export. Reduced starch accumulation in leaves and altered expression patterns for starch synthesis genes and other plastid transporter genes suggest metabolic adaptation to the defect in roots. Moreover, pht4;2 rosettes, but not roots, were significantly larger than those of the wild type, with 40% greater leaf area and twice the biomass when plants were grown with a short (8-h) photoperiod. Increased cell proliferation accounted for the larger leaf size and biomass, as no changes were detected in mature cell size, specific leaf area, or relative photosynthetic electron transport activity. These data suggest novel signaling between roots and leaves that contributes to the regulation of leaf size.
Assessment of serum vascular endothelial growth factor and nail fold capillaroscopy changes in systemic lupus erythematosus with and without cutaneous manifestations
Authors: MONEIB Hoda A. , SALEM Samar A. M. , ALY Dalia G. , KHEDR Heba T. M. , WAFAEY Hanaa A. , HASSAN Hanan E.
Published: September 2011

Angiogenesis and microvascular endothelial injury play a role in the pathogenesis of systemic lupus erythematosus (SLE). Vascular endothelial growth factor (VEGF), a key regulator of angiogenesis, and nail fold capillaroscopy (NFC) have been investigated in few studies in SLE with no reports targeting SLE with cutaneous manifestations. To evaluate NFC changes and VEGF serum level in relation to disease activity in SLE patients with versus without cutaneous manifestations. Thirty SLE patients (15 with cutaneous manifestations [group I], 15 without [group II]) and 15 healthy controls were evaluated for VEGF serum levels, NFC changes and were related to disease activity. VEGF serum levels were significantly higher in patients than controls (median and interquartile range [IQR]: 2110.77, 471.09–4714.30 vs 60.00, 14–366, respectively, P < 0.0001). VEGF cut‐off value to predict SLE patients was more than 293 and to detect moderate and severe SLE activity was more than 422 pg/mL and more than 3800 pg/mL, respectively. Serum VEGF levels increased with increased disease activity (P < 0.05). It was significantly higher in group I than group II (median and IQR: 2624.74, 1801.39–4141.70 vs 862.50, 180–2426.95, respectively, P < 0.05). Mean serum VEGF was significantly higher with NFC score 3 than 1 (P = 0.008). NFC score and SLE activity were significantly associated in patients (P < 0.05). Serum VEGF is significantly elevated in SLE patients with cutaneous manifestations and its cut‐off values to detect different activity grades of SLE are identified. Abnormalities in NFC reflect the extent of microvascular involvement in SLE.
Artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in pregnancy: absorption, bioavailability, disposition and disease effects
Authors: McGready Rose , Phyo Aung Pyae , Rijken Marcus J. , Tarning Joel , Lindegardh Niklas , Hanpithakpon Warunee , Than Hla Hla , Hlaing Nathar , Zin Naw Thida , Singhasivanon Pratap , White Nicholas J. , Nosten François
Published: September 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Lowered plasma concentrations of artesunate have been reported in uncomplicated malaria in pregnancy which could risk the life of the mother and fetus.

• The reason for lowered plasma concentrations in pregnancy is unexplained.

• Oral artesunate is hydrolyzed rapidly in the stomach to the biologically active metabolite dihyroartemisinin.

WHAT THIS STUDY ADDS

• Following i.v. artesunate administration for malaria in pregnancy the disposition of artesunate and dihydroartemisinin were similar to controls (the same women studied post partum without malaria).

• Higher concentrations of artesunate and dihydroartemisinin were observed after oral administration i.e the disease reduced the pre‐systemic metabolism of artesunate.

• This study did not confirm previous reports and is reassuring regarding current dosing for artesunate in pregnancy.

AIM To determine if reported lower plasma concentrations of artemisinin derivatives for malaria in pregnancy result from reduced oral bioavailability, expanded volume of distribution or increased clearance.

METHODS In a sequentially assigned crossover treatment study, pregnant women with uncomplicated falciparum malaria received i.v. artesunate (i.v. ARS) (4 mg kg−1) on the first day and oral ARS (4 mg kg−1) on the second, or, oral on the first and i.v. on the second, in both groups followed by oral ARS (4 mg kg−1 day−1) for 5 days. Plasma concentrations of ARS and dihyroartemisinin (DHA) were measured by liquid chromatography‐mass‐spectrometry on days 0, 1, 2 and 6. Controls were the same women restudied when healthy (3 months post partum).

