bluuebunny/crossref_metadata_2025_split huggingface dataset:
TED, an Autonomous and Rare Maize Transposon of theMutatorSuperfamily with a High Gametophytic Excision Frequency
Authors: Li Yubin , Harris Linda , Dooner Hugo K. 
Published: September 2013

AbstractMutator (Mu) elements, one of the most diverse superfamilies of DNA transposons, are found in all eukaryotic kingdoms, but are particularly numerous in plants. Most of the present knowledge on the transposition behavior of this superfamily comes from studies of the maize (Zea mays) Mu elements, whose transposition is mediated by the autonomous Mutator-Don Robertson (MuDR) element. Here, we describe the maize element TED (for Transposon Ellen Dempsey), an autonomous cousin that differs significantly from MuDR. Element excision and reinsertion appear to require both proteins encoded by MuDR, but only the single protein encoded by TED. Germinal excisions, rare with MuDR, are common with TED, but arise in one of the mitotic divisions of the gametophyte, rather than at meiosis. Instead, transposition-deficient elements arise at meiosis, suggesting that the double-strand breaks produced by element excision are repaired differently in mitosis and meiosis. Unlike MuDR, TED is a very low-copy transposon whose number and activity do not undergo dramatic changes upon inbreeding or outcrossing. Like MuDR, TED transposes mostly to unlinked sites and can form circular transposition products. Sequences closer to TED than to MuDR were detected only in the grasses, suggesting a rather recent evolutionary split from a common ancestor.
Topsoil removal improves various restoration treatments of a Mediterranean steppe (La Crau, southeast France)
Authors: Jaunatre Renaud , Buisson Elise , Dutoit Thierry 
Published: September 2013

AbstractQuestionCan topsoil removal improve restoration efficiency of several ecological engineering techniques (nurse species seeding, hay transfer and soil transfer) for restoring a Mediterranean steppe, species‐rich plant community?LocationLa Crau area, southeast France (Provence).MethodsAfter the rehabilitation of a 357‐ha herbaceous, sheep‐grazed rangeland suitable for threatened steppe birds in a formerly abandoned industrial orchard in the last French Mediterranean steppe (La Crau area), four experimental treatments were applied, with or without topsoil removal. Topsoil was removed on a 5000‐m² area and the four treatments (control, nurse species seeding, hay transfer and soil transfer) were applied within this area where topsoil was removed and within the area where topsoil was not removed. Three years later, soil chemistry, soil seed bank, vegetation cover and height, plant species richness, composition and diversity were compared.ResultsRemoving topsoil partly restored soil conditions and significantly reduced the non‐target seed bank. Moreover, species richness and similarity to the reference steppe was significantly increased with topsoil removal. Topsoil removal, combined with soil transfer and hay transfer, created a community that most closely resembled the reference during the study period.ConclusionIn order to restore plant community composition, topsoil removal is a relevant method to increase the efficiency of other ecological restoration techniques, especially those that strengthen dispersal processes.
Serious Hazards of Transfusion (SHOT) haemovigilance and progress is improving transfusion safety
Authors: Bolton‐Maggs Paula H. B. , Cohen Hannah 
Published: September 2013

SummaryThe Serious Hazards of Transfusion (SHOT) UK confidential haemovigilance reporting scheme began in 1996. Over the 16 years of reporting, the evidence gathered has prompted changes in transfusion practice from the selection and management of donors to changes in hospital practice, particularly better education and training. However, half or more reports relate to errors in the transfusion process despite the introduction of several measures to improve practice. Transfusion in the UK is very safe: 2·9 million components were issued in 2012, and very few deaths are related to transfusion. The risk of death from transfusion as estimated from SHOT data in 2012 is 1 in 322 580 components issued and for major morbidity, 1 in 21 413 components issued; the risk of transfusion‐transmitted infection is much lower. Acute transfusion reactions and transfusion‐associated circulatory overload carry the highest risk for morbidity and death. The high rate of participation in SHOT by National Health Service organizations, 99·5%, is encouraging. Despite the very useful information gained about transfusion reactions, the main risks remain human factors. The recommendations on reduction of errors through a ‘back to basics’ approach from the first annual SHOT report remain absolutely relevant today.
Non‐irradiated female survivors of childhood acute lymphoblastic leukaemia are at risk of long‐term increases in weight and body mass index
Authors: Harper Robert L. C. , Breene Richard A. L. , Gattens Michael , Williams Rachel M. , Murray Matthew J. 
Published: September 2013

