bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic and magnetoresistance behaviors of particulate iron/vinyl ester resin nanocomposites
Authors: Guo Zhanhu , Hahn H. Thomas , Lin Hongfei , Karki Amar B. , Young David P.
Published: July 2008

Magnetoresistance (MR) behavior of vinyl ester monomer stabilized iron nanoparticles and heat-treated vinyl ester resin nanocomposites reinforced with iron nanoparticles were investigated. Vinyl ester monomer serves as a coupling agent with one side covalently bound onto the nanoparticle surface by a displacement reaction and the other end copolymerized with extra vinyl ester resin to form a robust entity. The particle loading and type of material (polymer or carbonized polymer) have a significant effect on the magnetic and MR properties. The heat-treated nanocomposites follow a tunneling conduction. After reduction annealing, the obtained nanocomposites possess a room temperature MR of 8.3 % at a field of 90 kOe.
Method to measure spatial coherence of subangstrom electron beams
Authors: Dwyer Christian , Erni Rolf , Etheridge Joanne
Published: July 2008

A method is described for measuring the intensity distribution of the electron source in a scanning transmission electron microscope (STEM) fitted with an objective lens aberration corrector. The method is applied to a Cs-corrected 300kV field emission gun TEM/STEM, which is found to have an effective source size of 0.56Å full width at half maximum (FWHM) under optical conditions suitable for high resolution STEM imaging. This corresponds to a probe intensity distribution at the specimen plane of 0.72Å FWHM using a probe-forming aperture of 25mrad and including the measured residual lens aberrations.
Modelling European Regional Scenarios: Aggressive versus Defensive Competitive Strategies
Authors: Capello Roberta , Fratesi Ugo
Published: July 2008

The aim of the paper is to tackle the question of what the European territory will look like over the next fifteen years by providing quali–quantitative territorial scenarios for an enlarged Europe, under different assumptions about the future direction in which the driving forces affecting development will move. Based on an econometric model, called MASST, two scenarios are built on the bases of alternative strategies put in place by the EU 15, the New 12, and the BRIC (Brazil, Russia, India, and China) countries, on which alternative behavioural patterns in the driving forces of change depend. The scenarios presented are not policy scenarios: a more general approach is chosen, and more general issues of external competitiveness and global confrontation are emphasised and placed in the forefront of reflection, in an endeavour to define, through the use of the MASST simulation model, their likely impact on territorial trends, regional convergence, and general economic performance. Major determinants of territorial trends are attributed to the competitive game between the three above-mentioned blocks of countries. The model is able to provide the simulations for twenty-seven countries (the ‘Old 15’ EU members and the ‘New 12’ Eastern EU members) and for their 259 regions of GDP and population in 2015 in the two scenarios.
Street Centrality and Densities of Retail and Services in Bologna, Italy
Authors: Porta Sergio , Strano Emanuele , Iacoviello Valentino , Messora Roberto , Latora Vito , Cardillo Alessio , Wang Fahui , Scellato Salvatore
Published: July 2008

This paper examines the relationship between street centrality and densities of commercial and service activities in the city of Bologna, northern Italy. Street centrality is calibrated in a multiple centrality assessment model composed of multiple measures such as closeness, betweenness, and straightness. Kernel density estimation is used to transform datasets of centrality and activities to one scale unit for analysis of correlation between them. Results indicate that retail and service activities in Bologna tend to concentrate in areas with better centralities. The distribution of these activities correlates highly with the global betweenness of the street network, and also, to a slightly lesser extent, with the global closeness. This confirms the hypothesis that street centrality plays a crucial role in shaping the formation of urban structure and land uses.
Effect of timing of forage conservation on forage yield and quality, seed yield and seedling regeneration of four subterranean clover (Trifolium subterraneum) cultivars
Authors: Dear B. S. , Hackney B. F. , Dyce G. M. , Rodham C. A.
Published: July 2008

Swards of four cultivars of subterranean clover (Trifolium subterraneum L.) were cut at three different times to determine the effect on forage yield and quality, seed set and seedling regeneration in two successive seasons in southern New South Wales. The four cultivars of subterranean clover (Seaton Park LF, Junee, Goulburn and Clare) were cut on 23–25 September (early cut), 8–10 October (mid cut) or 22–23 October (late cut), to simulate an early silage, late silage or hay cut. Additional treatments imposed included either grazing or leaving the regrowth after cutting and raising the cutting height from 3 to 6 cm.
Forage yields ranged from 3.5 to 9.3 t dry matter (DM)/ha in the first year and from 2.0 to 5.9 t DM/ha in the second year. Herbage yield was influenced by both cultivar and harvest time with the highest yields achieved with the mid cut. Lower forage yields at the later cut were attributed to losses due to respiration and decay under dense leaf canopies.
Changes in forage quality were consistent across both years, with in vivo DM digestibility declining from 76–79% to 69–70% as cutting time was delayed. Crude protein fell from 22–24% to 14–17% over the same period, depending on cultivar.
Seed yields in both years were influenced by both cutting time and cultivar with a positive relationship (R2 = 0.45–0.61) between herbage present in late spring after a period of regrowth and subsequent seed yield. The early flowering cultivar Seaton Park LF had the highest seed yield in both years and the more erect cultivar Clare had the lowest. Seed yields declined with later cutting time but increased by an average of 39% when the cutting height was raised from 3 to 6 cm. Seedling regeneration reflected seed yield responses with the largest seedling regeneration occurring in treatments cut early.
The study found that forage conservation in early October is likely to yield more and be of higher quality than swards cut later in the season. Seed set is greatly reduced by all cutting strategies to levels unprofitable for seed harvesting but may be adequate for pasture regeneration.
Effectiveness of spring spraying targeting diapause egg production for controlling redlegged earth mites and other pests in pasture
Authors: Gower Jane M. C. , Hoffmann Ary A. , Weeks Andrew R.
Published: July 2008