RESULTS I.v. ARS administration resulted in similar ARS and DHA pharmacokinetics in pregnant women with malaria (n= 20) and in controls (n= 14). Oral administration resulted in higher total drug exposure in pregnancy [AUC (95% CI) in (ng ml−1 h)/(mg kg−1)] of 55.1 (30.1, 100.0) vs. 26.5 (12.2, 54.3) for ARS, P= 0.002 and 673 (386, 1130) vs. 523 (351, 724) for DHA, P= 0.007. The corresponding median absolute oral bioavailability (F%) was 21.7 (12.6, 75.1) vs. 9.9 (6.0, 36.81) for ARS (P= 0.046) and 77.0 (42.2, 129) vs. 72.7 (42.0, 87.7) for DHA, P= 0.033. Total DHA exposure was lower at day 6 in pregnant women with malaria (P < 0.001) compared with day 0 or 1, but not in the controls (P= 0.084).

CONCLUSIONS This study demonstrates the effects of malaria on oral ARS drug disposition are greater than those of pregnancy. This probably results from a disease related reduction in first pass metabolism. The data are reassuring regarding current dosing recommendations.
Nitric oxide and related enzymes in asthma: relation to severity, enzyme function and inflammation
Authors: Yamamoto M. , Tochino Y. , Chibana K. , Trudeau J. B. , Holguin F. , Wenzel S. E.
Published: September 2011

Background

Exhaled nitric oxide (FeNO) associates with asthma and eosinophilic inflammation. However, relationships between nitric oxide synthases, arginase, FeNO, asthma severity and inflammation remain poorly understood.

Objectives

To determine the relationships of iNOS expression/activation and arginase 2 expression with asthma severity, FeNO, nitrotyrosine (NT) and eosinophilic inflammation.

Methods

Bronchial brushings and sputum were obtained from 25 normal controls, eight mild/no inhaled corticosteroids (ICS), 16 mild‐moderate/with ICS and 35 severe asthmatics. The FeNO was measured the same day by ATS/ERS standards. The iNOS, arginase2 mRNA/protein and NT protein were measured in lysates from bronchial brushings by quantitative real‐time PCR and Western blot. Induced sputum differentials were obtained.

Results

Severe asthma was associated with the highest levels of iNOS protein and mRNA, although the index of iNOS mRNA to arginase2 mRNA most strongly differentiated severe from milder asthma. When evaluating NO‐related enzyme functionality, iNOS mRNA/protein expression both strongly predicted FeNO (r = 0.61, P < 0.0001 for both). Only iNOS protein predicted NT levels (r = 0.48, P = 0.003) with the strongest relationship in severe asthma (r = 0.61, P = 0.009). The iNOS protein, FeNO and NT, all correlated with sputum eosinophils, but the relationships were again strongest in severe asthma. Controlling for arginase 2 mRNA/protein did not impact any functional outcome.

Conclusions and Clinical Relevance

These data suggest that while iNOS expression from epithelial brushings is highest in severe asthma, factors controlling arginase2 mRNA expression significantly improve differentiation of severity. In contrast, functionality of the NO pathway as measured by FeNO, NT and eosinophilic inflammation, is strongly associated with iNOS expression alone, particularly in severe asthma.
The role of mitochondria in energy production for human sperm motility
Authors: Piomboni P. , Focarelli R. , Stendardi A. , Ferramosca A. , Zara V.
Published: September 2011

Mitochondria of spermatozoa are different from the corresponding organelles of somatic cells, in both their morphology and biochemistry. The biochemical differences are essentially related to the existence of specific enzyme isoforms, which are characterized by peculiar kinetic and regulatory properties. As mitochondrial energy metabolism is a key factor supporting several sperm functions, these organelles host critical metabolic pathways during germ cell development and fertilization. Furthermore, spermatozoa can use different substrates, and therefore activate different metabolic pathways, depending on the available substrates and the physico‐chemical conditions in which they operate. This versatility is critical to ensure fertilization success. However, the most valuable aspect of mitochondria function in all types of cells is the production of chemical energy in the form of ATP which can be used, in the case of spermatozoa, for sustaining sperm motility. The latter, on the other hand, represents one of the major determinants of male fertility. Accordingly, the presence of structural and functional alterations in mitochondria from asthenozoospermic subjects confirms the important role played by these organelles in energy maintenance of sperm motility. The present study gives an overview of the current knowledge on the energy‐producing metabolic pathways operating inside human sperm mitochondria and critically analyse the differences with respect to somatic mitochondria. Such a comparison has also been carried out between the functional characteristics of human sperm mitochondria and those of other mammalian species. A deeper understanding of mitochondrial energy metabolism could open up new avenues of investigation in bioenergetics of human sperm mitochondria, both in physiological and pathological conditions.
Early loss to follow‐up of recently diagnosed HIV‐infected adults from routine pre‐ART care in a rural district hospital in Kenya: a cohort study
Authors: Hassan Amin S. , Fielding Katherine L. , Thuo Nahashon M. , Nabwera Helen M. , Sanders Eduard J. , Berkley James A.
Published: September 2011