SummaryWe report long‐term, including final height, auxological data from our retrospective study of non‐irradiated survivors of childhood acute lymphoblastic leukaemia (ALL). Body mass index (BMI) standard deviation score (SDS) increases in females, due to increased weight‐SDS, persisted to final height, with probable adverse long‐term health outcomes. In contrast, males demonstrated increased BMI‐SDS in follow‐up, due to reduced height‐SDS, not increased weight‐SDS, but such changes had resolved by final height. Childhood ALL survivors, particularly females, are therefore at potential increased risk of developing the metabolic syndrome during follow‐up. We recommend that strategies to minimize weight gain should be implemented during ALL treatment.
Temperatures and the growth and development of maize and rice: a review
Authors: Sánchez Berta , Rasmussen Anton , Porter John R 
Published: September 2013

AbstractBecause of global land surface warming, extreme temperature events are expected to occur more often and more intensely, affecting the growth and development of the major cereal crops in several ways, thus affecting the production component of food security. In this study, we have identified rice and maize crop responses to temperature in different, but consistent, phenological phases and development stages. A literature review and data compilation of around 140 scientific articles have determined the key temperature thresholds and response to extreme temperature effects for rice and maize, complementing an earlier study on wheat. Lethal temperatures and cardinal temperatures, together with error estimates, have been identified for phenological phases and development stages. Following the methodology of previous work, we have collected and statistically analysed temperature thresholds of the three crops for the key physiological processes such as leaf initiation, shoot growth and root growth and for the most susceptible phenological phases such as sowing to emergence, anthesis and grain filling. Our summary shows that cardinal temperatures are conservative between studies and are seemingly well defined in all three crops. Anthesis and ripening are the most sensitive temperature stages in rice as well as in wheat and maize. We call for further experimental studies of the effects of transgressing threshold temperatures so such responses can be included into crop impact and adaptation models.
Population genomic footprints of selection and associations with climate in natural populations of Arabidopsis halleri from the Alps
Authors: Fischer Martin C. , Rellstab Christian , Tedder Andrew , Zoller Stefan , Gugerli Felix , Shimizu Kentaro K. , Holderegger Rolf , Widmer Alex 
Published: September 2013

AbstractNatural genetic variation is essential for the adaptation of organisms to their local environment and to changing environmental conditions. Here, we examine genomewide patterns of nucleotide variation in natural populations of the outcrossing herb Arabidopsis halleri and associations with climatic variation among populations in the Alps. Using a pooled population sequencing (Pool‐Seq) approach, we discovered more than two million SNPs in five natural populations and identified highly differentiated genomic regions and SNPs using FST‐based analyses. We tested only the most strongly differentiated SNPs for associations with a nonredundant set of environmental factors using partial Mantel tests to identify topo‐climatic factors that may underlie the observed footprints of selection. Possible functions of genes showing signatures of selection were identified by Gene Ontology analysis. We found 175 genes to be highly associated with one or more of the five tested topo‐climatic factors. Of these, 23.4% had unknown functions. Genetic variation in four candidate genes was strongly associated with site water balance and solar radiation, and functional annotations were congruent with these environmental factors. Our results provide a genomewide perspective on the distribution of adaptive genetic variation in natural plant populations from a highly diverse and heterogeneous alpine environment.
Epigenetic programming of neuroendocrine systems during early life
Authors: Murgatroyd Chris 
Published: September 2013

