bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and genotype distribution of cervical human papillomavirus infection among female sex workers in Asia: a systematic literature review and meta-analysis
Authors: Peng Rui-Rui , Li Hong-Min , Chang Helena , Li Jian-Hong , Wang Alberta L. , Chen Xiang-Sheng
Published: November 2011

Cervical human papillomavirus (HPV) infection is highly transmissible. Although there are many studies on HPV infection in general population of women globally, little attention has been paid to female sex workers (FSWs) in Asia. In this study, we used a meta-analytic approach to systematically analyse the literature to elucidate the prevalence and genotype distribution of cervical HPV infection among FSWs in Asia. Fourteen eligible studies were identified in five databases, and data including 4198 FSWs from nine Asian countries were aggregated. Crude estimates of cervical HPV prevalence among FSWs in this region ranged from 12.8% to 84.8%. FSWs had a nearly 10-fold risk of HPV infection than the general population of women. Stratified analysis showed that HPV prevalence was higher in East Asia than other subregions and in younger FSWs than older FSWs. HPV genotype distribution was statistically different between East Asia and South-east Asia. In East Asia, the most prevalent genotypes were HPV 16 (23.9%), 18 (11.0%), 58 (9.4%), 56 (6.3%) and 52 (5.3%), while they were HPV 52 (12.9%), 16 (8.5%), 58 (5.2%), 18 (5.0%) and 66 (4.9%) in South-east Asia. HPV 31, 33 and 35 were less frequently found in both subregions. HPV infection was substantial among FSWs in some Asian countries. More studies are necessary to illustrate the overall picture of HPV infection in this region.
Unexpected role of anticoagulant protein C in controlling epithelial barrier integrity and intestinal inflammation
Authors: Vetrano Stefania , Ploplis Victoria A. , Sala Emanuela , Sandoval-Cooper Mayra , Donahue Deborah L. , Correale Carmen , Arena Vincenzo , Spinelli Antonino , Repici Alessandro , Malesci Alberto , Castellino Francis J. , Danese Silvio
Published: November 2011

The protein C (PC) pathway is a well-characterized coagulation system. Endothelial PC receptors and thrombomodulin mediate the conversion of PC to its activated form, a potent anticoagulant and anti-inflammatory molecule. Here we show that the PC pathway is expressed on intestinal epithelial cells. The epithelial expression of PC and endothelial PC receptor is down-regulated In patients with inflammatory bowel disease. PC
−/−
/PC(Tg) mice, expressing only 3% of WT PC, developed spontaneous intestinal inflammation and were prone to severe experimental colitis. These mice also demonstrated spontaneous elevated production of inflammatory cytokines and increased intestinal permeability. Structural analysis of epithelial tight junction molecules revealed that lack of PC leads to decreased JAM-A and claudin-3 expression and an altered pattern of ZO-1 expression. In vitro, treatment of epithelial cells with activated PC led to protection of tight junction disruption induced by TNF-α, and in vivo, topical treatment with activated PC led to mucosal healing and amelioration of colitis. Taken together, these findings demonstrate that the PC pathway is a unique system involved in controlling intestinal homeostasis and inflammation by regulating epithelial barrier function.
T-cell factor 1 is a gatekeeper for T-cell specification in response to Notch signaling
Authors: Germar Kristine , Dose Marei , Konstantinou Tassos , Zhang Jiangwen , Wang Hongfang , Lobry Camille , Arnett Kelly L. , Blacklow Stephen C. , Aifantis Iannis , Aster Jon C. , Gounari Fotini
Published: November 2011

Although transcriptional programs associated with T-cell specification and commitment have been described, the functional hierarchy and the roles of key regulators in structuring/orchestrating these programs remain unclear. Activation of Notch signaling in uncommitted precursors by the thymic stroma initiates the T-cell differentiation program. One regulator first induced in these precursors is the DNA-binding protein T-cell factor 1 (Tcf-1), a T-cell–specific mediator of Wnt signaling. However, the specific contribution of Tcf-1 to early T-cell development and the signals inducing it in these cells remain unclear. Here we assign functional significance to Tcf-1 as a gatekeeper of T-cell fate and show that Tcf-1 is directly activated by Notch signals. Tcf-1 is required at the earliest phase of T-cell determination for progression beyond the early thymic progenitor stage. The global expression profile of Tcf-1–deficient progenitors indicates that basic processes of DNA metabolism are down-regulated in its absence, and the blocked T-cell progenitors become abortive and die by apoptosis. Our data thus add an important functional relationship to the roadmap of T-cell development.
FERM-dependent E3 ligase recognition is a conserved mechanism for targeted degradation of lipoprotein receptors
Authors: Calkin Anna C. , Goult Benjamin T. , Zhang Li , Fairall Louise , Hong Cynthia , Schwabe John W. R. , Tontonoz Peter
Published: November 2011