Objective  To determine the rate and predictors of early loss to follow‐up (LTFU) for recently diagnosed HIV‐infected, antiretroviral therapy (ART)‐ineligible adults in rural Kenya.

Methods  Prospective cohort study. Clients registering for HIV care between July 2008 and August 2009 were followed up for 6 months. Baseline data were used to assess predictors of pre‐ART LTFU (not returning for care within 2 months of a scheduled appointment), LTFU before the second visit and LTFU after the second visit. Logistic regression was used to determine factors associated with LTFU before the second visit, while Cox regression was used to assess predictors of time to LTFU and LTFU after the second visit.

Results  Of 530 eligible clients, 178 (33.6%) were LTFU from pre‐ART care (11.1/100 person‐months). Of these, 96 (53.9%) were LTFU before the second visit. Distance (>5 km vs. <1 km: adjusted hazard ratio 2.6 [1.9–3.7], P < 0.01) and marital status (married vs. single: 0.5 [0.3–0.6], P < 0.01) independently predicted pre‐ART LTFU. Distance and marital status were independently associated with LTFU before the second visit, while distance, education status and seasonality showed weak evidence of predicting LTFU after the second visit. HIV disease severity did not predict pre‐ART LTFU.

Conclusions  A third of recently diagnosed HIV‐infected, ART‐ineligible clients were LTFU within 6 months of registration. Predictors of LTFU among ART‐ineligible clients are different from those among clients on ART. These findings warrant consideration of an enhanced pre‐ART care package aimed at improving retention and timely ART initiation.
Deficiency of CRTAP in non‐lethal recessive osteogenesis imperfecta reduces collagen deposition into matrix
Authors: Valli M , Barnes AM , Gallanti A , Cabral WA , Viglio S , Weis MA , Makareeva E , Eyre D , Leikin S , Antoniazzi F , Marini JC , Mottes M
Published: September 2011

Valli M, Barnes AM, Gallanti A, Cabral WA, Viglio S, Weis MA, Makareeva E, Eyre D, Leikin S, Antoniazzi F, Marini JC, Mottes M. Deficiency of CRTAP in non‐lethal recessive osteogenesis imperfecta reduces collagen deposition into matrix.

Deficiency of any component of the ER‐resident collagen prolyl 3‐hydroxylation complex causes recessive osteogenesis imperfecta (OI). The complex modifies the α1(I)Pro986 residue and contains cartilage‐associated protein (CRTAP), prolyl 3‐hydroxylase 1 (P3H1) and cyclophilin B (CyPB). Fibroblasts normally secrete about 10% of CRTAP. Most CRTAP mutations cause a null allele and lethal type VII OI. We identified a 7‐year‐old Egyptian boy with non‐lethal type VII OI and investigated the effects of his null CRTAP mutation on collagen biochemistry, the prolyl 3‐hydroxylation complex, and collagen in extracellular matrix. The proband is homozygous for an insertion/deletion in CRTAP (c.118_133del16insTACCC). His dermal fibroblasts synthesize fully overmodified type I collagen, and 3‐hydroxylate only 5% of α1(I)Pro986. CRTAP transcripts are 10% of control. CRTAP protein is absent from proband cells, with residual P3H1 and normal CyPB levels. Dermal collagen fibril diameters are significantly increased. By immunofluorescence of long‐term cultures, we identified a severe deficiency (10–15% of control) of collagen deposited in extracellular matrix, with disorganization of the minimal fibrillar network. Quantitative pulse‐chase experiments corroborate deficiency of matrix deposition, rather than increased matrix turnover. We conclude that defects of extracellular matrix, as well as intracellular defects in collagen modification, contribute to the pathology of type VII OI.
Differential mRNA Expression and Promoter Methylation Status of SYCP3 Gene in Testes of Yaks and Cattle‐Yaks
Authors: Wang S , Pan Z , Zhang Q , Xie Z , Liu H , Li Q
Published: September 2011

