bluuebunny/crossref_metadata_2025 huggingface dataset:
Social discrimination by quantitative assessment of immunogenetic similarity
Authors: Villinger Jandouwe , Waldman Bruce
Published: September 2012

Genes of the major histocompatibility complex (MHC) that underlie the adaptive immune system may allow vertebrates to recognize their kin. True kin-recognition genes should produce signalling products to which organisms can respond. Allelic variation in the peptide-binding region (PBR) of MHC molecules determines the pool of peptides that can be presented to trigger an immune response. To examine whether these MHC peptides also might underlie assessments of genetic similarity, we tested whetherXenopus laevistadpoles socially discriminate between pairs of siblings with which they differed in PBR amino acid sequences. We found that tadpoles (four sibships,n= 854) associated preferentially with siblings with which they were more similar in PBR amino acid sequence. Moreover, the strength of their preference for a conspecific was directly proportional to the sequence similarity between them. Discrimination was graded, and correlated more closely with functional sequence differences encoded by MHC class I and class II alleles than with numbers of shared haplotypes. Our results thus suggest that haplotype analyses may fail to reveal fine-scale behavioural responses to divergence in functionally expressed sequences. We conclude that MHC–PBR gene products mediate quantitative social assessment of immunogenetic similarity that may facilitate kin recognition in vertebrates.
Human selection of elk behavioural traits in a landscape of fear
Authors: Ciuti Simone , Muhly Tyler B. , Paton Dale G. , McDevitt Allan D. , Musiani Marco , Boyce Mark S.
Published: September 2012

Among agents of selection that shape phenotypic traits in animals, humans can cause more rapid changes than many natural factors. Studies have focused on human selection of morphological traits, but little is known about human selection of behavioural traits. By monitoring elk (
Cervus elaphus
) with satellite telemetry, we tested whether individuals harvested by hunters adopted less favourable behaviours than elk that survived the hunting season. Among 45 2-year-old males, harvested elk showed bolder behaviour, including higher movement rate and increased use of open areas, compared with surviving elk that showed less conspicuous behaviour. Personality clearly drove this pattern, given that inter-individual differences in movement rate were present before the onset of the hunting season. Elk that were harvested further increased their movement rate when the probability of encountering hunters was high (close to roads, flatter terrain, during the weekend), while elk that survived decreased movements and showed avoidance of open areas. Among 77 females (2–19 y.o.), personality traits were less evident and likely confounded by learning because females decreased their movement rate with increasing age. As with males, hunters typically harvested females with bold behavioural traits. Among less-experienced elk (2–9 y.o.), females that moved faster were harvested, while elk that moved slower and avoided open areas survived. Interestingly, movement rate decreased as age increased in those females that survived, but not in those that were eventually harvested. The latter clearly showed lower plasticity and adaptability to the local environment. All females older than 9 y.o. moved more slowly, avoided open areas and survived. Selection on behavioural traits is an important but often-ignored consequence of human exploitation of wild animals. Human hunting could evoke exploitation-induced evolutionary change, which, in turn, might oppose adaptive responses to natural and sexual selection.
Repeated trans-watershed hybridization among haplochromine cichlids (Cichlidae) was triggered by Neogene landscape evolution
Authors: Schwarzer Julia , Swartz Ernst Roelof , Vreven Emmanuel , Snoeks Jos , Cotterill Fenton Peter David , Misof Bernhard , Schliewen Ulrich Kurt
Published: September 2012

The megadiverse haplochromine cichlid radiations of the East African lakes, famous examples of explosive speciation and adaptive radiation, are according to recent studies, introgressed by different riverine lineages. This study is based on the first comprehensive mitochondrial and nuclear DNA dataset from extensive sampling of riverine haplochromine cichlids. It includes species from the lower River Congo and Angolan (River Kwanza) drainages. Reconstruction of phylogenetic hypotheses revealed the paradox of clearly discordant phylogenetic signals. Closely related mtDNA haplotypes are distributed thousands of kilometres apart and across major African watersheds, whereas some neighbouring species carry drastically divergent mtDNA haplotypes. At shallow and deep phylogenetic layers, strong signals of hybridization are attributed to the complex Late Miocene/Early Pliocene palaeohistory of African rivers. Hybridization of multiple lineages across changing watersheds shaped each of the major haplochromine radiations in lakes Tanganyika, Victoria, Malawi and the Kalahari Palaeolakes, as well as a miniature species flock in the Congo basin (River Fwa). On the basis of our results, introgression occurred not only on a spatially restricted scale, but massively over almost the whole range of the haplochromine distribution. This provides an alternative view on the origin and exceptional high diversity of this enigmatic vertebrate group.
Tissue loss (white syndrome) in the coral
Montipora capitata
is a dynamic disease with multiple host responses and potential causes
Authors: Work Thierry M. , Russell Robin , Aeby Greta S.
Published: September 2012

