bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide identification of TAL1's functional targets: Insights into its mechanisms of action in primary erythroid cells
Authors: Kassouf Mira T. , Hughes Jim R. , Taylor Stephen , McGowan Simon J. , Soneji Shamit , Green Angela L. , Vyas Paresh , Porcher Catherine
Published: June 2010

Coordination of cellular processes through the establishment of tissue-specific gene expression programs is essential for lineage maturation. The basic helix-loop-helix hemopoietic transcriptional regulator TAL1 (formerly SCL) is required for terminal differentiation of red blood cells. To gain insight into TAL1 function and mechanisms of action in erythropoiesis, we performed ChIP-sequencing and gene expression analyses from primary fetal liver erythroid cells. We show that TAL1 coordinates expression of genes in most known red cell–specific processes. The majority of TAL1's genomic targets require direct DNA-binding activity. However, one-fifth of TAL1's target sequences, mainly among those showing high affinity for TAL1, can recruit the factor independently of its DNA binding activity. An unbiased DNA motif search of sequences bound by TAL1 identified CAGNTG as TAL1-preferred E-box motif in erythroid cells. Novel motifs were also characterized that may help distinguish activated from repressed genes and suggest a new mechanism by which TAL1 may be recruited to DNA. Finally, analysis of recruitment of GATA1, a protein partner of TAL1, to sequences occupied by TAL1 suggests that TAL1's binding is necessary prior or simultaneous to that of GATA1. This work provides the framework to study regulatory networks leading to erythroid terminal maturation and to model mechanisms of action of tissue-specific transcription factors.
Unidirectional growth ofL-cysteine hydrochloride monohydrate: first time observation as nonlinear optical material and its characterization
Authors: Bhagavannarayana G. , Kumar Suman , Shakir Mohd , Kushawaha S. K. , Maurya K. K. , Malhotra Rajni , Rao K. Ramachandra
Published: June 2010

A bulk size (∼60 mm length and 20 mm diameter) single crystal of L-cysteine hydrochloride monohydrate has been successfully grown for the first time by the unidirectional Sankaranarayanan–Ramasamy method and found to be a nonlinear optical material by observing the second harmonic generation (SHG). The crystal structure has been confirmed by single-crystal as well as powder X-ray diffraction analysis. The Fourier transform–Raman technique was used to study the vibrational modes and functional groups. The grown crystal was found to be highly transparent. The crystalline perfection has been evaluated by high-resolution X-ray diffractometry and the grown crystal was found to be free from macroscopic defects such as structural grain boundaries. The relative SHG efficiency and laser damage threshold values were found to be 1.2 and 5.5 times that of a potassium dihydrogen phosphate crystal, respectively. The dielectric constant, dielectric loss and alternating current conductivity were measured by an impedance analyser over a wide range of frequency between 100 Hz and 5 MHz. The dielectric constant was found to be stable for the entire range of frequency with very small dielectric loss, making this material suitable for device applications. The present investigation reveals that the title compound, since it can be grown with desirable size along a predetermined direction and it is a good nonlinear optical material with the prerequisite optical and dielectric properties, is a good candidate for photonic or opto-electronic applications.
Structure determination of the minimal complex between Tfb5 and Tfb2, two subunits of the yeast transcription/DNA-repair factor TFIIH: a retrospective study
Authors: Kainov Denis E. , Cura Vincent , Vitorino Marc , Nierengarten Helène , Poussin Pierre , Kieffer Bruno , Cavarelli Jean , Poterszman Arnaud
Published: June 2010

Tfb5 interacts with the Tfb2 subunit of the general transcription factor TFIIH to ensure efficient nucleotide-excision repair in eukaryotes. The crystal structure of the complex between Tfb5 and the C-terminal region of Tfb2 (Tfb2C) fromSaccharomyces cerevisiaehas recently been reported. Here, the structure-determination process is described as a case study. Although crystals were obtained readily, it was not possible to determine experimental phases from a first crystal form (Tfb2412–513–Tfb52–72) that diffracted to 2.6 Å resolution. Shortening of the Tfb2C from its N-terminus was decisive and modified the crystal packing, leading to a second crystal form (Tfb2435–513–Tfb52–72). These crystals diffracted to 1.7 Å resolution with excellent mosaicity and allowed structure determination by conventional approaches using heavy atoms. The refined structure from the second crystal form was used to solve the structure of the first crystal form by molecular replacement. Comparison of the two structures revealed that the N-terminal region of Tfb2C and (to a lesser extent) the C-terminal region of Tfb5 contributed to the crystal packing. A detailed analysis illustrates how variation in domain boundaries influences crystal packing and quality.
Structures of apo and GTP-bound molybdenum cofactor biosynthesis protein MoaC fromThermus thermophilusHB8
Authors: Kanaujia Shankar Prasad , Jeyakanthan Jeyaraman , Nakagawa Noriko , Balasubramaniam Sathyaramya , Shinkai Akeo , Kuramitsu Seiki , Yokoyama Shigeyuki , Sekar Kanagaraj
Published: June 2010