The E3 ubiquitin ligase IDOL (inducible degrader of the LDL receptor) regulates LDL receptor (LDLR)-dependent cholesterol uptake, but its mechanism of action, including the molecular basis for its stringent specificity, is poorly understood. Here we show that IDOL uses a singular strategy among E3 ligases for target recognition. The IDOL FERM domain binds directly to a recognition sequence in the cytoplasmic tails of lipoprotein receptors. This physical interaction is independent of IDOL's really interesting new gene (RING) domain E3 ligase activity and its capacity for autoubiquitination. Furthermore, IDOL controls its own stability through autoubiquitination of a unique FERM subdomain fold not present in other FERM proteins. Key residues defining the IDOL–LDLR interaction and IDOL autoubiquitination are functionally conserved in their insect homologs. Finally, we demonstrate that target recognition by IDOL involves a tripartite interaction between the FERM domain, membrane phospholipids, and the lipoprotein receptor tail. Our data identify the IDOL–LDLR interaction as an evolutionarily conserved mechanism for the regulation of lipid uptake and suggest that this interaction could potentially be exploited for the pharmacologic modulation of lipid metabolism.
The electrochemistry of quinizarin revealed through its mediated reduction of oxygen
Authors: Batchelor-McAuley Christopher , Dimov Ivan B. , Aldous Leigh , Compton Richard G.
Published: November 2011

After 35 years the hunt for improved anthracycline antibiotics is unabated but has yet to achieve the levels of clinical success desired. Electrochemical techniques provide a large amount of kinetic and thermodynamic information, but the use of such procedures is hindered by issues of sensitivity and selectivity. This work demonstrates how by harnessing the mechanism of catalytic reduction of oxygen by the quinone functionality present within the anthracycline structure it is possible to study the reactive moiety in nanomolar concentration. This methodology allows electrochemical investigation of the intercalation of quinizarin into DNA and, in particular, the quinone oxidation and degradation mechanism. The reversible reduction of the quinizarin, which in the presence of oxygen leads to the formation of reactive oxygen species, is found to occur at -0.535 V (vs. SCE) pH 6.84 and the irreversible oxidation leading to the molecules degradation occurs at +0.386 V (vs. SCE) pH 6.84.
Analysis of symmetry breaking mechanisms and the role of turbulence self-regulation in intrinsic rotation
Authors: Kwon J.M. , Yi S. , Rhee T. , Diamond P.H. , Miki K. , Hahm T.S. , Kim J.Y. , Gürcan Ö.D. , McDevitt C.
Published: November 2011

We present analyses of mechanisms which convert radial inhomogeneity to broken k
||-symmetry and thus produce turbulence driven intrinsic rotation in tokamak plasmas. By performing gyrokinetic simulations of ITG turbulence, we explore the many origins of broken k
||-symmetry in the fluctuation spectrum and identify both E × B shear and the radial gradient of turbulence intensity—a ubiquitous radial inhomogeneity in tokamak plasmas—as important k
||-symmetry breaking mechanisms. By studying and comparing the correlations between residual stress, E × B shearing, fluctuation intensity and its radial gradient, we investigate the dynamics of residual stress generation by various symmetry breaking mechanisms and explore the implication of the self-regulating dynamics of fluctuation intensity and E × B shearing for intrinsic rotation generation. Several scalings for intrinsic rotation are reported and are linked to investigations of underlying local dynamics. It is found that stronger intrinsic rotation is generated for higher values of ion temperature gradient, safety factor and weaker magnetic shear. These trends are broadly consistent with the intrinsic rotation scaling found from experiment—the so-called Rice scaling.
PGDSpider: an automated data conversion tool for connecting population genetics and genomics programs
Authors: Lischer H. E. L. , Excoffier L.
Published: November 2011

Summary: The analysis of genetic data often requires a combination of several approaches using different and sometimes incompatible programs. In order to facilitate data exchange and file conversions between population genetics programs, we introduce PGDSpider, a Java program that can read 27 different file formats and export data into 29, partially overlapping, other file formats. The PGDSpider package includes both an intuitive graphical user interface and a command-line version allowing its integration in complex data analysis pipelines.

Availability: PGDSpider is freely available under the BSD 3-Clause license on http://cmpg.unibe.ch/software/PGDSpider/

Contact:  heidi.lischer@iee.unibe.ch

Supplementary information:  Supplementary data are available at Bioinformatics online.
NTRC and Chloroplast-Generated Reactive Oxygen Species Regulate Pseudomonas syringae pv. tomato Disease Development in Tomato and Arabidopsis
Authors: Ishiga Yasuhiro , Ishiga Takako , Wangdi Tamding , Mysore Kirankumar S. , Uppalapati Srinivasa Rao
Published: November 2011

Coronatine (COR)-producing pathovars of Pseudomonas syringae, including pvs. tomato, maculicola, and glycinea, cause important diseases on tomato, crucifers, and soybean, respectively, and produce symptoms with necrotic lesions surrounded by chlorosis. The chlorosis is mainly attributed to COR. However, the significance of COR-induced chlorosis in localized lesion development and the molecular basis of disease-associated cell death is largely unknown. To identify host (chloroplast) genes that play a role in COR-mediated chlorosis, we used a forward genetics approach using Nicotiana benthamiana and virus-induced gene silencing and identified a gene which encodes 2-Cys peroxiredoxin (Prxs) that, when silenced, produced a spreading hypersensitive or necrosis-like phenotype instead of chlorosis after COR application in a COI1-dependent manner. Loss-of-function analysis of Prx and NADPH-dependent thioredoxin reductase C (NTRC), the central players of a chloroplast redox detoxification system, resulted in spreading accelerated P. syringae pv. tomato DC3000 disease-associated cell death with enhanced reactive oxygen species (ROS) accumulation in a COR-dependent manner in tomato and Arabidopsis. Consistent with these results, virulent strain DC3000 suppressed the expression of Prx and NTRC in Arabidopsis and tomato during pathogenesis. However, interestingly, authentic COR suppressed the expression of Prx and NTRC in tomato but not in Arabidopsis, suggesting that COR in conjunction with other effectors may modulate ROS and cell death in different host species. Taken together, these results indicated that NTRC or Prx function as a negative regulator of pathogen-induced cell death in the healthy tissues that surround the lesions, and COR-induced chloroplast-localized ROS play a role in enhancing the disease-associated cell death.
Identification of Pathogenesis-Associated Genes by T-DNA–Mediated Insertional Mutagenesis in Botrytis cinerea: A Type 2A Phosphoprotein Phosphatase and an SPT3 Transcription Factor Have Significant Impact on Virulence
Authors: Giesbert S. , Schumacher J. , Kupas V. , Espino J. , Segmüller N. , Haeuser-Hahn I. , Schreier P. H. , Tudzynski P.
Published: November 2011