Tissue loss diseases or white syndromes (WS) are some of the most important coral diseases because they result in significant colony mortality and morbidity, threatening dominant Acroporidae in the Caribbean and Pacific. The causes of WS remain elusive in part because few have examined affected corals at the cellular level. We studied the cellular changes associated with WS over time in a dominant Hawaiian coral,
Montipora capitata
, and showed that: (i) WS has rapidly progressing (acute) phases mainly associated with ciliates or slowly progressing (chronic) phases mainly associated with helminths or chimeric parasites; (ii) these phases interchanged and waxed and waned; (iii) WS could be a systemic disease associated with chimeric parasitism or a localized disease associated with helminths or ciliates; (iv) corals responded to ciliates mainly with necrosis and to helminths or chimeric parasites with wound repair; (v) mixed infections were uncommon; and (vi) other than cyanobacteria, prokaryotes associated with cell death were not seen. Recognizing potential agents associated with disease at the cellular level and the host response to those agents offers a logical deductive rationale to further explore the role of such agents in the pathogenesis of WS in
M. capitata
and helps explain manifestation of gross lesions. This approach has broad applicability to the study of the pathogenesis of coral diseases in the field and under experimental settings.
Sequence and chromatin determinants of cell-type–specific transcription factor binding
Authors: Arvey Aaron , Agius Phaedra , Noble William Stafford , Leslie Christina
Published: September 2012

Gene regulatory programs in distinct cell types are maintained in large part through the cell-type–specific binding of transcription factors (TFs). The determinants of TF binding include direct DNA sequence preferences, DNA sequence preferences of cofactors, and the local cell-dependent chromatin context. To explore the contribution of DNA sequence signal, histone modifications, and DNase accessibility to cell-type–specific binding, we analyzed 286 ChIP-seq experiments performed by the ENCODE Consortium. This analysis included experiments for 67 transcriptional regulators, 15 of which were profiled in both the GM12878 (lymphoblastoid) and K562 (erythroleukemic) human hematopoietic cell lines. To model TF-bound regions, we trained support vector machines (SVMs) that use flexible k-mer patterns to capture DNA sequence signals more accurately than traditional motif approaches. In addition, we trained SVM spatial chromatin signatures to model local histone modifications and DNase accessibility, obtaining significantly more accurate TF occupancy predictions than simpler approaches. Consistent with previous studies, we find that DNase accessibility can explain cell-line–specific binding for many factors. However, we also find that of the 10 factors with prominent cell-type–specific binding patterns, four display distinct cell-type–specific DNA sequence preferences according to our models. Moreover, for two factors we identify cell-specific binding sites that are accessible in both cell types but bound only in one. For these sites, cell-type–specific sequence models, rather than DNase accessibility, are better able to explain differential binding. Our results suggest that using a single motif for each TF and filtering for chromatin accessible loci is not always sufficient to accurately account for cell-type–specific binding profiles.
Spreading of X chromosome inactivation via a hierarchy of defined Polycomb stations
Authors: Pinter Stefan F. , Sadreyev Ruslan I. , Yildirim Eda , Jeon Yesu , Ohsumi Toshiro K. , Borowsky Mark , Lee Jeannie T.
Published: September 2012

X chromosome inactivation (XCI) achieves dosage balance in mammals by repressing one of two X chromosomes in females. During XCI, the long noncoding Xist RNA and Polycomb proteins spread along the inactive X (Xi) to initiate chromosome-wide silencing. Although inactivation is known to commence at the X-inactivation center (Xic), how it propagates remains unknown. Here, we examine allele-specific binding of Polycomb repressive complex 2 (PRC2) and chromatin composition during XCI and generate a chromosome-wide profile of Xi and Xa (active X) at nucleosome-resolution. Initially, Polycomb proteins are localized to ∼150 strong sites along the X and concentrated predominantly within bivalent domains coinciding with CpG islands (“canonical sites”). As XCI proceeds, ∼4000 noncanonical sites are recruited, most of which are intergenic, nonbivalent, and lack CpG islands. Polycomb sites are depleted of LINE repeats but enriched for SINEs and simple repeats. Noncanonical sites cluster around the ∼150 strong sites, and their H3K27me3 levels reflect a graded concentration originating from strong sites. This suggests that PRC2 and H3K27 methylation spread along a gradient unique to XCI. We propose that XCI is governed by a hierarchy of defined Polycomb stations that spread H3K27 methylation in cis.
Combining RT-PCR-seq and RNA-seq to catalog all genic elements encoded in the human genome
Authors: Howald Cédric , Tanzer Andrea , Chrast Jacqueline , Kokocinski Felix , Derrien Thomas , Walters Nathalie , Gonzalez Jose M. , Frankish Adam , Aken Bronwen L. , Hourlier Thibaut , Vogel Jan-Hinnerk , White Simon , Searle Stephen , Harrow Jennifer , Hubbard Tim J. , Guigó Roderic , Reymond Alexandre
Published: September 2012