The first step in the molybdenum cofactor (Moco) biosynthesis pathway involves the conversion of guanosine triphosphate (GTP) to precursor Z by two proteins (MoaA and MoaC). MoaA belongs to theS-adenosylmethionine-dependent radical enzyme superfamily and is believed to generate protein and/or substrate radicals by reductive cleavage ofS-adenosylmethionine using an Fe–S cluster. MoaC has been suggested to catalyze the release of pyrophosphate and the formation of the cyclic phosphate of precursor Z. However, structural evidence showing the binding of a substrate-like molecule to MoaC is not available. Here, apo and GTP-bound crystal structures of MoaC fromThermus thermophilusHB8 are reported. Furthermore, isothermal titration calorimetry experiments have been carried out in order to obtain thermodynamic parameters for the protein–ligand interactions. In addition, molecular-dynamics (MD) simulations have been carried out on the protein–ligand complex of known structure and on models of relevant complexes for which X-ray structures are not available. The biophysical, structural and MD results reveal the residues that are involved in substrate binding and help in speculating upon a possible mechanism.
Intervention and strategy analysis for web group‐learning
Authors: Chen G.D. , Ou K.L. , Liu C.C. , Liu B.J.
Published: June 2010

Abstract Owing to the lack of face‐to‐face interactions, students using a web‐based learning system are likely to study alone and with relatively little classmate support and pressure. Teachers in a web‐based learning system may apply a group‐learning model to overcome this problem. Teachers first need to organise, manage and monitor the group learning and they must take appropriate actions based on teaching strategies to improve the learning achievements of the students. To perform these tasks effectively, teachers must obtain relevant information by analysing the huge volume of web‐access logs or by monitoring web interactions. This paper presents novel methodologies for developing instruments to assist teachers in performing intervention and strategy analysis. The proposed methodologies apply data mining tools provided by existing database management systems. Database techniques, including the multi‐dimensional cube, are then applied to make student web logs meaningful and helpful to teachers in managing group learning. The associate rule mining tool is finally employed to assist teachers in analysing their pedagogical strategies. These tools relieve teachers of tedious data collection and analysis, allowing them to focus on managing the groups to promote students' learning achievement.
Ficus racemosa is pollinated by a single population of a single agaonid wasp species in continental South‐East Asia
Authors: KOBMOO N. , HOSSAERT‐MCKEY M. , RASPLUS J. Y. , KJELLBERG F.
Published: June 2010

High specificity in the Ficus‐agaonid wasp mutualism has lead to the assumption of a mostly ‘one‐to‐one’ relationship, albeit with some exceptions. This view has been challenged by new molecular data in recent years, but surprisingly little is known about local and spatial genetic structuring of agaonid wasp populations. Using microsatellite markers, we analysed genetic structuring of Ceratosolen fusciceps, the fig wasp pollinating Ficus racemosa, a fig tree species widely distributed from India to Australia. In sampling stretching from the south of China to the south of Thailand we found evidence for only a single pollinating wasp species in continental South‐East Asian mainland. We found no evidence for the co‐occurrence of cryptic species within our subcontinent sampling zone. We observed no spatial genetic structure within sites and only limited structuring over the whole sampling zone, suggesting that F. racemosa is pollinated by a single population of a single agaonid wasp species all over continental South‐East Asia. An additional sample of wasps collected on F. racemosa in Australia showed clear‐cut genetic differentiation from the Asian continent, suggesting allopatric divergence into subspecies or species. We propose that the frequent local co‐occurrence of sister species found in the literature mainly stems from contact zones between biogeographic regions, and that a single pollinator species over wide areas might be the more common situation everywhere else.
Macrogeographic population structuring in the cosmopolitan agricultural pest Bactrocera cucurbitae (Diptera: Tephritidae)
Authors: VIRGILIO M. , DELATTE H. , BACKELJAU T. , DE MEYER M.
Published: June 2010

The macrogeographic population structure of the agricultural pest Bactrocera cucurbitae (Diptera: Tephritidae) was investigated in order to identify the geographic origin of the species and reconstruct its range expansion. Individuals of B. cucurbitae were collected from 25 worldwide‐distributed localities (n = 570) and genotyped at 13 microsatellite loci. The Bayesian clustering reveals that B. cucurbitae can be subdivided into five main groups corresponding to populations from (i) the African continent, (ii) La Réunion, (iii) Central Asia, (iv) East Asia and (v) Hawaii. The proportions of inter‐regional assignments and the higher values of genetic diversity in populations from Pakistan, India and Bangladesh suggest that B. cucurbitae originated in Central Asia and expanded its range to East Asia and Hawaii on one hand and to Africa and the islands of the Indian Ocean on the other. A number of outliers (10–19 specimens according to different clustering algorithms) show high levels of admixture (Q > 0.70) with populations from different regions and reveal complex patterns of inter‐regional gene flow. Anthropogenic transport is the most plausible promoter of this large‐scale dispersal. The introduction of individuals from geographically distant sources did not have a relevant role in the most recent African invasions, which originated from the expansion of local populations. These results could provide a useful background to better evaluate invasion risks and establish priorities for the management of this cosmopolitan agricultural pest.
Structure‐function analysis of npr1 alleles in Arabidopsis reveals a role for its paralogs in the perception of salicylic acid
Authors: CANET JUAN VICENTE , DOBÓN ALBOR , ROIG ALEJANDRA , TORNERO PABLO
Published: June 2010