Agrobacterium tumefaciens–mediated transformation (ATMT) was used to generate an insertional mutant library of the gray mold fungus Botrytis cinerea. From a total of 2,367 transformants, 68 mutants showing significant reduction in virulence on tomato and bean plants were analyzed in detail. As reported for other fungal ATMT libraries, integrations were mostly single copy, occurred preferentially in noncoding (regulatory) regions, and were frequently accompanied by small deletions of the target sequences and loss of parts of the border sequence. Two T-DNA integration events that were found to be linked to virulence were characterized in more detail: a catalytic subunit of a PP2A serine/threonine protein phosphatase (BcPP2Ac) and the SPT3 subunit of a Spt-Ada-Gcn5-acetyltransferase (SAGA-like) transcriptional regulator complex. Gene replacement and silencing approaches revealed that both Bcpp2Ac and SPT3 are crucial for virulence, growth, and differentiation as well as for resistance to H2O2 in B. cinerea.
The Plant Host Brassica napus Induces in the Pathogen Verticillium longisporum the Expression of Functional Catalase Peroxidase Which Is Required for the Late Phase of Disease
Authors: Singh Seema , Braus-Stromeyer Susanna A. , Timpner Christian , Valerius Oliver , von Tiedemann Andreas , Karlovsky Petr , Druebert Christine , Polle Andrea , Braus Gerhard H.
Published: November 2011

The devastating soilborne fungal pathogen Verticillium longisporum is host specific to members of the family Brassicaceae, including oilseed rape (Brassica napus) as the economically most important crop. The fungus infects through the roots and causes stunting and early senescence of susceptible host plants and a marked decrease in crop yield. We show here that V. longisporum reacts to the presence of B. napus xylem sap with the production of six distinct upregulated and eight downregulated proteins visualized by two-dimensional gel electrophoresis. Identification of 10 proteins by mass spectrometry revealed that all upregulated proteins are involved in oxidative stress response. The V. longisporum catalase peroxidase (VlCPEA) was the most upregulated protein and is encoded by two isogenes, VlcpeA-1 and VlcpeA-2. Both genes are 98% identical, corroborating the diploid or “amphihaploid” status of the fungus. Knock downs of both VlcpeA genes reduced protein expression by 80% and resulted in sensitivity against reactive oxygen species. Whereas saprophytic growth and the initial phase of the plant infection were phenotypically unaffected, the mutants were not able to perform the late phases of disease. We propose that the catalase peroxidase plays a role in protecting the fungus from the oxidative stress generated by the host plant at an advanced phase of the disease.
Salicylic Acid Regulates Basal Resistance to Fusarium Head Blight in Wheat
Authors: Makandar Ragiba , Nalam Vamsi J. , Lee Hyeonju , Trick Harold N. , Dong Yanhong , Shah Jyoti
Published: November 2011

Fusarium head blight (FHB) is a destructive disease of cereal crops such as wheat and barley. Previously, expression in wheat of the Arabidopsis NPR1 gene (AtNPR1), which encodes a key regulator of salicylic acid (SA) signaling, was shown to reduce severity of FHB caused by Fusarium graminearum. It was hypothesized that SA signaling contributes to wheat defense against F. graminearum. Here, we show that increased accumulation of SA in fungus-infected spikes correlated with elevated expression of the SA-inducible pathogenesis-related 1 (PR1) gene and FHB resistance. In addition, FHB severity and mycotoxin accumulation were curtailed in wheat plants treated with SA and in AtNPR1 wheat, which is hyper-responsive to SA. In support of a critical role for SA in basal resistance to FHB, disease severity was higher in wheat expressing the NahG-encoded salicylate hydroxylase, which metabolizes SA. The FHB-promoting effect of NahG was overcome by application of benzo (1,2,3), thiadiazole-7 carbothioic acid S-methyl ester, a synthetic functional analog of SA, thus confirming an important role for SA signaling in basal resistance to FHB. We further demonstrate that jasmonate signaling has a dichotomous role in wheat interaction with F. graminearum, constraining activation of SA signaling during early stages of infection and promoting resistance during the later stages of infection.
Involvement of a Class III Peroxidase and the Mitochondrial Protein TSPO in Oxidative Burst Upon Treatment of Moss Plants with a Fungal Elicitor
Authors: Lehtonen Mikko T. , Akita Motomu , Frank Wolfgang , Reski Ralf , Valkonen Jari P. T.
Published: November 2011