Earth mites are a complex of related species introduced into Australia in the early part of last century that cause economic damage to crops, especially canola, and to pastures. A general method of chemical control aimed at interrupting the life cycle at the most effective stage, by spraying in the spring before the mites enter diapause, has recently been adopted for controlling earth mites, particularly the redlegged earth mite Halotydeus destructor (Tucker). Here we use paired-paddock treatments and field enclosures to test the effectiveness of this method on pest populations of H. destructor as well as on other pests over two seasons at multiple pasture sites in Victoria. Halotydeus destructor numbers at the start of the winter growing season were suppressed by up to 85%, but this control level was not sustained. The numbers of H. destructor and other pests were similar to or higher than those in the unsprayed areas by spring. Spring spraying is, therefore, a useful means of suppressing H. destructor in early autumn, but its effects disappear relatively quickly over time in Victoria. This strategy also has little impact on the control of the blue oat mite Penthaleus major (Duges) and other phytophagous invertebrate pests.
Emerging pest mites of grains (Balaustium medicagoense and Bryobia sp.) show high levels of tolerance to currently registered pesticides
Authors: Arthur Aston L. , Hoffmann Ary A. , Umina Paul A. , Weeks Andrew R.
Published: July 2008

Balaustium medicagoense and Bryobia sp. (clover or pasture mite) have recently been identified as potential emerging pests of crops and pastures within southern Australia. Recorded damage by these mites has markedly increased in the past decade. There is limited information on the pesticide tolerance of these mites relative to other earth mite pests. This study examined the response of Ba. medicagoense and Bryobia sp., using the redlegged earth mite [Halotydeus destructor (Tucker)] as a comparison, to several currently registered pesticides against earth mites (omethoate, bifenthrin, chlorpyrifos, methidathion and α-cypermethrin). Ba. medicagoense had a much greater level of tolerance to all pesticides tested than H. destructor. Similarly, Bryobia sp. had a higher level of tolerance to bifenthrin, methidathion and α-cypermethrin than H. destructor. However, in the case of omethoate and chlorpyrifos, the tolerance levels were similar for Bryobia sp. and H. destructor. Ba. medicagoense had a higher level of tolerance than Bryobia sp. to the organophosphates tested (omethoate, chlorpyrifos and methidathion), but there was no difference for bifenthrin. We were unable to compare tolerance levels between Ba. medicagoense and Bryobia sp. to α-cypermethrin because of inconsistencies between replicate tests. These emerging pest mite species, therefore, have a high natural tolerance to currently registered pesticides and may prove difficult to control in the field. These findings suggest that other strategies that are not reliant on chemicals should be considered for the control of Ba. medicagoense and Bryobia sp.
Seasonal variation in the concentrations of conjugated linoleic and trans fatty acids in milk fat from commercial dairy farms is associated with pasture and grazing management and supplementary feeding practices
Authors: Dunshea F. R. , Walker G. P. , Ostrowska E. , Doyle P. T.
Published: July 2008

A study of irrigated pasture-based dairy farms that used split calving (autumn and spring) was undertaken in northern Victoria, Australia, to examine associations between nutrition, time of year and season of calving on the concentrations of isomers of trans 18  :  1 fatty acids and conjugated linoleic acids (CLA) in milk fat. Factors associated with time of year explained most of the variation, with the highest concentrations observed in spring and summer when pasture intake by herds was high. However, there was substantial variation observed between herds and time of year. The mean total CLA concentration was 9.1 mg/g milk fatty acids (range 1.1–35.4 mg/g) with the cis,trans-9,11 accounting for ~84% of the total CLA. The mean total trans 18 : 1 concentration was 60.5 mg/g milk fatty acids (range 13.6–267 mg/g) with vaccenic acid (trans-11 18 : 1) accounting for ~53% of total trans 18 : 1 fatty acids. Total CLA and vaccenic acid were highest in August–September (southern hemisphere spring) (15.1 and 76.3 mg/g milk fat) and lowest in November–March (5.6 mg/g milk fat) and May–July (9.53 mg/g milk fat), respectively. There was no association between season of calving and milk CLA or trans 18 : 1 fatty acid concentrations. Trans-10 and -11 18 : 1 fatty acids and trans/trans-CLA were negatively correlated with milk fat concentrations. Management strategies designed to increase the concentration of CLA and trans 18 : 1 fatty acids in milk fat would not need to consider the effects of season of calving or stage of lactation, but should focus on pasture availability and quality.
Reducing the lysine to energy content in the grower growth phase diet increases intramuscular fat and improves the eating quality of the longissimus thoracis muscle of gilts
Authors: D'Souza D. N. , Pethick D. W. , Dunshea F. R. , Pluske J. R. , Mullan B. P.
Published: July 2008