Salicylic acid (SA) is necessary for plant defence against some pathogens, whereas NPR1 is necessary for SA perception. Plant defence can be induced to an extreme by several applications of benzothiadiazole (BTH), an analogue of SA. Thus, plants that do not perceive BTH grow unaffected, whereas wild‐type plants grow stunted. This feature allows us to screen for mutants in Arabidopsis thaliana that show insensitivity to BTH in a high‐throughput fashion. Most of the mutants are npr1 alleles, with similar phenotypes in plant weight and pathogen growth. The mutations are clustered in the carboxyl‐terminal part of the protein, and no obvious null alleles were recovered. These facts have prompted a search for knockouts in the NPR1 gene. Two of these KO alleles identified are null and have an intermediate phenotype. All the evidence presented lead us to propose a redundancy in SA perception, with the paralogs of NPR1 taking part in this signalling. We show that the mutations recovered in the screening genetically interact with the paralogs preventing their function in SA signalling.
Can the progressive increase of C4 bundle sheath leakiness at low PFD be explained by incomplete suppression of photorespiration?
Authors: KROMDIJK JOHANNES , GRIFFITHS HOWARD , SCHEPERS HANS E.
Published: June 2010

The ability to concentrate CO2 around Rubisco allows C4 crops to suppress photorespiration. However, as phosphoenolpyruvate regeneration requires ATP, the energetic efficiency of the C4 pathway at low photosynthetic flux densities (PFD) becomes a balancing act between primary fixation and concentration of CO2 in mesophyll (M) cells, and CO2 reduction in bundle sheath (BS) cells. At low PFD, retro‐diffusion of CO2 from BS cells, relative to the rate of bicarbonate fixation in M cells (termed leakiness φ), is known to increase. This paper investigates whether this increase in ϕ could be explained by incomplete inhibition of photorespiration.

The PFD response of φ was measured at various O2 partial pressures in young Zea mays plants grown at 250 (LL) and 750 µmol m−2 s−1 PFD (HL). φ increased at low PFD and was positively correlated with O2 partial pressure. Low PFD during growth caused BS conductance and interveinal distance to be lower in the LL plants, compared to the HL plants, which correlated with lower φ. Model analysis showed that incomplete inhibition of photorespiration, especially in the HL plants, and an increase in the relative contribution of mitochondrial respiration at low PFD could explain the observed increases in φ.
Continuous glucose monitoring by intravenous microdialysis
Authors: ROOYACKERS O. , BLIXT C. , MATTSSON P. , WERNERMAN J.
Published: June 2010

Background: The conflicting results from studies over tight glucose control in intensive care unit (ICU) patients ask for a continuous on‐line real‐time glucose monitoring in future. Here, intravenous microdialysis was tested in ICU patients and healthy volunteers. Primary aims were technical feasibility and accuracy.

Methods: A microdialysis catheter was inserted into a peripheral vein. ICU patients (n=10) were studied for up to 5 days. Healthy volunteers (n=6) were studied on one occasion. Recordings were monitored during 70 min each 24‐h period to allow for an estimate of variability over time. Microdialysis glucose and lactate were compared with plasma glucose and whole blood lactate. Results are presented as medians (quartiles) of the differences between microdialysis and plasma concentrations over each of the 70‐min recording periods.

Results: Out of the included ICU patients, no exclusions or early terminations were due to failure of the microdialysis catheter. The concordance was highly variable. The difference of medians over the recording periods differed by −34% (−40, −16) in patients and −22% (−31, −15) for the volunteers. In contrast, the overall variability within the individual measurement periods was low.

Conclusion: Technical feasibility was good, but the accuracy was not sufficient and the variability between the recording periods was high without calibrations. The non‐availability of suitable peripheral veins was a problem in many patients screened but not included in the study. Intravenous microdialysis to obtain continuous on‐line real‐time glucose monitoring is technically feasible, but accuracy needs to be improved.
DROUGHT STRESS: Physiological Basis for Genotypic Variation in Tolerance to and Recovery from Pre‐flowering Drought in Peanut
Authors: Puangbut D. , Jogloy S. , Toomsan B. , Vorasoot N. , Akkasaeng C. , Kesmala T. , Rachaputi R. C. N. , Wright G. C. , Patanothai A.
Published: June 2010

Drought during the pre‐flowering stage can increase yield of peanut. There is limited information on genotypic variation for tolerance to and recovery from pre‐flowering drought (PFD) and more importantly the physiological traits underlying genotypic variation. The objectives of this study were to determine the effects of moisture stress during the pre‐flowering phase on pod yield and to understand some of the physiological responses underlying genotypic variation in response to and recovery from PFD. A glasshouse and field experiments were conducted at Khon Kaen University, Thailand. The glasshouse experiment was a randomized complete block design consisting of two watering regimes, i.e. fully‐irrigated control and 1/3 available soil water from emergence to 40 days after emergence followed by adequate water supply, and 12 peanut genotypes. The field experiment was a split‐plot design with two watering regimes as main‐plots, and 12 peanut genotypes as sub‐plots. Measurements of N2 fixation, leaf area (LA) were made in both experiments. In addition, root growth was measured in the glasshouse experiment. Imposition of PFD followed by recovery resulted in an average increase in yield of 24 % (range from 10 % to 57 %) and 12 % (range from 2 % to 51 %) in the field and glasshouse experiments, respectively. Significant genotypic variation for N2 fixation, LA and root growth was also observed after recovery. The study revealed that recovery growth following release of PFD had a stronger influence on final yield than tolerance to water deficits during the PFD. A combination of N2 fixation, LA and root growth accounted for a major portion of the genotypic variation in yield (r = 0.68–0.93) suggesting that these traits could be used as selection criteria for identifying genotypes with rapid recovery from PFD. A combined analysis of glasshouse and field experiments showed that LA and N2 fixation during the recovery had low genotype × environment interaction indicating potential for using these traits for selecting genotypes in peanut improvement programs.
SHORT COMMUNICATION: Effect of Salt Stress on Peruvian Germplasm of Chenopodium quinoa Willd.: A Promising Crop
Authors: Gómez‐Pando L. R. , Álvarez‐Castro R. , Eguiluz‐de la Barra A.
Published: June 2010