Within the ENCODE Consortium, GENCODE aimed to accurately annotate all protein-coding genes, pseudogenes, and noncoding transcribed loci in the human genome through manual curation and computational methods. Annotated transcript structures were assessed, and less well-supported loci were systematically, experimentally validated. Predicted exon–exon junctions were evaluated by RT-PCR amplification followed by highly multiplexed sequencing readout, a method we called RT-PCR-seq. Seventy-nine percent of all assessed junctions are confirmed by this evaluation procedure, demonstrating the high quality of the GENCODE gene set. RT-PCR-seq was also efficient to screen gene models predicted using the Human Body Map (HBM) RNA-seq data. We validated 73% of these predictions, thus confirming 1168 novel genes, mostly noncoding, which will further complement the GENCODE annotation. Our novel experimental validation pipeline is extremely sensitive, far more than unbiased transcriptome profiling through RNA sequencing, which is becoming the norm. For example, exon–exon junctions unique to GENCODE annotated transcripts are five times more likely to be corroborated with our targeted approach than with extensive large human transcriptome profiling. Data sets such as the HBM and ENCODE RNA-seq data fail sampling of low-expressed transcripts. Our RT-PCR-seq targeted approach also has the advantage of identifying novel exons of known genes, as we discovered unannotated exons in ∼11% of assessed introns. We thus estimate that at least 18% of known loci have yet-unannotated exons. Our work demonstrates that the cataloging of all of the genic elements encoded in the human genome will necessitate a coordinated effort between unbiased and targeted approaches, like RNA-seq and RT-PCR-seq.
Linking disease associations with regulatory information in the human genome
Authors: Schaub Marc A. , Boyle Alan P. , Kundaje Anshul , Batzoglou Serafim , Snyder Michael
Published: September 2012

Genome-wide association studies have been successful in identifying single nucleotide polymorphisms (SNPs) associated with a large number of phenotypes. However, an associated SNP is likely part of a larger region of linkage disequilibrium. This makes it difficult to precisely identify the SNPs that have a biological link with the phenotype. We have systematically investigated the association of multiple types of ENCODE data with disease-associated SNPs and show that there is significant enrichment for functional SNPs among the currently identified associations. This enrichment is strongest when integrating multiple sources of functional information and when highest confidence disease-associated SNPs are used. We propose an approach that integrates multiple types of functional data generated by the ENCODE Consortium to help identify “functional SNPs” that may be associated with the disease phenotype. Our approach generates putative functional annotations for up to 80% of all previously reported associations. We show that for most associations, the functional SNP most strongly supported by experimental evidence is a SNP in linkage disequilibrium with the reported association rather than the reported SNP itself. Our results show that the experimental data sets generated by the ENCODE Consortium can be successfully used to suggest functional hypotheses for variants associated with diseases and other phenotypes.
Annotation of functional variation in personal genomes using RegulomeDB
Authors: Boyle Alan P. , Hong Eurie L. , Hariharan Manoj , Cheng Yong , Schaub Marc A. , Kasowski Maya , Karczewski Konrad J. , Park Julie , Hitz Benjamin C. , Weng Shuai , Cherry J. Michael , Snyder Michael
Published: September 2012

As the sequencing of healthy and disease genomes becomes more commonplace, detailed annotation provides interpretation for individual variation responsible for normal and disease phenotypes. Current approaches focus on direct changes in protein coding genes, particularly nonsynonymous mutations that directly affect the gene product. However, most individual variation occurs outside of genes and, indeed, most markers generated from genome-wide association studies (GWAS) identify variants outside of coding segments. Identification of potential regulatory changes that perturb these sites will lead to a better localization of truly functional variants and interpretation of their effects. We have developed a novel approach and database, RegulomeDB, which guides interpretation of regulatory variants in the human genome. RegulomeDB includes high-throughput, experimental data sets from ENCODE and other sources, as well as computational predictions and manual annotations to identify putative regulatory potential and identify functional variants. These data sources are combined into a powerful tool that scores variants to help separate functional variants from a large pool and provides a small set of putative sites with testable hypotheses as to their function. We demonstrate the applicability of this tool to the annotation of noncoding variants from 69 full sequenced genomes as well as that of a personal genome, where thousands of functionally associated variants were identified. Moreover, we demonstrate a GWAS where the database is able to quickly identify the known associated functional variant and provide a hypothesis as to its function. Overall, we expect this approach and resource to be valuable for the annotation of human genome sequences.
Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors
Authors: Wang Jie , Zhuang Jiali , Iyer Sowmya , Lin XinYing , Whitfield Troy W. , Greven Melissa C. , Pierce Brian G. , Dong Xianjun , Kundaje Anshul , Cheng Yong , Rando Oliver J. , Birney Ewan , Myers Richard M. , Noble William S. , Snyder Michael , Weng Zhiping
Published: September 2012

Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) has become the dominant technique for mapping transcription factor (TF) binding regions genome-wide. We performed an integrative analysis centered around 457 ChIP-seq data sets on 119 human TFs generated by the ENCODE Consortium. We identified highly enriched sequence motifs in most data sets, revealing new motifs and validating known ones. The motif sites (TF binding sites) are highly conserved evolutionarily and show distinct footprints upon DNase I digestion. We frequently detected secondary motifs in addition to the canonical motifs of the TFs, indicating tethered binding and cobinding between multiple TFs. We observed significant position and orientation preferences between many cobinding TFs. Genes specifically expressed in a cell line are often associated with a greater occurrence of nearby TF binding in that cell line. We observed cell-line–specific secondary motifs that mediate the binding of the histone deacetylase HDAC2 and the enhancer-binding protein EP300. TF binding sites are located in GC-rich, nucleosome-depleted, and DNase I sensitive regions, flanked by well-positioned nucleosomes, and many of these features show cell type specificity. The GC-richness may be beneficial for regulating TF binding because, when unoccupied by a TF, these regions are occupied by nucleosomes in vivo. We present the results of our analysis in a TF-centric web repository Factorbook (http://factorbook.org) and will continually update this repository as more ENCODE data are generated.
The Grapevine Expression Atlas Reveals a Deep Transcriptome Shift Driving the Entire Plant into a Maturation Program
Authors: Fasoli Marianna , Dal Santo Silvia , Zenoni Sara , Tornielli Giovanni Battista , Farina Lorenzo , Zamboni Anita , Porceddu Andrea , Venturini Luca , Bicego Manuele , Murino Vittorio , Ferrarini Alberto , Delledonne Massimo , Pezzotti Mario
Published: September 2012