Production of apoplastic reactive oxygen species (ROS), or oxidative burst, is among the first responses of plants upon recognition of microorganisms. It requires peroxidase or NADPH oxidase (NOX) activity and factors maintaining cellular redox homeostasis. Here, PpTSPO1 involved in mitochondrial tetrapyrrole transport and abiotic (salt) stress tolerance was tested for its role in biotic stress in Physcomitrella patens, a nonvascular plant (moss). The fungal elicitor chitin caused an immediate oxidative burst in wild-type P. patens but not in the previously described ΔPrx34 mutants lacking the chitin-responsive secreted class III peroxidase (Prx34). Oxidative burst in P. patens was associated with induction of the oxidative stress-related genes AOX, LOX7, and NOX, and also PpTSPO1. The available ΔPpTSPO1 knockout mutants overexpressed AOX and LOX7 constitutively, produced 2.6-fold more ROS than wild-type P. patens, and exhibited increased sensitivity to a fungal necrotrophic pathogen and a saprophyte. These results indicate that Prx34, which is pivotal for antifungal resistance, catalyzes ROS production in P. patens, while PpTSPO1 controls redox homeostasis. The capacity of TSPO to bind harmful free heme and porphyrins and scavenge them through autophagy, as shown in Arabidopsis under abiotic stress, seems important to maintenance of the homeostasis required for efficient pathogen defense.
Modelling the past: new generation approaches to understanding biological patterns in the fossil record
Authors: Smith Andrew B. , Barrett Paul M.
Published: November 2011

The history of life on this planet is gleaned from analysing how fossils are distributed through time and space. While these patterns are now rather securely known, at least for well-studied parts of the world, their interpretation remains far from simple. Fossils preserve only partial data from which to reconstruct their biology and the geological record is incomplete and biased, so that taxonomic ranges and palaeocommunity structure are imperfectly known. To better understand the often highly complex deep-time processes that gave rise to the empirical fossil record, palaeontologists have turned to modelling the past. Here, we summarize a series of 11 papers that showcase where modelling the past is being applied to advance our understanding across a wide spectrum of current palaeontological endeavours.
A computational study of the molecular and crystal structure and selected physical properties of octahydridosilasequioxane, (Si
2
O
3
H
2
)
4
. II. Vibrational analysis
Authors: Schutte C. J. H. , Pretorius J. A.
Published: November 2011

A computational study of octahydridosilasequioxane, Si
8
O
12
H
8
, as a free molecule and when embedded in the unit cell
R
-3,
Z
=3, showed that the point group of the free molecule is indeed O
h
, but that its crystal symmetry is reduced to C
3i
. Since the molecular and site-group symmetries influence the vibrational structure of a molecule, a full computational vibrational analysis of the isolated molecule and when embedded in the crystal lattice, is reported here. The analysis of the free molecular spectra given here agrees with that of its experimental infra-red (IR)-spectra and allows the assignment of all the vibrational modes, while the computed phonon dispersion of the crystal confirms the assignment of the internal vibrational modes of the molecule in the crystal. The computed and experimental IR spectra as well as Raman spectra show no indication of serious vibrational intermolecular coupling owing to the presence of multiple molecules in the unit cell. This may be the result of a weak intermolecular vibrational coupling in the solid state, which may feature in the low-frequency modes.
A cooperative virulence plasmid imposes a high fitness cost under conditions that induce pathogenesis
Authors: Platt Thomas G. , Bever James D. , Fuqua Clay
Published: November 2011

Harbouring a plasmid often imposes a fitness cost on the bacterial host. Motivated by implications for public health, the majority of studies on plasmid cost are focused on elements that impart antibiotic resistance. Plasmids, however, can provide a wide range of ecologically important phenotypes to their bacterial hosts—such as virulence, specialized catabolism and metal resistance. TheAgrobacterium tumefacienstumour-inducing (Ti) plasmid confers both the ability to infect dicotyledonous plants and to catabolize the metabolites that plants produce as a result of being infected. We demonstrate that this virulence and catabolic plasmid imposes a measurable fitness cost on host cells under resource-limiting, but not resource replete, environmental conditions. Additionally, we show that the expression of Ti-plasmid-borne pathogenesis genes necessary to initiate cooperative pathogenesis is extremely costly to the host cell. The benefits of agrobacterial pathogenesis stem from the catabolism of public goods produced by infected host plants. Thus, the virulence-plasmid-dependent costs we demonstrate constitute costs of cooperation typically associated with the ability to garner the benefits of cooperation. Interestingly, genotypes that harbour derived opine catabolic plasmids minimize this trade-off, and are thus able to freeload upon the pathogenesis initiated by other individuals.
Horizontal transmission of the insect symbiont
Rickettsia
is plant-mediated
Authors: Caspi-Fluger Ayelet , Inbar Moshe , Mozes-Daube Netta , Katzir Nurit , Portnoy Vitaly , Belausov Eduard , Hunter Martha S. , Zchori-Fein Einat
Published: November 2011