Sixty-three (Large White × Landrace × Duroc) female finisher pigs were used to determine the effect of nutritional manipulations on growth performance, carcass quality and sensory pork quality. The dietary treatments were: (i) control [pigs fed a commercial grower (73–125 days of age) and finisher diet (126–163 days of age)]; (ii) 15% reduced lysine : energy diet during the grower phase followed by a commercial finisher diet; and (iii) pigs fed the control diet with no supplemented vitamin A in the mineral–vitamin premix during both the grower and finisher phases. Pigs fed the reduced lysine diet had higher (P < 0.05) intramuscular fat levels compared with pigs fed the control and the vitamin A- restricted diets. The pork from pigs fed the reduced lysine diet had a lower ultimate muscle pH, was paler (higher L*) and had a higher b* value (yellowness-blueness) compared with pork from the control pigs (all P < 0.05). Pork from pigs fed the reduced lysine diet was considered to be the most juicy and tender and have the best overall acceptability (all P < 0.05), followed by pork from pigs fed the control and vitamin A-restricted diets. In conclusion, feeding pigs a 15% reduced lysine : energy diet significantly increased intramuscular fat levels and improved the sensory quality of pork.
Designing complex research projects to estimate genetic parameters plus treatment and other effects - optimising the experimental design
Authors: Robinson D. L.
Published: July 2008

There is an increasing trend towards integrated research, in which several individuals or institutions pool their expertise and make use of common resources, collaborating towards a common set of scientific goals. Integrated research enables a larger number of factors to be investigated, and the most influential or important ones identified, providing information on how the different factors interact or fit together. Good experimental design is, however, required to ensure the aims can be achieved and resources spent wisely.
Issues involved in the experimental design of the Australian Beef Cattle Cooperative Research Centre for Meat Quality are discussed. Theoretical results and simulation studies were used to determine optimal numbers of progeny per sire for estimating genetic parameters. For heritabilities of 0.2 and 0.5, the optima are respectively 21 and 9 progeny with recorded measurements. The curves surrounding the optima are quite flat, so aiming for 10–15 progeny with measurements per trait should provide reasonable accuracy in many situations. Estimates of heritabilities, genetic correlations and phenotypic variances have lower sampling correlations than genetic variances and covariances, suggesting that when results are pooled over different breeds or trials, it is better to pool estimates of heritabilities and genetic correlations than (co)variances.
Using sires in more than one year increases the robustness of estimated sire effects and increases the accuracy of genetic parameter estimates for hard-to-measure traits (e.g. feed efficiency) that are not recorded on all animals. Unless sires can be chosen as a true random sample of the population, arrangements of link sires (and other effects such as treatments) should be chosen to provide accurate estimates when all terms in the model are fitted as fixed.
Dissection of beef quality phenotypes using a myogenin network-anchored systems biology approach
Authors: Reverter A. , Chan E. K. F. , Lehnert S. A. , Barris W. , McWilliam S. M. , Dalrymple B. P. , Barendse W.
Published: July 2008

In order to uncover genes with transcriptional activity linked to various beef quality phenotypes of interest, we designed a systems biology approach. We focussed on traits representing the three major categories of growth and development, fat depots and meat quality phenotypes. We proceeded by linking bovine gene expression data derived from 147 microarray hybridisation experiments and high density marker data from 9260 single nucleotide polymorphisms (SNP) on 189 steers. The individuals in the genotyping study were unrelated to the samples used for expression profiling. The linkage was performed by anchoring these data to a gene network for myogenin (MYOG), a muscle-specific transcription factor essential for the development of skeletal muscle. This approach was able to identify and estimate the strength of the relationship between the statistical association of a SNP to a phenotype of interest with the transcriptional activity of genes in the network. The genes from the MYOG-centred network that were significantly associated with the largest number of meat quality traits were PDLIM3, CALM1 and CRYAB. Among our findings, a novel association between desmin and meat colour points to an alternative biochemical basis for meat colour differences involving costameric structures and their previously reported relationship with tenderness. These newly generated hypotheses can help formulate sound research to further illuminate the genetic architecture of beef quality phenotypes.
Ewe lamb nutrition during pregnancy affects pregnancy outcome
Authors: Mulvaney F. J. , Kenyon P. R. , Morris S. T. , West D. M.
Published: July 2008

This experiment aimed to investigate the impact of pregnancy nutritional treatment on ewe lamb pregnancy rate and pregnancy loss and the liveweight of resulting lambs. Two hundred and forty ewe lambs mated during a 5-day breeding period were randomly allocated to one of three nutritional regimes (‘low’, ‘medium’ and ‘high’). The low (n = 80) treatment group was fed pasture to maintain liveweight during the first 100 days of pregnancy, thereafter feeding was increased to achieve a total liveweight change of 180 g/day. The medium treatment group was fed to ensure a liveweight change equivalent to 100 g/day throughout the entire pregnancy period, while the high treatment group was offered feed ab libitum.
The target liveweight changes were achieved in all ewe lamb treatment groups. Fewer (P < 0.05) ewe lambs were scanned pregnant at day 50 of pregnancy and lambed in the high treatment compared with their medium counterparts. In addition, fewer (P < 0.05) low treatment ewe lambs lambed compared with the medium treatment ewe lambs. The lower numbers lambing in the low and high treatment groups were somewhat explained by greater (P < 0.05) pregnancy losses between day 50 and term. Lambs born to low treatment ewe lambs were lighter (P < 0.05) at birth (L0), L53 and L87 and had lower (P < 0.05) survival rates than those born to either medium or high treatment ewe lambs.
While the present study was not designed to identify optimal ewe lamb feeding levels in pregnancy, it clearly indicates adverse effects from either a low or high level of pregnancy nutrition beginning in early pregnancy. Therefore, further studies are required to identify the optimal pastoral feeding conditions for the pregnant ewe lamb.
The maternal-effect, selfish genetic element
Medea
is associated with a composite
Tc1
transposon
Authors: Lorenzen Marcé D. , Gnirke Andreas , Margolis Jonathan , Garnes Jeffrey , Campbell Margie , Stuart Jeffrey J. , Aggarwal Rajat , Richards Stephen , Park Yoonseong , Beeman Richard W.
Published: July 2008