We developed a genome-wide transcriptomic atlas of grapevine (Vitis vinifera) based on 54 samples representing green and woody tissues and organs at different developmental stages as well as specialized tissues such as pollen and senescent leaves. Together, these samples expressed ∼91% of the predicted grapevine genes. Pollen and senescent leaves had unique transcriptomes reflecting their specialized functions and physiological status. However, microarray and RNA-seq analysis grouped all the other samples into two major classes based on maturity rather than organ identity, namely, the vegetative/green and mature/woody categories. This division represents a fundamental transcriptomic reprogramming during the maturation process and was highlighted by three statistical approaches identifying the transcriptional relationships among samples (correlation analysis), putative biomarkers (O2PLS-DA approach), and sets of strongly and consistently expressed genes that define groups (topics) of similar samples (biclustering analysis). Gene coexpression analysis indicated that the mature/woody developmental program results from the reiterative coactivation of pathways that are largely inactive in vegetative/green tissues, often involving the coregulation of clusters of neighboring genes and global regulation based on codon preference. This global transcriptomic reprogramming during maturation has not been observed in herbaceous annual species and may be a defining characteristic of perennial woody plants.
Vascularisation of myringo‐/tympanoplastic grafts in active and inactive chronic mucosal otitis media: a prospective cohort study
Authors: Noh H. , Lee D.‐H.
Published: September 2012

Clin. Otolaryngol. 2012, 37, 355–361

Objectives:  To evaluate the vascularisation process of the grafted fascia or perichondrium in active and inactive chronic mucosal otitis media.

Design:  Prospective study.

Setting:  University‐based, secondary referral hospital.

Participants:  Two hundred thirty‐two patients who underwent type 1 tympanoplasty or myringoplasty by one experienced surgeon.

Main outcome measures:  After postoperative days 5–7, the graft was inspected using a binocular operating microscope at least twice weekly until vascularisation was confirmed to have commenced. This point was defined as the time of vascularisation. An intact graft at 3 months postoperatively was considered a closure success.

Results:  The mean time of vascularisation of 232 grafts was 14.2 ± 3.6 days (range 8–25). The vascularisation time differed according to the perforation size. The perforations involving 50% and less of the pars tensa were revascularised earlier than those involving 75% and more. There was no relationship between vascularisation time and closure success or failure. Age itself did not influence the vascularisation time or the risk of closure failure. Postoperative otorrhea was higher in patients with a preoperative wet middle ear mucosa than among those with a dry one.

Conclusion:  The vascularisation time was shorter in perforations of 50% and less than those of 75% and more but the rate of closure success was not different between two. The graft failure was not attributed to the failure of vascularisation. Age itself seemed not to be a contraindication for myringo‐/tympanoplasty in otherwise healthy elderly patients.
Proof of mechanism for the DGAT1 inhibitor AZD7687: results from a first‐time‐in‐human single‐dose study
Authors: Denison H. , Nilsson C. , Kujacic M. , Löfgren L. , Karlsson C. , Knutsson M. , Eriksson J. W.
Published: September 2012

Aims

Inhibition of diacylglycerol acyltransferase 1 (DGAT1), which catalyses the final step in triacylglycerol (TAG) assembly, is suggested as a treatment for type 2 diabetes and obesity based on animal data indicating insulin sensitization and weight reduction. This first‐time‐in‐human single ascending dose study explored the safety, tolerability, pharmacokinetics and pharmacodynamics of the selective DGAT1 inhibitor AZD7687.

Methods

Eighty healthy male subjects were enrolled. In each of 10 cohorts, six subjects received the same dose of AZD7687 orally (range across cohorts 1–60 mg) and two placebo. Plasma AZD7687 exposure was measured repeatedly. Postprandial serum TAG excursion was measured during 8 h after a standardized mixed meal with fat energy content of 60% (SMM 60%; five cohorts, 1–20 mg), before (baseline) and after dosing, to assess effects on gut DGAT1 activity.

Results

AZD7687 markedly reduced postprandial TAG excursion with a steep concentration–effect relationship. Incremental TAG AUC (area under the serum concentration vs. time curve) following SMM 60% was decreased >75% from baseline at doses ≥5 mg (p < 0.0001 vs. placebo). Serum levels of diacylglycerol, specifically measured with mass spectrometry, did not increase after AZD7687 administration. Nausea, vomiting and diarrhoea were reported with increasing doses and they limited dose escalation. Lowering of SMM fat content to 45 or 30% in five cohorts gradually reduced the frequency of gastrointestinal symptoms at a given dose of AZD7687.