Soil salinity is a major problem in today’s agriculture. Quinoa has become an important crop because it exhibits high levels of salinity tolerance. In addition, its seeds contain an excellent balance of carbohydrates, lipids, amino acids and proteins for human nutrition. The quinoa germplasm includes almost 2500 accessions, some of which have been tested under salt stress. Here, we report the effect of NaCl on the germination of 182 previously untested accessions. When seeds were irrigated with saline water at 30 dS m−1 EC, the stress appeared to be too high: all accessions showed less than 60 % germination. In contrast, irrigation with 25 dS m−1 EC saline water allowed over 60 % germination in 15 accessions. These latter accessions’ agricultural traits were then evaluated. The overall coefficients of variation indicated that quinoa genotype and salt treatment dramatically influence root dry mass per plant, but do not noticeably affect the length of the plant’s life cycle. Unexpectedly, salt treatment resulted in increased plant height, leaf dry mass and grain yield. Using Euclidean distance for the simultaneous selection of these five agricultural traits, accessions 100, 136, 127 and 105 proved to be the best performing genotypes under salt stress.
The Effect of Mulching, Tillage and Rotation on Yield in Non‐flooded Compared with Flooded Rice Production
Authors: Qin J. , Hu F. , Li D. , Li H. , Lu J. , Yu R.
Published: June 2010

Non‐flooded rice cultivation has been proven to be an effective measure to reduce water consumption in drought areas of Southeast China. However, rice cultivation under non‐flooded conditions leads to less stable productivity and lower grain yield. The objectives of this study were (1) to compare crop performance and yields among flooded and non‐flooded rice over several seasons, (2) to identify the yield performed in non‐flooded rice systems over seasons and whether the options which included no‐tillage, straw mulching and wet‐dry rotation system can narrow the grain yield gap between non‐flooded and traditional flooded condition. The results showed the difference between flooded rice (F) and non‐flooded rice (NF) with straw mulching was much lower than the difference between F and NF without straw mulching. Within late seasons, the difference of aboveground total biomass between non‐flooded rice without mulching and flooded rice gradually widened as the number of cropping seasons increased. Compared with the non‐flooded rice without mulching, straw mulching can reduce the decline of aboveground total biomass and grain yield. The yield difference between F and NF treatments became smaller in no‐tillage plots than complete tillage plots. It suggested that no‐tillage can keep the crop production more stable. In comparison with continuously non‐flooded cultivation, our study indicated that the wet‐dry rotation system can reduce the yield decline under non‐flooded condition.
Changes in Hormonal Balance: A Possible Mechanism of Pre‐Sowing Chilling‐Induced Salt Tolerance in Spring Wheat
Authors: Iqbal M. , Ashraf M.
Published: June 2010

There is a lack of knowledge about factors contributing to the chilling‐induced alleviatory effects on growth of plants under salt stress. Thus, the primary objective of the study was to determine whether chilling‐induced changes in endogenous hormones, ionic partitioning within shoots and roots and/or gaseous exchange characteristics is involved in salt tolerance of two genetically diverses of wheat crops. For this purpose, the seeds of two spring wheat (Triticum aestivum) cultivars, MH‐97 (salt intolerant) and Inqlab‐91 (salt tolerant) were chilled at 3°C for 2 weeks. The chilled, hydroprimed and non‐primed (control) seeds of the two wheat cultivars were sown in both Petri dishes in a growth room and in the field after treatment with 15 dS m−1 NaCl salinity. Chilling was very effective in increasing germination rate and subsequent growth when compared with hydropriming and control under salt stress. Results from field experiments clearly indicated the efficacy of chilling over hydropriming in improving shoot dry biomass and grain yield in either cultivar, particularly under salt stress. This increase in growth and yield was related to increased net photosynthetic rate, greater potential to uptake and accumulate the beneficial mineral elements (K+ and Ca2+) in the roots and reduced uptake and accumulation of toxic mineral element (Na+) in the shoots of both wheat cultivars when grown under salt stress. Salt‐stressed plants of both wheat cultivars raised from chilled seed had greater concentrations of indoleacetic acid, abscisic acid, salicylic acid and spermine when compared with hydropriming and control. Therefore, induction of salt tolerance by pre‐sowing chilling treatment in wheat could be attributed to its beneficial effects on ionic homeostasis and hormonal balance. The results presented are also helpful to understand the chilling‐induced cross adaptation of plants in natural environments. Moreover, efficacy of pre‐sowing chilling treatment over hydropriming suggested its commercial utilization as a low risk priming treatment for better wheat crop production under stressful environments.
Interaction of hydrogen sulfide with ion channels
Authors: Tang Guanghua , Wu Lingyun , Wang Rui
Published: June 2010

1. Hydrogen sulfide (H2S) is a signalling gasotransmitter. It targets different ion channels and receptors, and fulfils its various roles in modulating the functions of different systems. However, the interaction of H2S with different types of ion channels and underlying molecular mechanisms has not been reviewed systematically.