Contents

Synaptonemal complex protein 3 (SYCP3) is a DNA‐binding protein located on the lateral elements of the synaptonemal complex. This protein plays an important role in homologous chromosome pairing and is necessary for male meiosis of spermatogenesis. To further understand the SYCP3 gene function and its relationship to cattle‐yak male sterility, we investigated the characteristics of the bovine SYCP3 (bSYCP3) gene as well as its transcription level and epigenetic modification status. The bSYCP3 gene encodes a 225‐amino acid protein with the Cor1 motif and two coiled‐coil‐forming regions, homologous with other mammals (59–77% identity overall). Real‐time PCR analysis indicated that the expression level of bSYCP3 mRNA in yak testes was significantly higher than that in cattle‐yak (p < 0.05). The methylation level of the bSYCP3 promoter (mainly 7th, 13th and 17th CpG sites) in cattle‐yaks (40%) was significantly higher than that in yaks (0%) (p < 0.05). This suggests that bSYCP3 plays an important role in meiosis of bovine spermatogenesis; further, interspecific hybridization between yak and cattle might influence bSYCP3 gene expression in cattle‐yak testes, which might be influenced by bSYCP3 gene promoter methylation.
Reversible control of biofilm formation by Cellulomonas spp. in response to nitrogen availability
Authors: Young Jenna M. , Leschine Susan B. , Reguera Gemma
Published: September 2011

The microbial degradation of cellulose contributes greatly to the cycling of carbon in terrestrial environments and feedbacks to the atmosphere, a process that is highly responsive to nitrogen inputs. Yet how key groups of cellulolytic microorganisms adaptively respond to the global conditions of nitrogen limitation and/or anthropogenic or climate nitrogen inputs is poorly understood. The actinobacterial genus Cellulomonas is of special interest because it incorporates the only species known to degrade cellulose aerobically and anaerobically. Furthermore, despite their inability to fix nitrogen, they are active decomposers in nitrogen‐limited environments. Here we show that nitrogen limitation induced biofilm formation in Cellulomonas spp., a process that was coupled to carbon sequestration and storage in a curdlan‐type biofilm matrix. The response was reversible and the curdlan matrix was solubilized and used as a carbon and energy source for biofilm dispersal once nitrogen sources became available. The biofilms attached strongly to cellulosic surfaces and, despite the growth limitation, produced cellulases and degraded cellulose more efficiently. The results show that biofilm formation is a competitive strategy for carbon and nitrogen acquisition and provide valuable insights linking nitrogen inputs to carbon sequestration and remobilization in terrestrial environments.
Towards a taxonomy ofBacteriaandArchaeabased on interactive and cumulative data repositories
Authors: Rosselló‐Móra Ramon
Published: September 2011

Taxonomy in the second decade of the 21st century is benefiting from technological advances in molecular microbiology, especially those related to genomics. Gene and genome databases are significantly increasing due to intense research activities in the field of molecular ecology and genomics. Taxa, and especially species, are tailored by means of the recognition of a phylogenetic, genomic and phenotypic coherence that reveal their uniqueness in the classification schema. Phylogenetic coherence is mainly revealed by means of 16S rRNA gene analyses for which curated databases such as EzTaxon and LTP provide a valuable tool for tree reconstruction to taxonomy users. On the other hand,in silicofull or partial genomic sequence comparisons are called on to substitute cumbersome techniques such as DNA–DNA hybridization (DDH) to genomically circumscribe species. DDH similarity values around 70% would be equivalent to ANI values of 96%. Finally, finding an exclusive phenotypic property for the taxa to be classified is of paramount relevance to producing an operative and predictive classification system. The current methods used for taxonomic classification require significant laboratory experimentation, and generally will not produce interactive databases. The new high‐throughput metabolomic technologies, such as ICR‐FT and MALDI‐TOF mass spectrometry methods, open the door to the construction of metabolic databases for taxonomic purposes. It is to be foreseen that, in the future, taxonomists will benefit significantly from public databases speeding up the classification process. However, serious effort will be needed to harmonize them and to prevent inaccurate material.