Conclusions

The attenuating effect of AZD7687 on postprandial TAG excursion provides proof of mechanism with respect to gut DGAT1 inhibition. However, dose and diet‐related gastrointestinal side effects may impact further development of DGAT1 inhibitors.
Predicting skin penetration of actives from complex cosmetic formulations: an evaluation of inter formulation and inter active effects during formulation optimization for transdermal delivery
Authors: Wiechers J. W. , Watkinson A. C. , Cross S. E. , Roberts M. S.
Published: September 2012

Synopsis

Twenty products, containing a radiolabelled form of each active in typical cosmetic formulations, were made and applied to female human epidermal membranes mounted in Franz diffusion cells for 48 h under ‘in use’ conditions. The products consisted of combinations of five formulations (a hydro‐alcoholic gel, an oil in water emulsion, a water in oil emulsion, a microemulsion and an oil) with four model drug actives (testosterone, hydrocortisone, 5‐fluorouracil and ketoconazole). Steady‐state flux appeared to be reached by 8 h and maintained for all products, other than for the microemulsions, consistent with the actives being present in the residual formulation on the skin at saturation. The recovery for each active at the end of the 48‐h study (from a series of stratum corneum tape strips, the remaining skin, cumulative amount penetrating into the receptor solution, product washed from the skin and on the donor chamber cap) ranged from 86.5% to 100.6%. The rank order of the fluxes for the actives from the hydro‐alcoholic gel is consistent with the known active molecular size and polarity determinants for maximum epidermal flux. Actives with similar steady‐state (maximum) fluxes from a range of formulations had retention in the stratum corneum and similar transport rate constants through the stratum corneum. The microemulsion formulation significantly enhanced both the stratum corneum steady‐state flux and transport rate constant for 5‐fluorouracil, hydrocortisone and testosterone. The penetration flux of each active could be related to its size and polarity and appeared maximal when the actives in the different cosmetic formulations applied to the skin under ‘in use’ conditions were likely to remain in the residual product on the skin as a saturated solution after solvent evaporation. Enhanced penetration fluxes can be achieved by formulation selection and an appropriate choice/mix of emollients/adjuvants. The principles described here provide a framework for understanding the delivery of cosmetic ingredients from various formulations.
Effects of temperature and food supply on the growth of whitefish Coregonus lavaretus larvae in an oligotrophic peri‐alpine lake
Authors: Perrier C. , Molinero J. C. , Gerdeaux D. , Anneville O.
Published: September 2012

The relative roles of temperature and food availability on the seasonal and daily growth of whitefish Coregonus lavaretus larvae were investigated in the oligotrophic peri‐alpine Lake Annecy, France. During the spring from 2004 to 2007, surface water temperature and density of potential zooplankton prey were monitored, and 2688 larvae were caught and measured. In addition, the daily growth of 130 larvae was estimated retrospectively by investigating the microstructure of their otoliths. Temperature played the predominant role in controlling both seasonal and daily growth of early larvae. In contrast, the abundance of Mesocyclops leuckarti and larval density was only slightly correlated to larval growth, suggesting no food limitation nor strong interindividual competition over the study period. Overall, these findings run counter to concerns about potential food limitation, but sound a warning about the potential impact of climate change on fish ecology and fisheries management.
Priming of the Arabidopsis pattern‐triggered immunity response upon infection by necrotrophic Pectobacterium carotovorum bacteria
Authors: Po‐Wen Chen , Singh Prashant , Zimmerli Laurent
Published: September 2012

Boosted responsiveness of plant cells to stress at the onset of pathogen‐ or chemically induced resistance is called priming. The chemical β‐aminobutyric acid (BABA) enhances Arabidopsis thaliana resistance to hemibiotrophic bacteria through the priming of the salicylic acid (SA) defence response. Whether BABA increases Arabidopsis resistance to the necrotrophic bacterium Pectobacterium carotovorum ssp. carotovorum (Pcc) is not clear. In this work, we show that treatment with BABA protects Arabidopsis against the soft‐rot pathogen Pcc. BABA did not prime the expression of the jasmonate/ethylene‐responsive gene PLANT DEFENSIN 1.2 (PDF1.2), the up‐regulation of which is usually associated with resistance to necrotrophic pathogens. Expression of the SA marker gene PATHOGENESIS RELATED 1 (PR1) on Pcc infection was primed by BABA treatment, but SA‐defective mutants demonstrated a wild‐type level of BABA‐induced resistance against Pcc. BABA primed the expression of the pattern‐triggered immunity (PTI)‐responsive genes FLG22‐INDUCED RECEPTOR‐LIKE KINASE 1 (FRK1), ARABIDOPSIS NON‐RACE SPECIFIC DISEASE RESISTANCE GENE (NDR1)/HAIRPIN‐INDUCED GENE (HIN1)‐LIKE 10 (NHL10) and CYTOCHROME P450, FAMILY 81 (CYP81F2) after inoculation with Pcc or after treatment with purified bacterial microbe‐associated molecular patterns, such as flg22 or elf26. PTI‐mediated callose deposition was also potentiated in BABA‐treated Arabidopsis, and BABA boosted Arabidopsis stomatal immunity to Pcc. BABA treatment primed the PTI response in the SA‐defective mutants SA induction deficient 2‐1 (sid2‐1) and phytoalexin deficient 4‐1 (pad4‐1). In addition, BABA priming was associated with open chromatin configurations in the promoter region of PTI marker genes. Our data indicate that BABA primes the PTI response upon necrotrophic bacterial infection and suggest a role for the PTI response in BABA‐induced resistance.
The impact on cardiac diagnosis and mortality of focused transthoracic echocardiography in hip fracture surgery patients with increased risk of cardiac disease: a retrospective cohort study
Authors: Canty D. J. , Royse C. F. , Kilpatrick D. , Bowyer A. , Royse A. G.
Published: September 2012