2. H2S is the first identified endogenous gaseous opener of ATP‐sensitive K+channels in vascular smooth muscle cells. Through the activation of ATP‐sensitive K+channels, H2S lowers blood pressure, protects the heart from ischemia and reperfusion injury, inhibits insulin secretion in pancreatic β cells, and exerts anti‐inflammatory, anti‐nociceptive and anti‐apoptotic effects.

3. H2S inhibited L‐type Ca2+channels in cardiomyocytes but stimulated the same channels in neurons, thus regulating intracellular Ca2+levels. H2S activated small and medium conductance KCachannels but its effect on BKCachannels has not been consistent.

4. H2S‐induced hyperalgesia and pro‐nociception seems to be related to the sensitization of both T‐type Ca2+channels and TRPV1channels. The activation of TRPV1and TRPA1by H2S is believed to result in contraction of nonvascular smooth muscles and increased colonic mucosal Cl−secretion.

5. The activation of Cl−channel by H2S has been shown as a protective mechanism for neurons from oxytosis. H2S also potentiatesN‐methyl‐d‐aspartic acid receptor‐mediated currents that are involved in regulating synaptic plasticity for learning and memory.

6. Given the important modulatory effects of H2S on different ion channels, many cellular functions and disease conditions related to homeostatic control of ion fluxes across cell membrane should be re‐evaluated.
High glucose induces apoptosis in AC16 human cardiomyocytes via macrophage migration inhibitory factor and c‐Jun N‐terminal kinase
Authors: Liang Jia‐Liang , Xiao Ding‐Zhang , Liu Xiao‐Ying , Lin Qiu‐Xiong , Shan Zhi‐Xin , Zhu Jie‐Ning , Lin Shu‐Guang , Yu Xi‐Yong
Published: June 2010

1. It is known that high glucose can induce cardiomyocyte apoptosis and that macrophage migration inhibitory factor (MIF) may be involved in the development of diabetes. However, the relationship between high glucose and MIF in diabetic cardiomyopathy remains unclear.

2. In the present study, AC16 human cardiomyocytes were cultured in the presence of 25 mmol/L glucose for 20, 30 and 60 min before being subjected to western blot analyses to determine MIF expression and c‐Jun N‐terminal kinase (JNK) activation. In addition, AC16 cells were pretreated with 2.5 μmol/L SP600125 (a JNK inhibitor), 40 μmol/L (s,r)‐3‐(4‐hydroxyphenyl)‐4,5‐dihydro‐5‐isoxazole acetic acid methyl ester (ISO‐1; an MIF antagonist) or 0.1% dimethylsulphoxide (DMSO; vehicle) for 1 h prior to exposure to 25 mmol/L glucose and culture for 72 h, followed by annexin V–fluorescein isothiocyanate/propidium iodide staining and flow cytometry analysis. Caspase 3 activity and phosphorylation of JNK were also analysed by western blotting.

3. The high concentration of glucose increased expression of endogenous MIF and JNK phosphorylation in AC16 cardiomyocytes. Pretreatment of cells with SP600125 and ISO‐1 reduced glucose‐induced apoptosis and caspase 3 activity. Furthermore, JNK phosphorylation was attenuated by inhibition of endogenous MIF.

4. In conclusion, myocardial cell apoptosis induced by high glucose involves the overexpression of MIF and activation of the JNK signalling pathway. The identification of a high glucose–MIF–JNK pathway will help determine potential new targets in the treatment of diabetic cardiomyopathy.
Adenosine A1and A2Areceptors are not upstream of caffeine’s dopamine D2receptor‐dependent aversive effects and dopamine‐independent rewarding effects
Authors: Sturgess Jessica E. , Ting‐A‐Kee Ryan A. , Podbielski Dominik , Sellings Laurie H. L. , Chen Jiang‐Fan , Van Der Kooy Derek
Published: June 2010

Caffeine is widely consumed throughout the world, but little is known about the mechanisms underlying its rewarding and aversive properties. We show that pharmacological antagonism of dopamine not only blocks conditioned place aversion to caffeine, but also reveals dopamine blockade‐induced conditioned place preferences. These aversive effects are mediated by the dopamine D2receptor, as knockout mice showed conditioned place preferences in response to doses of caffeine that C57Bl/6 mice found aversive. Furthermore, these aversive responses appear to be centrally mediated, as a quaternary analog of caffeine failed to produce conditioned place aversion. Although the adenosine A2Areceptor is important for caffeine’s physiological effects, this receptor seems only to modulate the appetitive and aversive effects of caffeine. A2Areceptor knockout mice showed stronger dopamine‐dependent aversive responses to caffeine than did C57Bl/6 mice, which partially obscured the dopamine‐independent and A2Areceptor‐independent preferences. Additionally, the A1receptor, alone or in combination with the A2Areceptor, does not seem to be important for caffeine’s rewarding or aversive effects. Finally, excitotoxic lesions of the tegmental pedunculopontine nucleus revealed that this brain region is not involved in dopamine blockade‐induced caffeine reward. These data provide surprising new information on the mechanism of action of caffeine, indicating that adenosine receptors do not mediate caffeine’s appetitive and aversive effects. We show that caffeine has an atypical reward mechanism, independent of the dopaminergic system and the tegmental pedunculopontine nucleus, and provide additional evidence in support of a role for the dopaminergic system in aversive learning.
The metavirome of a hypersaline environment
Authors: Santos Fernando , Yarza Pablo , Parro Víctor , Briones Carlos , Antón Josefa
Published: June 2010