Maternal-Effect Dominant Embryonic Arrest
(“
Medea
”) factors are selfish nuclear elements that combine maternal-lethal and zygotic-rescue activities to gain a postzygotic survival advantage. We show that
Medea

1

activity in
Tribolium castaneum
is associated with a composite
Tc1
transposon inserted just downstream of the neurotransmitter reuptake symporter
bloated tubules
(
blot
), whose
Drosophila
ortholog has both maternal and zygotic functions. The 21.5-kb insertion contains defective copies of
elongation initiation factor-3
,
ATP synthase subunit C
, and an
RNaseD
-related gene, as well as a potentially intact copy of a prokaryotic
DUF1703
gene. Sequence comparisons suggest that the current distribution of
Medea

1

reflects global emanation after a single transpositional event in recent evolutionary time. The
Medea
system in
Tribolium
represents an unusual type of intragenomic conflict and could provide a useful vehicle for driving desirable genes into populations.
A Cre-loxP-based mouse model for conditional somatic gene expression and knockdown
in vivo
by using avian retroviral vectors
Authors: Seidler Barbara , Schmidt Annegret , Mayr Ulrich , Nakhai Hassan , Schmid Roland M. , Schneider Günter , Saur Dieter
Published: July 2008

Site- and time-specific somatic gene transfer by using the avian sarcoma-leukosis retrovirus RCAS (replication-competent avian sarcoma-leukosis virus long terminal repeat with splice acceptor) has been shown to be a powerful tool to analyze gene function
in vivo
. RCAS retroviruses that express the avian subgroup A envelope transduce only mammalian cells genetically engineered to express the avian retroviral receptor, tumor virus A (TVA). Here, we generated a knockin mouse line termed

LSL-R26
Tva-lacZ

with concomitant conditional expression of TVA and lacZ by targeting the
Rosa26
locus. A loxP-flanked transcriptional stop cassette was used for conditional activation of TVA and LacZ expression in a Cre-recombinase-dependent manner. To demonstrate the ability of this system for conditional somatic gene transfer
in vivo
, we directed TVA expression to the pancreas. Introduction of an RCAS vector with Bryan-RSV polymerase and subgroup A envelope [RCASBP(A)] carrying oncogenic

Kras
G12D

induced focal ductal pancreatic lesions that recapitulate human pancreatic intraepithelial neoplasias that progress to pancreatic ductal adenocarcinomas. TVA-mediated infection of genetically engineered mice with endogenous expression of Kras
G12D
in pancreatic progenitor cells by using RCASBP(A) virus carrying a short hairpin RNA directed against murine TP53, resulted in dramatically enhanced progression to invasive adenocarcinomas. These results show that conditional expression of TVA enables spatiotemporal gene expression and knockdown in a small subset of somatic cells
in vivo
. Therefore, it closely models carcinogenesis in humans where tumors evolve from somatic gene mutations in developmentally normal cells. Combined with the growing number of Cre expression models, RCAS-TVA-based gene expression and knockdown systems open up promising perspectives for analysis of gene function in a time-controlled and tissue-specific fashion
in vitro
and
in vivo
.
Flavin-dependent thymidylate synthase X limits chromosomal DNA replication
Authors: Escartin Frédéric , Skouloubris Stéphane , Liebl Ursula , Myllykallio Hannu
Published: July 2008

We have investigated the hitherto unexplored possibility that differences in the catalytic efficiencies of thymidylate synthases ThyX and ThyA, enzymes that produce the essential DNA precursor dTMP, have influenced prokaryotic genome evolution. We demonstrate that DNA replication speed in bacteria and archaea that contain the low-activity ThyX enzyme is up to 10-fold decreased compared with species that contain the catalytically more efficient ThyA. Our statistical studies of >400 genomes indicated that ThyA proteins are preferred for the replication of large genomes, providing further evidence that the thymidylate metabolism is limiting expansion of prokaryotic genomes. Because both ThyX and ThyA participate in frequent reciprocal gene replacement events, our observations indicate that the bacterial metabolism continues to modulate the size and composition of prokaryotic genomes. We also propose that the increased kinetic efficiency of thymidylate synthesis has contributed to extending the prokaryotic evolutionary potential.
Fine-scale mapping of recombination rate in
Drosophila
refines its correlation to diversity and divergence
Authors: Kulathinal Rob J. , Bennett Sarah M. , Fitzpatrick Courtney L. , Noor Mohamed A. F.
Published: July 2008