Bacteria in the genus
Rickettsia
, best known as vertebrate pathogens vectored by blood-feeding arthropods, can also be found in phytophagous insects. The presence of closely related bacterial symbionts in evolutionarily distant arthropod hosts presupposes a means of horizontal transmission, but no mechanism for this transmission has been described. Using a combination of experiments with live insects, molecular analyses and microscopy, we found that
Rickettsia
were transferred from an insect host (the whitefly
Bemisia tabaci
) to a plant, moved inside the phloem, and could be acquired by other whiteflies. In one experiment,
Rickettsia
was transferred from the whitefly host to leaves of cotton, basil and black nightshade, where the bacteria were restricted to the phloem cells of the plant. In another experiment,
Rickettsia
-free adult whiteflies, physically segregated but sharing a cotton leaf with
Rickettsia
-plus individuals, acquired the
Rickettsia
at a high rate. Plants can serve as a reservoir for horizontal transmission of
Rickettsia
, a mechanism which may explain the occurrence of phylogenetically similar symbionts among unrelated phytophagous insect species. This plant-mediated transmission route may also exist in other insect–symbiont systems and, since symbionts may play a critical role in the ecology and evolution of their hosts, serve as an immediate and powerful tool for accelerated evolution.
High-resolution mapping of open chromatin in the rice genome
Authors: Zhang Wenli , Wu Yufeng , Schnable James C. , Zeng Zixian , Freeling Michael , Crawford Gregory E. , Jiang Jiming
Published: November 2011

Gene expression is controlled by the complex interaction of transcription factors binding to promoters and other regulatory DNA elements. One common characteristic of the genomic regions associated with regulatory proteins is a pronounced sensitivity to DNase I digestion. We generated genome-wide high-resolution maps of DNase I hypersensitive (DH) sites from both seedling and callus tissues of rice (Oryza sativa). Approximately 25% of the DH sites from both tissues were found in putative promoters, indicating that the vast majority of the gene regulatory elements in rice are not located in promoter regions. We found 58% more DH sites in the callus than in the seedling. For DH sites detected in both the seedling and callus, 31% displayed significantly different levels of DNase I sensitivity within the two tissues. Genes that are differentially expressed in the seedling and callus were frequently associated with DH sites in both tissues. The DNA sequences contained within the DH sites were hypomethylated, consistent with what is known about active gene regulatory elements. Interestingly, tissue-specific DH sites located in the promoters showed a higher level of DNA methylation than the average DNA methylation level of all the DH sites located in the promoters. A distinct elevation of H3K27me3 was associated with intergenic DH sites. These results suggest that epigenetic modifications play a role in the dynamic changes of the numbers and DNase I sensitivity of DH sites during development.
Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis
Authors: Pauli Andrea , Valen Eivind , Lin Michael F. , Garber Manuel , Vastenhouw Nadine L. , Levin Joshua Z. , Fan Lin , Sandelin Albin , Rinn John L. , Regev Aviv , Schier Alexander F.
Published: November 2011

Long noncoding RNAs (lncRNAs) comprise a diverse class of transcripts that structurally resemble mRNAs but do not encode proteins. Recent genome-wide studies in humans and the mouse have annotated lncRNAs expressed in cell lines and adult tissues, but a systematic analysis of lncRNAs expressed during vertebrate embryogenesis has been elusive. To identify lncRNAs with potential functions in vertebrate embryogenesis, we performed a time-series of RNA-seq experiments at eight stages during early zebrafish development. We reconstructed 56,535 high-confidence transcripts in 28,912 loci, recovering the vast majority of expressed RefSeq transcripts while identifying thousands of novel isoforms and expressed loci. We defined a stringent set of 1133 noncoding multi-exonic transcripts expressed during embryogenesis. These include long intergenic ncRNAs (lincRNAs), intronic overlapping lncRNAs, exonic antisense overlapping lncRNAs, and precursors for small RNAs (sRNAs). Zebrafish lncRNAs share many of the characteristics of their mammalian counterparts: relatively short length, low exon number, low expression, and conservation levels comparable to that of introns. Subsets of lncRNAs carry chromatin signatures characteristic of genes with developmental functions. The temporal expression profile of lncRNAs revealed two novel properties: lncRNAs are expressed in narrower time windows than are protein-coding genes and are specifically enriched in early-stage embryos. In addition, several lncRNAs show tissue-specific expression and distinct subcellular localization patterns. Integrative computational analyses associated individual lncRNAs with specific pathways and functions, ranging from cell cycle regulation to morphogenesis. Our study provides the first systematic identification of lncRNAs in a vertebrate embryo and forms the foundation for future genetic, genomic, and evolutionary studies.
Staggered overdose pattern and delay to hospital presentation are associated with adverse outcomes following paracetamol‐induced hepatotoxicity
Authors: Craig Darren G. N. , Bates Caroline M. , Davidson Janice S. , Martin Kirsty G. , Hayes Peter C. , Simpson Kenneth J.
Published: November 2011

WHAT IS ALREADY KNOWN ON THIS SUBJECT

• Paracetamol hepatotoxicity is the commonest cause of acute liver failure (ALF) in the UK.

• Relatively little is known regarding the impact of staggered overdose pattern or delayed hospital presentation upon subsequent mortality or need for emergency liver transplantation.

WHAT THIS STUDY ADDS

• Staggered paracetamol overdoses, frequently taken to relieve pain, are strongly associated with reduced survival compared with single time point overdose.

• Staggered paracetamol overdoses should be treated as high risk for the development of multiorgan failure, and should be considered for N‐acetyl cysteine treatment irrespective of admission serum paracetamol concentrations.

• The King's College poor prognostic criteria may have reduced sensitivity in staggered overdose patients.