Hypersaline environments harbour the highest number of virus‐like particles reported for planktonic systems. However, very little is known about the genomic diversity of these virus assemblages since most of the knowledge on halophages is based on the analysis of a few isolates infecting strains of hyperhalophilic Archaea that may not be representatives of the natural microbiota. Here, we report the characterization, through a metagenomic approach, of the viral assemblage inhabiting a crystallizer pond (CR30) from a multi‐pond solar saltern in Santa Pola (SE Spain). A total of 1.35 Mbp were cloned that yielded a total of 620 kb sequenced viral DNA. The metavirome was highly diverse and different from virus communities of marine and other aquatic environments although it showed some similarities with metaviromes from high‐salt ponds in solar salterns in San Diego (SW USA), indicating some common traits between high‐salt viromes. A high degree of diversity was found in the halophages as revealed by the presence of 2479 polymorphic nucleotides. Dinucleotide frequency analysis of the CR30 metavirome showed a good correlation with GC content and enabled the establishment of different groups, and even the assignment of their putative hosts: the archaeon Haloquadratum walsbyi and the bacterium Salinibacter ruber.
Editorial Board Membership of Management and Business Journals: A Social Network Analysis Study of the Financial Times 40
Authors: Burgess Thomas F. , Shaw Nicola E.
Published: June 2010

We apply social network analysis to editorial board membership data for 36 of the 40 high‐ranking journals forming theFinancial Timeslist for grading business schools. Data are presented by individuals, journals, organizations and countries. Using cluster analysis and multidimensional scaling, journals are allocated to academic fields. Distributions of journals, editorial board members and business school staff by field are compared. Academics affiliated to US organizations predominate and highly ranked US organizations occupy the top positions for number of board memberships. Academics with high multiple board memberships come from a more diverse set of organizations but are still predominantly North American and male. We suggest that the domination of the sampled journal production system by special interest groups could permit academic patronage to prosper. We characterize the academic area of management (and business) as a loosely connected grouping of mono‐disciplinary fields. Organization behaviour, strategy and enterprise/small business fields are over‐represented in theFinancial Timeslist while accounting, finance, marketing and operations research/management information systems are under‐represented. We argue that domination by an elite and its fragmented mono‐disciplinarity is not healthy for the management academic area.
Poverty in Edwardian Britain
Authors: GAZELEY IAN , NEWELL ANDREW
Published: June 2010

This article introduces a newly discovered household budget data set for 1904. We use these data to estimate urban poverty among working families in the British Isles. Applying Bowley's poverty line, we estimate that at least 23 per cent of people in urban working households and 18 per cent of working households had income insufficient to meet minimum needs. This is well above Rowntree's estimate of primary poverty for York in 1899 and high in the range that Bowley found in northern towns in 1912–13. The skill gradient of poverty is steep; for instance, among labourers' households, the poverty rates are close to 50 per cent. Measures of the depth of poverty are relatively low in the data, suggesting that most poor male‐headed working households were close to meeting Bowley's new standard.
Who comprised the nation of shareholders? Gender and investment in Great Britain, c. 1870–1935
Authors: RUTTERFORD JANETTE , GREEN DAVID R. , MALTBY JOSEPHINE , OWENS ALASTAIR
Published: June 2010

This article explores the widening ownership of stocks and shares in Great Britain between 1870 and 1935. It demonstrates the extent of that growth and the increasing number of small investors. Women became more important in terms of the number of shareholders and value of holdings. Factors that encouraged this trend included the issue of less risky types of investments, and legal changes relating to married women's property. We examine the ‘deepening’ importance of stocks and shares for wealth holders, arguing that the growing significance of these kinds of financial assets was as important as the growth in the investor population.
Immunophenotyping of inflammatory cells in subacute prurigo
Authors: Gambichler T , Skrygan M , Werries A , Scola N , Stücker M , Altmeyer P , Kreuter A
Published: June 2010

Background  Subacute prurigo (SP) is a relatively common disease of papular cutaneous lesions that itch intensely. However, there is a lack of systematic clinical and histological studies on SP.

Objectives  We aimed to immunophenotype inflammatory cells in SP using immunohistochemistry and flow cytometry.

Methods  Lesional and non‐lesional skin of 21 patients with SP was investigated. Immunohistochemical staining for CD1a, CD3, CD4, CD8, CD15, CD34, CD68, and anti‐human tryptase (AHT) was performed. In order to evaluate the absolute counts and percentages of CD4+ and CD8+ lymphocytes in the peripheral blood of SP patients, flow cytometric methods were used.