Hip fracture surgery is associated with a high rate of mortality and morbidity; heart disease is the leading cause and is often unrecognised and inadequately treated. Pre‐operative focused transthoracic echocardiography by anaesthetists frequently influences management, but mortality outcome studies have not been performed to date. Mortality over the 12 months after hip fracture surgery, in 64 patients at risk of cardiac disease who received pre‐operative echocardiography, was compared with 66 randomised historical controls who did not receive echocardiography. Mortality was lower in the group that received echocardiography over the 30 days (4.7% vs 15.2%, log rank p = 0.047) and 12 months after surgery (17.1% vs 33.3%, log rank p = 0.031). Hazard of death was also reduced with pre‐operative echocardiography over 12 months after adjustment for known risk factors (hazard ratio 0.41, 95% CI 0.2–0.85, p = 0.016). Pre‐operative echocardiography was not associated with a delay in surgery. These data support a randomised controlled trial to confirm these findings.
Molecular cloning and characterization of peroxiredoxin 4 involved in protection against oxidative stress in the silkworm Bombyx mori
Authors: Shi G‐Q. , Yu Q‐Y. , Shi L. , Zhang Z.
Published: September 2012

Peroxiredoxins (Prxs) are a ubiquitous family of proteins that play important roles in insects in protection against oxidative stress through the detoxification of cellular peroxides. Here, we describe the cloning and characterization of a Prx4 cDNA of the silkworm Bombyx mori (BmPrx4). The BmPrx4 gene has an open reading frame of 744 bp encoding 248 amino acids and a conserved motif, VCP, involved in its presumed redox functions. The heterologously expressed proteins of the gene in Escherichia coli showed antioxidant activity, removed hydrogen peroxide and protected DnA. Western blotting analysis showed the presence of BmPrx4 in the haemolymph, suggesting that the protein is secretable. Moreover, BmPrx4 was expressed at all developmental stages. The expression level of BmPrx4 was relatively low during the feeding stage but high at the wandering stage. BmPrx4 was induced by quercetin or temperature stress. Immunohistochemical analysis revealed that BmPrx4 is present in the brain, neurones and olfactory organ of the head in silkworms. Overall, our results indicate that the expression profile of BmPrx4 correlates well with protection from oxidative damage. Our data provide clues for the development of control technology for agricultural and forestry pests as the silkworm is a representative of lepidopteran pests.
The Responses of Multiple Cytokines Following Incubation of Whole Blood from TB Patients, Latently Infected Individuals and Controls with the TB Antigens ESAT‐6, CFP‐10 and TB7.7
Authors: Kim S. Y. , Park M. S. , Kim Y. S. , Kim S. K. , Chang J. , Lee H. J. , Cho S.‐N. , Kang Y. A.
Published: September 2012

The development of clinically relevant biomarkers is important for diagnosing latent tuberculosis infection (LTBI) and active tuberculosis (TB) and predicting their prognoses. This study examined whether the responses of multiple cytokines can be used as a biomarker to distinguish the TB infection status and mycobacterial load. We analysed the responses of multiple cytokines (IFN‐γ, IL‐2, IL‐10, IL‐13, IL‐17 and TNF‐α) in the supernatant from the QuantiFERON‐TB Gold In‐Tube assay following stimulation of whole blood from the TB group (n = 32), LTBI group (n = 19) and healthy controls (n = 30) with TB antigens (ESAT‐6, CFP‐10 and TB7.7). The median responses of IFN‐γ, IL‐2, IL‐10 and IL‐13 were higher in the LTBI and active TB groups than in the non‐TB control group (IFN‐γ, P < 0.001; IL‐2, P < 0.001; IL‐10, P = 0.012; IL‐13, P < 0.001). The median IL‐2/IFN‐γ ratio of the LTBI group was higher than that of the active TB group (P = 0.014) and differed significantly between patients with LTBI, patients with smear‐negative TB and patients with smear‐positive TB (P = 0.027). This difference was especially evident between the patients with LTBI and patients with smear‐positive TB (P = 0.047). In conclusion, IFN‐γ, IL‐2, IL‐10 and IL‐13 can serve as biomarkers for distinguishing TB infection. In addition, the IL‐2/IFN‐γ ratio appears to be a biomarker for diagnosing LTBI and may be useful as a prognostic factor and for evaluating treatment responses.
Can the rural poor in India afford to treat non‐communicable diseases
Authors: Binnendijk Erika , Koren Ruth , Dror David M.
Published: September 2012

Objective  Non‐communicable diseases (NCD) are on the increase in low‐income countries, where healthcare costs are paid mostly out‐of‐pocket. We investigate the financial burden of NCD vs. communicable diseases (CD) among rural poor in India and assess whether they can afford to treat NCD.