Regional rates of recombination often correlate with levels of nucleotide diversity, and either selective or neutral hypotheses can explain this relationship. Regional recombination rates also correlate with nucleotide differences between human and chimpanzee, consistent with models where recombination is mutagenic; however, a lack of correlation is observed in the
Drosophila melanogaster
group, consistent with models invoking natural selection. Here, we revisit the relationship among recombination, diversity, and interspecies difference by generating empirical estimates of these parameters in
Drosophila pseudoobscura
. To measure recombination rate, we genotyped 1,294 backcross hybrids at 50 markers across the largest assembled linkage group in this species. Genome-wide diversity was estimated by sequencing a second isolate of
D. pseudoobscura
at shallow coverage. Alignment to the sequenced genome of the closely related species,
Drosophila persimilis
, provided nucleotide site orthology. Our findings demonstrate that scale is critical in determining correlates to recombination rate: fine-scale cross-over rate estimates are far stronger predictors of both diversity and interspecies difference than broad-scale estimates. The correlation of fine-scale recombination rate to diversity and interspecies difference appears to be genome-wide, evidenced by examination of an X-linked region in greater detail. Because we observe a strong correlation of cross-over rate with interspecies difference, even after correcting for segregating ancestral variation, we suggest that both mutagenic and selective forces generate these correlations, the latter in regions of low crossing over. We propose that it is not cross-overs
per se
that are mutagenic, but rather repair of DNA double-strand break precursors via crossing over and gene conversion.
FOXC2 controls Ang-2 expression and modulates angiogenesis, vascular patterning, remodeling, and functions in adipose tissue
Authors: Xue Yuan , Cao Renhai , Nilsson Daniel , Chen Shaohua , Westergren Rickard , Hedlund Eva-Maria , Martijn Cecile , Rondahl Lena , Krauli Per , Walum Erik , Enerbäck Sven , Cao Yihai
Published: July 2008

Adipogenesis is spatiotemporally coupled to angiogenesis throughout adult life, and the interplay between these two processes is communicated by multiple factors. Here we show that in a transgenic mouse model, increased expression of forkhead box C2 (FOXC2) in the adipose tissue affects angiogenesis, vascular patterning, and functions. White and brown adipose tissues contain a considerably high density of microvessels appearing as vascular plexuses, which show redistribution of vascular smooth muscle cells and pericytes. Dysfunction of these primitive vessels is reflected by impairment of skin wound healing. We further provide a mechanistic insight of the vascular phenotype by showing that FOXC2 controls Ang-2 expression by direct activation of its promoter in adipocytes. Remarkably, an Ang-2-specific antagonist almost completely reverses this vascular phenotype. Thus, the FOXC2–Ang-2 signaling system is crucial for controlling adipose vascular function, which is part of an adaptation to increased adipose tissue metabolism.
In silico
identified CCR4 antagonists target regulatory T cells and exert adjuvant activity in vaccination
Authors: Bayry Jagadeesh , Tchilian Elma Z. , Davies Matthew N. , Forbes Emily K. , Draper Simon J. , Kaveri Srini V. , Hill Adrian V. S. , Kazatchkine Michel D. , Beverley Peter C. L. , Flower Darren R. , Tough David F.
Published: July 2008

Adjuvants are substances that enhance immune responses and thus improve the efficacy of vaccination. Few adjuvants are available for use in humans, and the one that is most commonly used (alum) often induces suboptimal immunity for protection against many pathogens. There is thus an obvious need to develop new and improved adjuvants. We have therefore taken an approach to adjuvant discovery that uses
in silico
modeling and structure-based drug-design. As proof-of-principle we chose to target the interaction of the chemokines CCL22 and CCL17 with their receptor CCR4. CCR4 was posited as an adjuvant target based on its expression on CD4
+
CD25
+
regulatory T cells (Tregs), which negatively regulate immune responses induced by dendritic cells (DC), whereas CCL17 and CCL22 are chemotactic agents produced by DC, which are crucial in promoting contact between DC and CCR4
+
T cells. Molecules identified by virtual screening and molecular docking as CCR4 antagonists were able to block CCL22- and CCL17-mediated recruitment of human Tregs and Th2 cells. Furthermore, CCR4 antagonists enhanced DC-mediated human CD4
+
T cell proliferation in an
in vitro
immune response model and amplified cellular and humoral immune responses
in vivo
in experimental models when injected in combination with either Modified Vaccinia Ankara expressing Ag85A from
Mycobacterium tuberculosis
(MVA85A) or recombinant hepatitis B virus surface antigen (rHBsAg) vaccines. The significant adjuvant activity observed provides good evidence supporting our hypothesis that CCR4 is a viable target for rational adjuvant design.
Amide bonds assemble pili on the surface of bacilli
Authors: Budzik Jonathan M. , Marraffini Luciano A. , Souda Puneet , Whitelegge Julian P. , Faull Kym F. , Schneewind Olaf
Published: July 2008

Pilin precursors are the building blocks of pili on the surface of Gram-positive bacteria; however, the assembly mechanisms of these adhesive fibers are unknown. Here, we describe the chemical bonds that assemble BcpA pilin subunits on the surface ofBacillus cereus. Sortase D cleaves BcpA precursor between the threonine (T) and the glycine (G) residues of its LPXTG sorting signal and catalyzes formation of an amide bond between threonine (T) of the sorting signal and lysine (K) in the YPKN motif of another BcpA subunit. Three CNA B domains of BcpA generate intramolecular amide bonds, and one of these contributes also to pilus formation. Conservation of catalysts and structural elements in pilin precursors in Gram-positive bacteria suggests a universal mechanism of fiber assembly.
Distinct conformational changes in β-arrestin report biased agonism at seven-transmembrane receptors
Authors: Shukla Arun K. , Violin Jonathan D. , Whalen Erin J. , Gesty-Palmer Diane , Shenoy Sudha K. , Lefkowitz Robert J.
Published: July 2008