Results  Compared to non‐lesional skin, there was a significant increase of the median percentage of CD3+, CD4+, and CD8+ cells in the lesional dermis (12.6% vs. 19.7%, P = 0.044; 0.8% vs. 3.7%, P = 0.016; and 1% vs. 15.6%, P = 0.0039, respectively). The mean ± SD CD4+/CD8+ ratio was 0.58 ± 0.6. Median percentage of CD15+ cells was significantly increased in lesional skin as compared to non‐lesional skin (11.7 vs. 1%, P = 0.027). Median percentage immunoreactivity of CD68+ cells was significantly increased in lesional dermis as compared to non‐lesional skin (32.5% vs. 9.4%, P = 0.0005). CD1a, CD34, and AHT positive cells did not significantly differ between lesional and non‐lesional skin. T lymphocyte subsets in the peripheral blood of SP patients did not show significant pathologies.

Conclusions  We observed that the inflammatory cell infiltrate in SP mainly consists of T lymphocytes, particularly CD8+ cells, CD15+ neutrophils, and CD68+ macrophages.
Treatment of advanced dermatofibrosarcoma protuberans with imatinib mesylate with or without surgical resection
Authors: Rutkowski P , Dębiec‐Rychter M , Nowecki ZI , Michej W , Symonides M , Ptaszynski K , Ruka W
Published: June 2010

Background Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue sarcoma of the skin characterized by the presence of specific COL1A1–PDGFB fusion protein, which appears as a consequence of the t(17;22) (q22;q13) translocation.

Objective The aim of the study was to perform an analysis of patients with advanced DFSP treated with imatinib, with or without surgery, in clinical practice outside trials.

Patients and Methods We analysed the data of 15 patients (6 male, 9 female; median age 56 years) with locally advanced/initially inoperable and/or metastatic DFSP treated with imatinib 400–800 mg daily between 12/2004 and 06/2009. All diagnoses were ascertained cytogenetically (fluorescent in situ hybridization). Median follow‐up time was 16 months (range: 4–81).

Results Metastases were present in six cases (two lungs, two soft tissue, two lymph nodes). Fibrosarcomatous transformation (FS‐DFSP) was confirmed in seven patients (47%). A 2‐year progression‐free survival (PFS) rate was 60%, and a 2‐year overall survival (OS) rate was 78% (median time for PFS/OS was not reached). The best overall responses were: 10 partial responses (67%, including 5 FS‐DFSP – 1 progressed during the follow‐up), 2 stable diseases (13%) and 3 progressive diseases (20%). Seven patients (47%) underwent resection of residual disease and remained free of disease.

Conclusions We have confirmed the profound anti‐tumour effect of imatinib in DFSP harbouring t(17;22) with long‐term responses. Imatinib therapy may in some cases lead to tumour resectability of lesser disfiguration.
Effect of egg yolk substitution by sweet whey protein isolate on texture, stability and colour of Gelato‐style vanilla ice cream
Authors: ALFAIFI MOSA S , STATHOPOULOS COSTAS E
Published: June 2010

Gelato samples were made with two levels of egg‐yolk (4.5 and 9%). For each level, samples were prepared with and without whey protein isolate (WPI). Texture and melting rates values were significantly (P < 0.05) higher in 9% egg‐yolk samples over the storage period than in samples containing 4.5%. Increasing WPI led to a significant increase in hardness at both levels of egg‐yolk. Gelato with added WPI in 9% samples had slightly higher whiteness (L) and yellowness (b) values than 4.5% samples. A significant effect of fat content was observed in all physical properties measured. Results suggest that this approach can deliver functionality at a lower cost and can produce a good quality Gelato.
Structural changes in endometrial basal glands during menstruation
Authors: Garry R , Hart R , Karthigasu KA , Burke C
Published: June 2010

Please cite this paper as: Garry R, Hart R, Karthigasu KA, Burke C. Structural changes in endometrial basal glands during menstruation. BJOG 2010;117:1175–1185.

Objective  To prospectively observe the changes occurring in endometrial glandular morphology during menstrual shedding and regeneration.

Design  Prospective observational study.

Setting  The academic gynaecological endoscopy unit of a university teaching hospital.

Population  Thirteen patients investigated for a variety of benign, non‐infective gynaecological disorders during the active bleeding phase of the menstrual cycle.

Methods  The morphological appearances of concurrent histological and scanning electron microscopic images of endometrium taken at different stages of the active bleeding phase of menstruation were studied and correlated with the simultaneous immunohistochemical expression of the Ki–67 proliferation marker and the CD68 marker of macrophage activity.

Main outcome measure  Change in morphology of endometrial glands at various stages of menstruation.

Results  Endometrial glands within the basalis show evidence of apoptosis and associated macrophage activity immediately before and during menstruation. There is subsequent destruction and removal of old secretory glandular epithelial elements, and rapid replacement with new narrow glands lined with small epithelial cells. There is no evidence of mitotic cell division or expression of Ki–67 in the glandular cells during this replacement process, but there is evidence of marked macrophage activity prior to glandular cell loss.