AIMS Paracetamol (acetaminophen) poisoning remains the major cause of severe acute hepatotoxicity in the UK. In this large single centre cohort study we examined the clinical impact of staggered overdoses and delayed presentation following paracetamol overdose.

RESULTS Between 1992 and 2008, 663 patients were admitted with paracetamol‐induced severe liver injury, of whom 161 (24.3%) had taken a staggered overdose. Staggered overdose patients were significantly older and more likely to abuse alcohol than single time point overdose patients. Relief of pain (58.2%) was the commonest rationale for repeated supratherapeutic ingestion. Despite lower total ingested paracetamol doses and lower admission serum alanine aminotransferase concentrations, staggered overdose patients were more likely to be encephalopathic on admission, require renal replacement therapy or mechanical ventilation and had higher mortality rates compared with single time point overdoses (37.3% vs. 27.8%, P= 0.025), although this overdose pattern did not independently predict death. The King's College poor prognostic criteria had reduced sensitivity (77.6, 95% CI 70.8, 81.5) for this pattern of overdose. Of the 396/450 (88.0%) single time point overdoses in whom accurate timings could be obtained, 178 (44.9%) presented to medical services >24 h following overdose. Delayed presentation beyond 24 h post overdose was independently associated with death/liver transplantation (OR 2.25, 95% CI 1.23, 4.12, P= 0.009).

CONCLUSIONS Both delayed presentation and staggered overdose pattern are associated with adverse outcomes following paracetamol overdose. These patients are at increased risk of developing multi‐organ failure and should be considered for early transfer to specialist liver centres.
The tumour suppressor FOXO3 is a key regulator of mantle cell lymphoma proliferation and survival
Authors: Obrador‐Hevia Antònia , Serra‐Sitjar Margalida , Rodríguez José , Villalonga Priam , de Mattos Silvia Fernández
Published: November 2011

The FOXO3 (Forkhead/winged helix box class O 3) transcription factor is a crucial regulator of haematopoietic cell fate that controls proliferation and apoptosis, among other processes. Despite the central role of FOXO3 as a tumour suppressor and phosphatidylinositol 3‐kinase (PI3K)/AKT effector, little is known about its involvement in mantle cell lymphoma (MCL) biology. This study investigated the expression and activity of FOXO3 in MCL cell lines and in primary cultures. We analysed the expression of key FOXO regulators and targets, and studied the effect of modulators of FOXO function on cell viability and apoptosis. FOXO3 was constitutively inactivated in MCL cell lines, and showed cytoplasmic localization in patient‐derived cells. PI3K and AKT, but not mammalian target of rapamycin (mTOR), inhibitors induced FOXO3 nuclear translocation and activation in correlation with their impact on MCL proliferation and survival. Moreover, FOXO3‐defective cells were resistant to PI3K/AKT inhibitors. Reactivation of FOXO function with a nuclear export inhibitor had a profound effect on cell viability, consistent with FOXO3 nuclear accumulation. Interestingly, inhibition of FOXO3 nuclear export enhanced the effect of doxorubicin. Taken together, our results confirm that FOXO3 is a relevant regulator of proliferation and apoptosis in MCL, and suggest that reactivation of FOXO3 function might be a useful therapeutic strategy in MCL patients.
Integrating behaviour with life history: boldness of the field cricket, Gryllus integer, during ontogeny
Authors: Niemelä Petri T. , Vainikka Anssi , Hedrick Ann V. , Kortet Raine
Published: November 2011

1. According to a recent hypothesis, personality traits should form integrative pace‐of‐life syndromes with life‐history traits. Potential life‐history traits that explain personality variation are immune defence and growth rate.

2. We studied whether boldness, measured as hiding behaviour, is repeatable during ontogeny in the field cricket, Gryllus integer, and if it relates to the efficiency of immune function (i.e. the capacity to encapsulate a nylon implant), growth rate, developmental time and size as an adult.

3. Hiding behaviour was rank‐order repeatable, and in general, juveniles were bolder than adults. Individuals that were cautious at early juvenile stages had higher encapsulation responses late in life compared with bold individuals. Most clearly, fast‐growing individuals matured early and invested little in immune defence compared with their slower‐growing conspecifics, i.e. showed patterns of a ‘grow fast, die young’ life‐history strategy.

4. Our results may arise from a trade‐off between immunity‐dependent survival and bold behaviour. Trade‐offs between investment in survival and behaviour could account for the maintenance of variation in personality traits by favouring certain combinations of behavioural and life‐history strategies (i.e. pace‐of‐life‐syndromes).
Geographic adaptation in plant–soil mutualisms: tests using Acacia spp. and rhizobial bacteria
Authors: Barrett Luke G. , Broadhurst Linda M. , Thrall Peter H.
Published: November 2011

1. Variation in the effectiveness of mutualistic associations is well characterized in plant–soil symbiont interactions, yet there are little empirical data providing insight into how such variation evolves and persists in natural settings.

2. Heterogeneity in the strength and direction of co‐evolutionary selection among spatially discrete demes is predicted to be important for the maintenance of genetic variation in species interactions. Here, we experimentally test the potential for local adaptation to generate phenotypic divergence among wild host–symbiont populations using two leguminous host species that differ in their specificity for rhizobial partners.