New findings
What is the topic of this review?Behavioural epigenetics and its role in early‐life programming and adaptation is allowing us to understand how psychiatric diseases can develop through interactions of genes and environments.
What advances does it highlight?The ability of methyl of Methyl‐CpG binding protein 2 to regulate Avp gene expression, in response to early‐life stress, and induce DNA methylation, occurs through the recruitment of components of the epigenetic machinery.
Arginine vasopressin plays a pivotal role in the control of long‐lasting effects of early‐life stress on the brain. We previously reported that maternal separation in mice persistently upregulates Avp gene expression associated with reduced DNA methylation of a region in the Avp enhancer. This early‐life stress‐responsive region serves as a binding site for the methyl‐CpG binding protein 2, which in turn is controlled through neuronal activity. We also found that the ability of methyl‐CpG binding protein 2 to regulate transcription of the Avp gene and induce DNA methylation occured through the recruitment of components of the epigenetic machinery. Understanding the sequential events involved in the epigenetic regulation of a gene should allow for targeted approaches aimed at reprogramming expression during development and possibly later life.
Mechanisms contributing to cluster formation in the inferior olivary nucleus in brainstem slices from postnatal mice
Authors: Kølvraa Mathias , Müller Felix C. , Jahnsen Henrik , Rekling Jens C. 
Published: September 2013

Key points
One of the two main inputs to the cerebellum consists of climbing fibres from neurons in the inferior olivary nucleus (IO).
The IO spontaneously forms clusters of co‐active neurons in transverse brainstem slices from 1‐ to 2‐week‐old animals, coinciding with a critical time period in cerebellar development.
Here, we studied the cluster‐forming mechanisms, and find that randomly occurring spontaneous clusters overlap extensively, and contain 10 to hundreds of IO neurons with an average somatodendritic field size that is slightly smaller than the average IO cluster size.
Cluster formation is dependent on sodium action potentials and electrical coupling between IO neurons, and may spread with decreasing velocity and may involve active dendritic properties.
The results help us better understand the basic mechanism underlying cluster formation in the IO, which is an important feature in the generation of patterned input to the cerebellum.
Abstract  The inferior olivary nucleus (IO) in in vitro slices from postnatal mice (P5.5–P15.5) spontaneously generates clusters of neurons with synchronous calcium transients, and intracellular recordings from IO neurons suggest that electrical coupling between neighbouring IO neurons may serve as a synchronizing mechanism. Here, we studied the cluster‐forming mechanism and find that clusters overlap extensively with an overlap distribution that resembles the distribution for a random overlap model. The average somatodendritic field size of single curly IO neurons was ∼6400 μm2, which is slightly smaller than the average IO cluster size. Eighty‐seven neurons with overlapping dendrites were estimated to be contained in the principal olive mean cluster size, and about six non‐overlapping curly IO neurons could be contained within the largest clusters. Clusters could also be induced by iontophoresis with glutamate. Induced clusters were inhibited by tetrodotoxin, carbenoxelone and 18β‐glycyrrhetinic acid, suggesting that sodium action potentials and electrical coupling are involved in glutamate‐induced cluster formation, which could also be induced by activation of N‐methyl‐d‐aspartate and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors. Spikelets and a small transient depolarizing response were observed during glutamate‐induced cluster formation. Calcium transients spread with decreasing velocity during cluster formation, and somatic action potentials and cluster formation are accompanied by large dendritic calcium transients. In conclusion, cluster formation depends on gap junctions, sodium action potentials and spontaneous clusters occur randomly throughout the IO. The relative slow signal spread during cluster formation, combined with a strong dendritic influx of calcium, may signify that active dendritic properties contribute to cluster formation.
Biological Evaluation of Benzothiazole Ethyl Urea Inhibitors of Bacterial Type II Topoisomerases
Authors: Stokes Neil R. , Thomaides-Brears Helena B. , Barker Stephanie , Bennett James M. , Berry Joanne , Collins Ian , Czaplewski Lloyd G. , Gamble Vicki , Lancett Paul , Logan Alastair , Lunniss Christopher J. , Peasley Hilary , Pommier Stéphanie , Price Daniel , Smee Carol , Haydon David J. 
Published: September 2013