β-arrestins critically regulate G protein-coupled receptors (GPCRs), also known as seven-transmembrane receptors (7TMRs), both by inhibiting classical G protein signaling and by initiating distinct β-arrestin-mediated signaling. The recent discovery of β-arrestin-biased ligands and receptor mutants has allowed characterization of these independent “G protein-mediated” and “β-arrestin-mediated” signaling mechanisms of 7TMRs. However, the molecular mechanisms underlying the dual functions of β-arrestins remain unclear. Here, using an intramolecular BRET (bioluminescence resonance energy transfer)-based biosensor of β-arrestin 2 and a combination of biased ligands and/or biased mutants of three different 7TMRs, we provide evidence that β-arrestin can adopt multiple “active” conformations. Surprisingly, phosphorylation-deficient mutants of the receptors are also capable of directing similar conformational changes in β-arrestin as is the wild-type receptor. This indicates that distinct receptor conformations induced and/or stabilized by different ligands can promote distinct and functionally specific conformations in β-arrestin even in the absence of receptor phosphorylation. Our data thus highlight another interesting aspect of 7TMR signaling—i.e., functionally specific receptor conformations can be translated to downstream effectors such as β-arrestins, thereby governing their functional specificity.
Short Article: Microstructural Analysis of Ingestive Behaviour Reveals no Contribution of Palatability to the Incomplete Extinction of a Conditioned Taste Aversion
Authors: Dwyer Dominic M.
Published: July 2008

An analysis of the microstructure of licking responses was used to investigate the effects of conditioning and extinguishing a taste aversion. Rats received a single pairing of 8% fructose with lithium chloride (LiCl) while controls received unpaired exposure to fructose and LiCl. Pairing fructose with LiCl produced a reduction both in consumption and in the size of licking clusters. Subsequent exposure to fructose in the absence of LiCl produced some extinction of the taste aversion although at asymptote there was a residual difference in consumption between the taste aversion group and unpaired controls. In contrast the reduction in lick cluster size did completely extinguish. Previous analyses of licking microstructure indicate that lick cluster size is related to the palatability of the ingested solution. Thus these results indicate that although taste aversion learning initially reduces the palatability of the cue solution this reduction is not permanent. These results are discussed with reference to the possibility that preparatory behaviours are more resistant to extinction than are consummatory behaviours.
Outbreaks of Influenza A Among Nonvaccinated Healthcare Workers: Implications for Resource-Limited Settings
Authors: Apisarnthanarak Anucha , Puthavathana Pilaipan , Kitphati Rungrueng , Auewarakul Prasert , Mundy Linda M.
Published: July 2008

We identified 3 outbreaks of influenza A (attack rates, 18%–24%) among Thai healthcare workers in intensive care units. All outbreaks were epidemiologically linked to an index patient with pneumonia due to influenza A virus (subtype H3N2). The investigations of these outbreaks incurred costs that exceeded the estimated costs of healthcare worker influenza vaccination by more than 10-fold.
Implementation of an Industrial Systems-Engineering Approach to Reduce the Incidence of Methicillin-ResistantStaphylococcus aureusInfection
Authors: Muder Robert R. , Cunningham Candace , McCray Ellesha , Squier Cheryl , Perreiah Peter , Jain Rajiv , Sinkowitz-Cochran Ronda L. , Jernigan John A.
Published: July 2008

Objective.

To measure the effectiveness of an industrial systems-engineering approach to a methicillin-resistantStaphylococcus aureus(MRSA) prevention program.

Design.

Before-after intervention study

Setting.

An intensive care unit (ICU) and a surgical unit that was not an ICU in the Pittsburgh Veterans Administration hospital

Patients.

Allpatientsadmittedtothe study units

Intervention.

We implemented an MRSA infection control program that consisted of the following 4 elements: (1) the use of standard precautions for all patient contact, with emphasis on hand hygiene; (2) the use of contact precautions for interactions with patients known to be infected or colonized with MRSA; (3) the use of active surveillance cultures to identify patients who were asymptomatically colonized with MRSA; and (4) use of an industrial systems-engineering approach, the Toyota Production System, to facilitate consistent and reliable adherence to the infection control program.

Results.

The rate of healthcare-associated MRSA infection in the surgical unit decreased from 1.56 infections per 1,000 patient-days in the 2 years before the intervention to 0.63 infections per 1,000 patient-days in the 4 years after the intervention (a 60% reduction;P= .003). The rate of healthcare-associated MRSA infection in the ICU decreased from 5.45 infections per 1,000 patient-days in the 2 years before to the intervention to 1.35 infections per 1,000 patient-days in the 3 years after the intervention (a 75% reduction;P= .001). The combined estimate for reduction in the incidence of infection after the intervention in the 2 units was 68% (95% confidence interval, 50%-79%;P< .001).

Conclusions.