Methods  We used data from two household surveys undertaken in 2009–2010 among 7389 rural poor households (39 205 individuals) in Odisha and Bihar. All persons from the sampled households, irrespective of age and gender, were included in the analysis. We classify self‐reported illnesses as NCD, CD or ‘other morbidities’ following the WHO classification.

Results  Non‐communicable diseases accounted for around 20% of the diseases in the month preceding the survey in Odisha and 30% in Bihar. The most prevalent NCD, representing the highest share in outpatient costs, were musculoskeletal, digestive and cardiovascular diseases. Cardiovascular and digestive problems also generated the highest inpatient costs. Women, older persons and less‐poor households reported higher prevalence of NCD. Outpatient costs (consultations, medicines, laboratory tests and imaging) represented a bigger share of income for NCD than for CD. Patients with NCD were more likely to report a hospitalisation.

Conclusion  Patients with NCD in rural poor settings in India pay considerably more than patients with CD. For NCD cases that are chronic, with recurring costs, this would be aggravated. The cost of NCD care consumes a big part of the per person share of household income, obliging patients with NCD to rely on informal intra‐family cross‐subsidisation. An alternative solution to finance NCD care for rural poor patients is needed.
Thermoregulation in moulting and feeding Danaus plexippus L. (Lepidoptera: Nymphalidae) caterpillars
Authors: Serratore Vanessa R , Zalucki Myron P , Carter Patrick A
Published: September 2012

Body temperature in insects is affected by interactions between environmental variables, behavioural choices and the physiological state of the animal. Insect larvae display a number of tactics for thermoregulation which allow their body temperatures to deviate several degrees from ambient. Thermoregulatory adaptations can reduce generation time and allow higher population growth rates. However, few investigations have examined thermoregulation of moulting larvae. This study measured whether moulting Monarch butterfly (Danaus plexippus) larvae thermoregulate, and, if so, whether they thermoregulate similarly to feeding larvae. Body temperatures of moulting and feeding larvae were compared to their microhabitat temperatures. In three of four environments, feeding larvae were able to thermoregulate in such a way that their body temperature was higher than ambient at low ambient temperature, and lower than ambient at higher ambient temperature. However, moulting larvae appear not to thermoregulate because their body temperature did not differ from ambient in three of four environments. These results pose the question of whether larvae are behaviourally and/or physiologically constrained from thermoregulating during the moulting process. Additional studies are needed to address such questions and would help to elucidate the impact of thermoregulation of moulting larvae on the ecology and evolution of insects.
Honeydew as a source of nutrition for Lysiphlebus testaceipes (Cresson) (Hymenoptera: Braconidae): effect of adult diet on lifespan and egg load
Authors: Hopkinson Jamie E , Zalucki Myron P , Murray David A H
Published: September 2012

Parasitoid survival and fecundity is generally enhanced with access to carbohydrate food sources. In many agricultural ecosystems, there is often a scarcity of suitable carbohydrates for parasitoids. This study compared the suitability of aphid honeydew and buckwheat nectar as diet for the aphid parasitoid Lysiphlebus testaceipes. Wasp lifespan and egg load were both increased with access to carbohydrates, but no differences were detected between the various carbohydrates diets tested. As aphid honeydew is a sufficient source of nutrition and L. testaceipes is a short‐lived species, adding additional sources of carbohydrates like floral nectar strips to the agricultural landscape is unlikely to significantly increase the biological control exerted by L. testaceipes.
Mobilities and Knowledge Transfer: Understanding the Contribution of Volunteer Stays to North–South Healthcare Partnerships
Authors: Ackers Helen Louise
Published: September 2012

In this paper, I review recent literature on the relationship between human mobility and knowledge transfer processes, and apply some of the more theoretical ideas to an evaluation of the kinds of mobility in whichUKparticipants engage in the context of North–South healthcare partnerships (HCPs). Much of the contemporary research on highly skilled mobility highlights the role that short stays and circular mobility play in knowledge transfer processes. I consider the value of short stays in the travel–mobility–migration continuum and the contribution they make to the transfer, translation and effectiveness of knowledge. Healthcare partnerships are best conceptualized as knowledge networks, with various forms of mobility (both physical and virtual) playing a critical role in network‐generation, evolution and impact. I outline the findings of two studies. The first is an evaluation ofHCPs (Ackers and Porter, 2011) and the second an in‐depth ongoing evaluation of oneHCPknown as the Liverpool–Mulago Partnership orLMP1(Porter et al., 2011). The results raise questions about the relationship between the different types of mobility that participants inHCPs (predominantly professional volunteers) engage in, particularly the duration and repeated quality of stays, and knowledge transfer processes. Williams argues that “there are still major gaps in our understanding of the specific contribution of international migration to knowledge transfer, of the processes involved, and of the conditions that facilitate this” (2006 588). In this paper, I begin to close some of these gaps and advance our understanding of the relationship between different forms of mobility and knowledge transfer processes, in the hopes that this will build the evidence base supporting the contribution of North–SouthHCPs to the achievement of the Millennium Development Goals2.
Decreasing the Recent Immigrant Earnings Gap: The Impact of Canadian Credential Attainment
Authors: Banerjee Rupa , Lee Byron Y.
Published: September 2012