ABSTRACT

The type II topoisomerases DNA gyrase (GyrA/GyrB) and topoisomerase IV (ParC/ParE) are well-validated targets for antibacterial drug discovery. Because of their structural and functional homology, these enzymes are amenable to dual targeting by a single ligand. In this study, two novel benzothiazole ethyl urea-based small molecules, designated compound A and compound B, were evaluated for their biochemical, antibacterial, and pharmacokinetic properties. The two compounds inhibited the ATPase activity of GyrB and ParE with 50% inhibitory concentrations of <0.1 μg/ml. Prevention of DNA supercoiling by DNA gyrase was also observed. Both compounds potently inhibited the growth of a range of bacterial organisms, including staphylococci, streptococci, enterococci,
Clostridium difficile
, and selected Gram-negative respiratory pathogens. MIC
90
s against clinical isolates ranged from 0.015 μg/ml for
Streptococcus pneumoniae
to 0.25 μg/ml for
Staphylococcus aureus
. No cross-resistance with common drug resistance phenotypes was observed. In addition, no synergistic or antagonistic interactions between compound A or compound B and other antibiotics, including the topoisomerase inhibitors novobiocin and levofloxacin, were detected in checkerboard experiments. The frequencies of spontaneous resistance for
S. aureus
were <2.3 × 10
−10
with compound A and <5.8 × 10
−11
with compound B at concentrations equivalent to 8× the MICs. These values indicate a multitargeting mechanism of action. The pharmacokinetic properties of both compounds were profiled in rats. Following intravenous administration, compound B showed approximately 3-fold improvement over compound A in terms of both clearance and the area under the concentration-time curve. The measured oral bioavailability of compound B was 47.7%.
Thioridazine Pharmacokinetic-Pharmacodynamic Parameters “Wobble” during Treatment of Tuberculosis: a Theoretical Basis for Shorter-Duration Curative Monotherapy with Congeners
Authors: Musuka Sandirai , Srivastava Shashikant , Siyambalapitiyage Dona Chandima Wasana , Meek Claudia , Leff Richard , Pasipanodya Jotam , Gumbo Tawanda 
Published: September 2013

ABSTRACT

Phenothiazines are being repurposed for treatment of tuberculosis. We examined time-kill curves of thioridazine and first-line drugs against log-growth-phase and semidormant bacilli under acidic conditions and nonreplicating persistent
Mycobacterium tuberculosis
. While both the potency and the efficacy of first-line drugs declined dramatically as
M. tuberculosis
replication rates decreased, those of thioridazine improved. The mutation prevalence to 3 times the thioridazine MIC was <1 × 10
−11
, better than for ≥2 first-line drugs combined. Hollow fiber system studies revealed that the relationship between sterilizing effect and pharmacodynamic indices (PDI) was characterized by an
r
2
of 0.88 for peak/MIC, an
r
2
of 0.47 for the area under the concentration-time curve (AUC) to MIC, and an
r
2
of 0.14 for the cumulative percentage of a 24-h period that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (%
T
MIC
) at the end of the first week. However, the PDI linked to effect “wobbled” as the duration of therapy increased, so that by the fourth week the
r
2
was 0.88 for AUC/MIC, 0.78 for %T
MIC
, and 0.72 for peak/MIC. This “wobble” has implications on general pharmacokinetic/pharmacodynamic theory, whereby efficacy is linked to only one of the three PDIs in deterministic models. The potency changed 8.9-fold from the first to the fourth weeks. The non-protein-bound AUC/MIC associated with maximal kill at the end of therapy was 50.53 (protein binding = 99.5%). This thioridazine exposure was calculated to extinguish all three
M. tuberculosis
metabolic populations in human lungs in only 42.9 days of monotherapy. However, this concentration exceeds the 2- to 8-mg/liter thioridazine concentration in serum known to be lethal to humans. Therefore, the way forward for phenothiazine monotherapy that also reduces therapy duration is via synthesis of less toxic congeners.
In Vitro
Susceptibility of Aspergillus fumigatus to Isavuconazole: Correlation with Itraconazole, Voriconazole, and Posaconazole
Authors: Gregson Lea , Goodwin Joanne , Johnson Adam , McEntee Laura , Moore Caroline B. , Richardson Malcolm , Hope William W. , Howard Susan J. 
Published: September 2013