Sustained reduction in the incidence of MRSA infection is possible in a setting where this pathogen is endemic. An industrial systems-engineering approach can be adapted to facilitate consistent and reliable adherence to MRSA infection prevention practices in healthcare facilities.
Variation in Mortality Rates Among Long-Term Care Facilities for Residents With Lower Respiratory Tract Infection
Authors: Nicolle L. E. , Mubareka S. , Simor A. , Liu B. , McNeil S. , Lewis D. , Duckworth H. , Cheang M. , Loeb M.
Published: July 2008

Objective.

To identify variables contributing to interfacility differences in mortality among residents of long-term care facilities who have lower respiratory tract infection.

Design.

Multicenter, prospective, 1 -year observational study.

Setting.

Twenty-one long-term care facilities in 4 geographic areas of Canada.

Participants.

Residents of long-term care facilities prescribed antimicrobials for treatment of lower respiratory tract infection.

Methods.

Mortality rates were calculated for 3 definitions of lower respiratory tract infection: episodes with a clinical or radiographic diagnosis and treated with antimicrobials (definition 1); episodes with a physician diagnosis of pneumonia (definition 2); and episodes with chest radiography findings consistent with pneumonia (definition 3). Multilevel modeling was used to evaluate variables describing premorbid resident status, clinical presentation, management, and facility characteristics. Multivariable models were developed to identify independent predictors of mortality and determine whether facility-level variables remained independently associated with mortality rate after incorporation of individual-level variables.

Results.

Facility mortality rates varied from 0% to 17.8% for definition 1, from 0% to 47.1% for definition 2, and from 0% to 37.5% for definition 3. There were significant differences in mortality rate depending on which definition was used; for definitions 1 and 2, there were significant differences in mortality rate across facilities. Poorer premorbid resident status and a more severe presentation remained independent predictors of mortality in the multivariable analysis. There were also significantly increased mortality rates for episodes in which a fluoroquinolone was prescribed for initial treatment. For definitions 1 and 3, facility-level variables remained independently associated with mortality rate in the final multivariable model.

Conclusions.

Rates of mortality due to lower respiratory tract infection varied among long-term care facilities and differed within a facility, depending on the definition applied. Variables describing premorbid resident status, severity of presentation, and management did not fully explain the variation in mortality rate. Some facility-level variables remained independent predictors of mortality.
Classification with reject option in gene expression data
Authors: Hanczar Blaise , Dougherty Edward R.
Published: July 2008

Motivation: The classification methods typically used in bioinformatics classify all examples, even if the classification is ambiguous, for instance, when the example is close to the separating hyperplane in linear classification. For medical applications, it may be better to classify an example only when there is a sufficiently high degree of accuracy, rather than classify all examples with decent accuracy. Moreover, when all examples are classified, the classification rule has no control over the accuracy of the classifier; the algorithm just aims to produce a classifier with the smallest error rate possible. In our approach, we fix the accuracy of the classifier and thereby choose a desired risk of error.

Results: Our method consists of defining a rejection region in the feature space. This region contains the examples for which classification is ambiguous. These are rejected by the classifier. The accuracy of the classifier becomes a user-defined parameter of the classification rule. The task of the classification rule is to minimize the rejection region with the constraint that the error rate of the classifier be bounded by the chosen target error. This approach is also used in the feature-selection step. The results computed on both synthetic and real data show that classifier accuracy is significantly improved.

Availability: Companion Website. http://gsp.tamu.edu/Publications/rejectoption/

Contact:  edward@ece.tamu.edu, hanczar_blaise@yahoo.fr

Supplementary information:  Supplementary data are available at Bioinformatics online.
Integrating metabolic, transcriptional regulatory and signal transduction models inEscherichia coli
Authors: Covert Markus W. , Xiao Nan , Chen Tiffany J. , Karr Jonathan R.
Published: July 2008

Motivation: The effort to build a whole-cell model requires the development of new modeling approaches, and in particular, the integration of models for different types of processes, each of which may be best described using different representation. Flux-balance analysis (FBA) has been useful for large-scale analysis of metabolic networks, and methods have been developed to incorporate transcriptional regulation (regulatory FBA, or rFBA). Of current interest is the integration of these approaches with detailed models based on ordinary differential equations (ODEs).

Results: We developed an approach to modeling the dynamic behavior of metabolic, regulatory and signaling networks by combining FBA with regulatory Boolean logic, and ordinary differential equations. We use this approach (called integrated FBA, or iFBA) to create an integrated model of Escherichia coli which combines a flux-balance-based, central carbon metabolic and transcriptional regulatory model with an ODE-based, detailed model of carbohydrate uptake control. We compare the predicted Escherichia coli wild-type and single gene perturbation phenotypes for diauxic growth on glucose/lactose and glucose/glucose-6-phosphate with that of the individual models. We find that iFBA encapsulates the dynamics of three internal metabolites and three transporters inadequately predicted by rFBA. Furthermore, we find that iFBA predicts different and more accurate phenotypes than the ODE model for 85 of 334 single gene perturbation simulations, as well for the wild-type simulations. We conclude that iFBA is a significant improvement over the individual rFBA and ODE modeling paradigms.

Availability: All MATLAB files used in this study are available at http://www.simtk.org/home/ifba/.