3. Molecular characterization of host populations and associated rhizobial communities revealed significant among‐population genetic differentiation. Reciprocal cross‐inoculation experiments testing for variation in the fitness of nine populations of Acacia salicina and A. stenophylla in response to inoculation with rhizobia revealed variation in host response to the mutualism (both host species), and the benefit conferred by different rhizobial populations (A. salicina only). However, there was no indication that host population‐by‐rhizobial population interactions influence the outcomes of mutualism for the host.

4. We further examined potential correlations between (i) plant response to inoculation and (ii) rhizobial effectiveness, with variation in soil fertility at the sites from which plant and rhizobial samples originated. Data from the cross‐inoculation experiments revealed no correlations between soil chemistry, water availability and either host or rhizobial performance. However, analysis of results from an extensive whole‐soil inoculation trial including nearly 60 A. salicina and A. stenophylla sites showed a significant negative correlation between levels of soil nitrogen and plant response to inoculation.

5. Overall, these findings suggest that selection for local adaptation may play little role in maintaining phenotypic variation in these interactions. We hypothesize that mutualistic interactions occurring among communities of hosts and symbionts do not favour co‐evolutionary divergence among populations.
Flavour of natural and roasted Turkish hazelnut varieties (Corylus avellana L.) by descriptive sensory analysis, electronic nose and chemometrics
Authors: Alasalvar Cesarettin , Pelvan Ebru , Bahar Banu , Korel Figen , Ölmez Hülya
Published: November 2011

A total of eighteen natural and roasted hazelnut varieties (amongst which only Tombul variety is classified as prime quality), grown in the Giresun province of Turkey, were compared for their differences in descriptive sensory analysis (DSA), electronic nose (e‐nose) data and chemometrics. Differences in some descriptive of DSA between natural and roasted hazelnuts as well as within the varieties were observed. Although Tombul hazelnut was selected as one of the best varieties in terms of flavour attributes and received the highest intensities in general, no significant differences (P > 0.05) existed among hazelnut varieties except in certain flavour attributes (‘after taste’ and ‘nutty’). DSA and e‐nose data of natural and roasted hazelnuts were also evaluated for discrimination using principal component analysis (PCA) and cluster analysis. Results of PCA using e‐nose data showed that extracted principal components explained 99.7% and 99.8% of the total variance of the data for natural and roasted hazelnut varieties, respectively. Both DSA and e‐nose can be used for discrimination of natural and roasted hazelnuts.
Starch–methylcellulose–whey protein film properties
Authors: Yoo SeungRan , Krochta John M.
Published: November 2011

Four % (wt/wt) aqueous solutions were prepared at corn starch:methylcellulose:whey protein isolate (CS:MC:WPI) ratios of 2:2:2, 1:2:3, 2:1:3, 2:2:0, 1:2:0 and 2:1:0. Glycerol (gly) was used as a plasticiser at CS–MC–WPI:gly ratios of 2:1, 2.5:1 and 3:1. CS–MC–WPI blend films were stronger than CS–WPI films and had lower oxygen permeability (OP) than MC–WPI films. The highest tensile strength (TS) of blend films was 8.01 ± 3.41 MPa, at CS:MC:WPI ratio of 2:2:0 and CS–MC–WPI:gly ratio of 3:1. Lowest OP value was 45.05 ± 7.24 cm3 μm m−2 per day kPa−1, at CS:MC:WPI ratio of 2:2:2 and CS–MC–WPI:gly ratio of 3:1. OP values were predictable based on relative amounts of components. However, TS and elastic modulus properties of the CS–MC–WPI blend films did not reflect the relative amounts of the components. All of CS–MC–WPI films were translucent indicating some degree of immiscibility among the CS, MC and WPI. These results indicate the influence of complex molecular interactions among the components.
Adsorption behaviour of some anthocyanins by wheat gluten and its fractions in acidic conditions
Authors: Mazzaracchio Palmira , Kindt Maddalena , Pifferi Pier G. , Tozzi Silvia , Barbiroli Giancarlo
Published: November 2011

Some anthocyanins, both commercial delphinidin‐3‐O‐β‐d‐glucoside chloride and cyanidin‐3‐O‐β‐d‐rutinoside chloride (Dp3glu and Cy3rut) and extracted from plants, were adsorbed by gluten or its fractions to carry out a study that can be considered a premise to estimate the potential effect on bioavailability of anthocyanin adsorption. This process was studied by means of adsorption kinetics and isotherms. Among the parameters determining adsorption, the temperature and the pH value were evaluated. The data show that gluten and its fraction have a great adsorption capacity (about 1.0 mg g−1 of gluten). The results indicate that the structure of the anthocyanins plays an important role in their adsorption by gluten or its fractions; in fact, the adsorption kinetics show that Dp3glu is more adsorbed than Cy3rut. The isotherms of anthocyanin adsorption by gluten indicate the presence of a strong interaction between the two types of molecules. This could be an important finding to obtain functionalised‐based gluten products.
Baseline medication adherence and blood pressure in a 24‐month longitudinal hypertension study
Authors: Shaw Ryan , Bosworth Hayden B
Published: November 2011

Aim and objectives.  We sought to identify the feasibility and predictive validity of an easy and quick self‐reported measure of medication adherence and to identify characteristics of people with hypertension that may warrant increase attentiveness by nurses to address hypertensive self‐management needs.