ABSTRACT

Triazoles are first-line agents for treating aspergillosis. The prevalence of azole resistance in
Aspergillus fumigatus
is increasing, and cross-resistance is a growing concern. In this study, the susceptibilities of 40
A. fumigatus
clinical isolates were tested by using the CLSI method with amphotericin B, itraconazole, voriconazole, posaconazole, and the new triazole isavuconazole. Isavuconazole MICs were higher in strains with reduced susceptibilities to other triazoles, mirroring changes in voriconazole susceptibility. Isavuconazole MICs differed depending on the Cyp51A substitution.
Impacts of Labile Organic Carbon Concentration on Organic and Inorganic Nitrogen Utilization by a Stream Biofilm Bacterial Community
Authors: Ghosh Suchismita , Leff Laura G. 
Published: September 2013

ABSTRACT
In aquatic ecosystems, carbon (C) availability strongly influences nitrogen (N) dynamics. One manifestation of this linkage is the importance in the dissolved organic matter (DOM) pool of dissolved organic nitrogen (DON), which can serve as both a C and an N source, yet our knowledge of how specific properties of DOM influence N dynamics are limited. To empirically examine the impact of labile DOM on the responses of bacteria to DON and dissolved inorganic nitrogen (DIN), bacterial abundance and community composition were examined in controlled laboratory microcosms subjected to various combinations of dissolved organic carbon (DOC), DON, and DIN treatments. Bacterial communities that had colonized glass beads incubated in a stream were treated with various glucose concentrations and combinations of inorganic and organic N (derived from algal exudate, bacterial protein, and humic matter). The results revealed a strong influence of C availability on bacterial utilization of DON and DIN, with preferential uptake of DON under low C concentrations. Bacterial DON uptake was affected by the concentration and by its chemical nature (labile versus recalcitrant). Labile organic N sources (algal exudate and bacterial protein) were utilized equally well as DIN as an N source, but this was not the case for the recalcitrant humic matter DON treatment. Clear differences in bacterial community composition among treatments were observed based on terminal restriction fragment length polymorphisms (T-RFLP) of 16S rRNA genes. C, DIN, and DON treatments likely drove changes in bacterial community composition that in turn affected the rates of DON and DIN utilization under various C concentrations.
Characteristics of Cefotaxime-Resistant Escherichia coli from Wild Birds in The Netherlands
Authors: Veldman Kees , van Tulden Peter , Kant Arie , Testerink Joop , Mevius Dik 
Published: September 2013

ABSTRACT

Cloacal swabs from carcasses of Dutch wild birds obtained in 2010 and 2011 were selectively cultured on media with cefotaxime to screen for the presence of extended-spectrum β-lactamase (ESBL)/AmpC-producing
Escherichia coli
. Subsequently, all cefotaxime-resistant
E. coli
isolates were tested by broth microdilution and microarray. The presence of ESBL/AmpC and coexisting plasmid-mediated quinolone resistance (PMQR) genes was confirmed by PCR and sequencing. To determine the size of plasmids and the location of ESBL and PMQR genes, S1 pulsed-field gel electrophoresis (PFGE) was performed on transformants, followed by Southern blot hybridization. The study included 414 cloacal swabs originating from 55 different bird species. Cefotaxime-resistant
E. coli
isolates were identified in 65 birds (15.7%) from 21 different species. In all, 65 cefotaxime-resistant
E. coli
ESBL/AmpC genes were detected, mainly comprising variants of
bla
CTX-M
and
bla
CMY-2
. Furthermore, PMQR genes [
aac(6
′
)-lb-cr
,
qnrB1
, and
qnrS1
] coincided in seven cefotaxime-resistant
E. coli
isolates. Overall, replicon typing of the ESBL/AmpC-carrying plasmids demonstrated the predominant presence of IncI1 (
n
= 31) and variants of IncF (
n
= 18). Our results indicate a wide dissemination of ESBL and AmpC genes in wild birds from The Netherlands, especially among aquatic-associated species (waterfowl, gulls, and waders). The identified genes and plasmids reflect the genes found predominantly in livestock animals as well as in humans.