Contact:  covert@stanford.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Disturbed Behaviour and the Mental Health Act
Authors: Kendrick Tony , Simon Chantal
Published: July 2008

When a patient becomes very agitated or violent, threatens suicide or starts to behave oddly, the GP is usually called—by the patient, relatives or friends or police attending the disturbance. As a GP, it is important to know how to handle such situations and under what circumstances the Mental Health Act applies.
Anaphylaxis
Authors: Simon Chantal , O'Reilly Karen
Published: July 2008

Anaphylaxis is a severe, systemic allergic reaction that is life threatening. Although less than 1% of those that suffer an anaphylactic attack die as a result of that attack, in the UK, there are approximately 20 deaths each year from anaphylaxis (one death per 3 million population). Risk of death is increased in those with pre-existing asthma, particularly, if the asthma is poorly controlled. Half of all fatalities due to anaphylaxis result from circulatory collapse (shock) and the remainder from respiratory failure (asphyxia). Prompt recognition and appropriate management saves lives.
Adult Obesity and Diet
Authors: Simon Chantal
Published: July 2008

We are what we eat. Although rather clichéd, the level of fat in the diet of a population does directly mirror the incidence of heart disease and there are many other dietary factors which have both direct and indirect links with disease. For example, excess ingestion of salt is associated with high blood pressure; low roughage diets are associated with bowel cancer; ingestion of infected beef causes Creutzfeldt—Jakob disease; eggs may carry salmonella and some food additives have been associated with hyperactivity.
Minimizing Pseudohyperkalaemia in Blood Samples from General Practice
Authors: Carabine Edward
Published: July 2008

A day in the life of a GP usually begins with the daily trawl through our email inbox to check the results of the blood tests. The assessment of renal function, with U + Es (i.e. urea, creatinine, sodium and potassium), will form a significant percentage of them. Severe hyperkalaemia is a life-threatening emergency as it may cause cardiac arrhythmias, leading to cardiac arrest. With these potentially catastrophic sequelae, urgent investigation and treatment of genuine hyperkalaemia is essential. Common causes of hyperkalaemia include renal failure, metabolic acidosis and drugs (e.g. potassium sparing diuretics, Angiotensin Converting Enzyme (ACE) inhibitors and excess potassium therapy). However, a well recognized cause of raised serum potassium is pseudohyperkalaemia.
Combination of Novel Green Fluorescent Protein Mutant TSapphire and DsRed Variant mOrange to Set Up a Versatile in Planta FRET-FLIM Assay
Authors: Bayle Vincent , Nussaume Laurent , Bhat Riyaz A.
Published: July 2008

Förster resonance energy transfer (FRET) measurements based on fluorescence lifetime imaging microscopy (FLIM) are increasingly being used to assess molecular conformations and associations in living systems. Reduction in the excited-state lifetime of the donor fluorophore in the presence of an appropriately positioned acceptor is taken as strong evidence of FRET. Traditionally, cyan fluorescent protein has been widely used as a donor fluorophore in FRET experiments. However, given its photolabile nature, low quantum yield, and multiexponential lifetime, cyan fluorescent protein is far from an ideal donor in FRET imaging. Here, we report the application and use of the TSapphire mutant of green fluorescent protein as an efficient donor to mOrange in FLIM-based FRET imaging in intact plant cells. Using time-correlated single photon counting-FLIM, we show that TSapphire expressed in living plant cells decays with lifetime of 2.93 ± 0.09 ns. Chimerically linked TSapphire and mOrange (with 16-amino acid linker in between) exhibit substantial energy transfer based on the reduction in the lifetime of TSapphire in the presence of the acceptor mOrange. Experiments performed with various genetically and/or biochemically known interacting plant proteins demonstrate the versatility of the FRET-FLIM system presented here in different subcellular compartments tested (cytosol, nucleus, and at plasma membrane). The better spectral overlap with red monomers, higher photostability, and monoexponential lifetime of TSapphire makes it an ideal FRET-FLIM donor to study protein-protein interactions in diverse eukaryotic systems overcoming, in particular, many technical challenges encountered (like autofluorescence of cell walls and fluorescence of pigments associated with photosynthetic apparatus) while studying plant protein dynamics and interactions.
A Novel RNA-Binding Protein Associated with Cell Plate Formation
Authors: Ma Lian , Xie Bo , Hong Zonglie , Verma Desh Pal S. , Zhang Zhongming
Published: July 2008

Building a cell plate during cytokinesis in plant cells requires the participation of a number of proteins in a multistep process. We previously identified phragmoplastin as a cell plate-specific protein involved in creating a tubulovesicular network at the cell plate. We report here the identification and characterization of a phragmoplastin-interacting protein, PHIP1, in Arabidopsis (Arabidopsis thaliana). It contains multiple functional motifs, including a lysine-rich domain, two RNA recognition motifs, and three CCHC-type zinc fingers. Polypeptides with similar motif structures were found only in plant protein databases, but not in the sequenced prokaryotic, fungal, and animal genomes, suggesting that PHIP1 represents a plant-specific RNA-binding protein. In addition to phragmoplastin, two Arabidopsis small GTP-binding proteins, Rop1 and Ran2, are also found to interact with PHIP1. The zinc fingers of PHIP1 were not required for its interaction with Rop1 and phragmoplastin, but they may participate in its binding with the Ran2 mRNA. Immunofluorescence, in situ RNA hybridization, and green fluorescent protein tagging experiments showed the association of PHIP1 with the forming cell plate during cytokinesis. Taken together, our data suggest that PHIP1 is a novel RNA-binding protein and may play a unique role in the polarized mRNA transport to the vicinity of the cell plate.