It is well documented that newly arrived immigrants face a significant earnings gap relative to native‐born workers. One way for new immigrants to improve their relative labour market position upon arrival in a host country is to improve their educational credentials. According to signalling theory, a host‐country credential should provide employers with a proxy for true productivity on the job, leading to higher earnings. Using data from a Canadian longitudinal survey, we employ longitudinal growth‐curve techniques to estimate the effect of receiving a Canadian educational credential on the income growth of racial‐minority recent immigrants compared to native‐born Canadians. The results indicate that the earnings gap between recent immigrants and native‐born Canadians is significantly reduced with the attainment of a Canadian educational credential.
Bangladeshi Migrant Workers in Hong Kong: Adaptation Strategies in an Ethnically Distant Destination
Authors: Ahsan Ullah A.K.M.
Published: September 2012

The paper attempts to explore the adaptation‐related challenges that Bangladeshi migrant workers in Hong Kong face and the strategies they adopt to triumph over them. Data were collected through administering both closed and open‐ended questionnaires to 56 migrant workers in Hong Kong during 2005–2006. The study revealed that most of the respondents stayed in Hong Kong legally but worked illegally because of the fact that although they could extend their stay permits, they were not grated work permits. This exclusive circumstance places them in a number of difficult situations. In attempting to adapt to Hong Kong society, they embrace a number of interesting and unique strategies to surmount challenges.
Class, gender and time poverty: a time‐use analysis of British workers’ free time resources
Authors: Chatzitheochari Stella , Arber Sara
Published: September 2012

Free time, that is, the time that remains at one's own discretion after conducting daily work and personal care activities, has been previously recognized as a ‘primary good’ and an important welfare resource that provides opportunities for participation in social life and leisure. However, recent years have witnessed an increasing preoccupation with the phenomenon of time poverty, drawing attention to the distribution of free time and its relationship to structural and family circumstances. In this article we propose a novel approach to the measurement of time poverty and document its occurrence amongst British workers. In line with previous literature, a conceptualization of time poverty as a relative lack of free time resources vis‐à‐vis other members of the community is adopted. However, unlike previous empirical studies, we investigate the differential configuration of time poverty on weekdays and weekend days, alongside indicators of the quality of free time, taking into account insights from theoretical and empirical work within the field of the sociology of time. Our analysis of the 2000 UK Time Use Survey highlights class and gender inequalities that have been missed by previous measurement approaches and demonstrates that, overall, working women experience multiple and more severe free time constraints, which may constitute an additional barrier for their leisure and social participation.
Correlation between posterior offset of femoral condyles and sagittal slope of the tibial plateau
Authors: Cinotti G. , Sessa P. , Ripani F. R. , Postacchini R. , Masciangelo R. , Giannicola G.
Published: September 2012

The aim of this study was to address, in normal knees, the variability of posterior offset of femoral condyles and tibial slope, and the presence of any correlation between the two that might be needed to achieve an adequate joint motion in flexion. Magnetic resonance images of normal knees of 80 subjects, 45 males and 35 females, with a mean age of 38.9 years, were analysed. Measurements were performed by two independent observers using an imaging visualization software. The tibial slope averaged 8 and 7.7 °, on the medial and lateral sides, respectively (P = 0.2); the mean posterior offset of femoral condyles was 27.4 and 25.2 mm on the two sides, respectively (P = 0.0001). The variation coefficient of the condylar offset and tibial slope was 11.5 and 38%, respectively. In the medial compartment, a significant correlation was found between the femoral condylar offset and the tibial slope, while the same was not observed in the lateral compartment of the knee. Magnetic resonance imaging allows the assessment of tibial slope and femoral condylar offset in the medial and lateral side separately, taking into account any difference between the two compartments. The sagittal tibial slope exhibits a greater variability compared with the posterior offset of femoral condyles. The correlation found, in the medial compartment, between the tibial slope and femoral condylar offset suggests that the reconstitution of the proper morphology of the posterior part of the knee joint may be necessary to obtain a full range of motion in flexion after total knee replacement.
Trainee teachers with dyslexia: personal narratives of resilience
Authors: Glazzard Jonathan , Dale Kirsty
Published: September 2012

This paper tells the stories of two trainee teachers and their personal experiences of dyslexia. Both informants were English and training to be primary school teachers in England. Through drawing on their own experiences of education, the stories illustrate how dyslexia has shaped the self‐concept, self‐esteem and resilience of each informant. The narratives presented in this paper illustrate powerfully the ways in which teachers can have a positive or negative impact on the self‐concepts of students with dyslexia. Both had been inspired by teachers they had met, and these positive role models had given them the confidence to pursue their own ambitions. However, both had encountered teachers who lacked empathy and patience, and these teachers had a detrimental impact on their self‐concepts. For both of these trainee teachers, personal experiences of dyslexia also shaped their professional identities as teachers. Both trainees described themselves as caring and empathic teachers, suggesting that personal experiences of dyslexia had a positive impact on teacher professional identity.