Background.  Current control rates of hypertension are approximately 50%. Effective blood pressure control can be achieved in most people with hypertension through antihypertensive medication. However, hypertension control can only be achieved if the patient is adherent with their medication regimen. Patients who are non‐adherent may be in need of additional intervention.

Design.  This secondary analysis evaluated the systolic blood pressure of patients who received usual hypertension management across 24 months at six‐month intervals.

Methods.  A longitudinal study of 159 hypertensive patients in two primary care clinics.

Results.  In a sample of 159 patients receiving care in a primary care facility, baseline medication non‐adherence was associated with a 6·3 mmHg increase in systolic blood pressure (p < 0·05) at baseline, a 8·4 mmHg increase in systolic blood pressure (p < 0·05) at 12 months and a 7·5 increase in systolic blood pressure at 24 months (p < 0·05) compared with adherent patients, respectively. Results also indicate a significant increase in systolic blood pressure across 24 months among people who identified as minority and of low financial status.

Conclusions.  Non‐adherence with antihypertensive medication at baseline was predictive of increased systolic blood pressure up to 24 months postbaseline.

Relevance to clinical practice.  This study demonstrates the use of an easy‐to‐use questionnaire to identify patients who are non‐adherent. We recommend assessing medication adherence to identify patients who are non‐adherent with their anti‐hypertensive medication and to be especially vigilant with patients who are minority or are considered low income.
Working in the real world: a review of sociological concepts of health and well‐being and their relation to modern mental health nursing
Authors: BLAKEMAN P. , FORD L.
Published: November 2011

Accessible summary

Large gaps in income between the rich and poor seem to be related to poor mental health, but the explanations are not always simple.

Some people are more able than others to withstand the pressures generated by these large gaps, and some explanations for why are given.

Nurses can help people who are affected by these gaps become more resilient and develop ways to live fuller and richer lives.

Nurses are also well placed to lead this change as many of the ideas are familiar to them.

Since 2008, the world has witnessed several socio‐economic upheavals that have fundamentally changed the global economy. Within the UK, these upheavals have coincided with a change in political administration and thus a new approach to managing the volatility of economy. This change has resulted in root and branch reform of service provision that is based around a model that incorporates a shrinking public sector coupled with an increase in civic participation (i.e. ‘The Big Society’ espoused by the UK‐governing coalition). It is also unlikely that healthcare provision on a global level will remain unchanged in such turbulent times. It would therefore seem a useful time to review how socio‐economic forces are believed to affect the health and well‐being of an individual. These forces include social inequality, the mechanisms of social inclusion and exclusion, social role and the erosion of resilience. This paper will then conclude by offering some potential avenues that nurses can explore to make these forces less damaging for their clients. These avenues include developing a clinical focus based around positive psychology, well‐being and some novel ways that nurses can help overcome the maintenance cycles that perpetuate inequality and exclusion.
The rice geneDEFECTIVE TAPETUM AND MEIOCYTES 1(DTM1) is required for early tapetum development and meiosis
Authors: Yi Jakyung , Kim Sung‐Ryul , Lee Dong‐Yeon , Moon Sunok , Lee Yang‐Seok , Jung Ki‐Hong , Hwang Inhwan , An Gynheung
Published: November 2011

Tapetum development and meiosis play crucial roles in anther development. Here we identified a rice gene,DEFECTIVE TAPETUM AND MEIOCYTES 1(DTM1), which controls the early stages of that development. This gene encodes for an endoplasmic reticulum (ER) membrane protein that is present only in cereals. Our T‐DNA insertion mutations gave rise to abnormal tapetal formation. Cellular organelles, especially the ER, were underdeveloped, which led to hampered differentiation and degeneration of the tapetum. In addition, the development of pollen mother cells was arrested at the early stages of meiotic prophase I. RNAin‐situhybridization analyses showed thatDTM1transcripts were most abundant in tapetal cells at stages 6 and 7, and moderately in the pollen mother cells and meiocytes. Transcripts ofUDT1,which functions in tapetum development during early meiosis, were reduced indtm1anthers, as were those ofPAIR1, which is involved in chromosome pairing and synapsis during meiosis. However, expression ofMSP1andMEL1, which function in anther wall specification and germ cell division, respectively, was not altered in thedtm1mutant. Moreover, transcripts ofDTM1were reduced inmsp1mutant anthers, but not inudt1andpair1mutants. These results, together with their mutant phenotypes, suggest that DTM1 plays important roles in the ER membrane during early tapetum development, functioning afterMSP1and beforeUDT1, and also in meiocyte development, afterMEL1and beforePAIR1.
The Role of Trait Anger in the Relationship between Stressors and Counterproductive Work Behaviors: Convergent Findings from Multiple Studies and Methodologies
Authors: Ilie Alexandra , Penney Lisa M. , Ispas Dan , Iliescu Dragos
Published: November 2011

Across three studies, we investigated the moderating role of trait anger in the relationship between workplace stressors and counterproductive work behaviors (CWB). In Study 1, all the variables were measured using self‐reports. In Study 2, workplace stressors were measured using co‐worker reports, trait anger was measured using significant other reports, and CWB was measured using self‐reports. In Study 3, we measured workplace stressors at Time 1, trait anger at Time 2 (6 months later), and objective indicators of CWB at Time 3 (12 months after Time 2). Convergent results were obtained across the three studies, with positive associations between workplace stressors and CWB, trait anger and CWB, and with trait anger moderating the relationship between stressors and CWB.