Conclusions  Early endometrial epithelial repair after menstruation is not a consequence of mitotic cell division. It occurs without evidence of Ki–67 expression. There is structural evidence of programmed cell death and intense macrophage activity associated with glandular remodelling. Dead epithelial cells are shed from the glands and accumulate within the endometrial cavity to be replaced by new small epithelial cells that appear to arise by differentiation of the surrounding stromal cells. We propose that these stromal cells are endometrial progenitor/stem cells.
Misoprostol dose and route after mifepristone for early medical abortion: a randomised controlled noninferiority trial
Authors: von Hertzen H , Huong NTM , Piaggio G , Bayalag M , Cabezas E , Fang AH , Gemzell‐Danielsson K , Hinh ND , Mittal S , Ng EHY , Chaturachinda K , Pinter B , Puscasiu L , Savardekar L , Shenoy S , Khomassuridge A , Tuyet HTD , Velasco A , Peregoudov A ,   for the WHO Research Group on Postovulatory Methods of Fertility Regulation
Published: June 2010

Please cite this paper as: von Hertzen H, Huong N, Piaggio G, Bayalag M, Cabezas E, Fang A, Gemzell‐Danielsson K, Hinh N, Mittal S, Ng E, Chaturachinda K, Pinter B, Puscasiu L, Savardekar L, Shenoy S, Khomassuridge A, Tuyet H, Velasco A, Peregoudov A, for the WHO Research Group on Postovulatory Methods of Fertility Regulation. Misoprostol dose and route after mifepristone for early medical abortion: a randomised controlled noninferiority trial. BJOG 2010;117:1186–1196.

Objective  To compare 400 and 800 μg sublingual or vaginal misoprostol 24 hours after 200 mg mifepristone for noninferiority regarding efficacy in achieving complete abortion for pregnancy termination up to 63 days of gestation.

Design  Placebo‐controlled, randomised, noninferiority factorial trial, stratified by centre and length of gestation. Misoprostol 400 or 800 μg, administered either sublingually or vaginally, with follow up after 2 and 6 weeks.

Setting  Fifteen obstetrics/gynaecology departments in ten countries.

Population  Pregnant women (n = 3005) up to 63 days of gestation requesting medical abortion.

Methods  Two‐sided 95% CI for differences in failure of complete abortion and continuing pregnancy, with a 3% noninferiority margin, were calculated. Proportions of women with adverse effects were recorded.

Outcome measures  Complete abortion without surgical intervention (main); continuing live pregnancies, induction‐to‐abortion interval, adverse effects, women’s perceptions (secondary).

Results  Efficacy outcomes analysed for 2962 women (98.6%): 90.5% had complete abortion after 400 μg misoprostol, 94.2% after 800 μg. Noninferiority of 400 μg misoprostol was not demonstrated for failure of complete abortion (difference: 3.7%; 95% CI 1.8–5.6%). The 400‐μg dose showed higher risk of incomplete abortion (P < 0.01) and continuing pregnancy (P < 0.01) than 800 μg. Vaginal and sublingual routes had similar risks of failure to achieve complete abortion (P = 0.47, difference in sublingual minus vaginal −0.7%, 95% CI −2.6–1.2%). A similar pattern was observed for continuing pregnancies (P = 0.21). Fewer women reported adverse effects with vaginal than sublingual administration and with the 400‐μg dose than the 800‐μg dose. Of the women, 94% were satisfied or highly satisfied with the regimens, 53% preferred the sublingual route and 47% preferred the vaginal route.

Conclusions  A 400‐μg dose of misoprostol should not replace the 800‐μg dose when administered 24 hours after 200 mg mifepristone for inducing abortion in pregnancies up to 63 days. Sublingual and vaginal misoprostol have similar efficacy, but vaginal administration is associated with a lower frequency of adverse effects.
Management of acute coronary syndromes from a gender perspective
Authors: Alfredsson Joakim , Swahn Eva
Published: June 2010

Acute Coronary Syndromes are the most frequent manifestations of coronary heart disease (CHD). Gender differences in treatment intensity, including differences in level of care, have been reported. Also differences in benefit from certain treatments, especially invasive treatment, have been discussed. Finally, differences in outcome between men and women have been proposed. Results have been inconsistent, partly depending on if and how adjustment for differences in background characteristics has been made.
Acoustic Emissions at High and Low Frequencies During Compression Tests in Brittle Materials
Authors: Schiavi A. , Niccolini G. , Tarizzo P. , Carpinteri A. , Lacidogna G. , Manuello A.
Published: June 2010

Abstract:  The damage process in a concrete specimen subjected to uniaxial compression test is investigated by detection of the propagating elastic waves because of micro‐ and macrocrack growth. Besides the high‐frequency acoustic emissions (AEs), the presence of low‐frequency elastic emissions (ELEs), from 1 to 10 kHz, is detected just before the specimen failure. A spectral analysis of the ELEs is performed by measuring with a calibrated transducer the local acceleration of the specimen surface. Quantitative information about the macrocrack effects in terms of released energy is thus obtained. Furthermore, the evolution of damage is followed through the analysis of the amplitude distribution of AE and ELE signals, distributed according to the Gutenberg–Richter (GR) statistics.
Comparison of Different Techniques for Strain Monitoring of a Biaxially Loaded Cruciform Specimen
Authors: Ramault C. , Makris A. , Van Hemelrijck D. , Lamkanfi E. , Van Paepegem W.
Published: June 2010

Abstract:  This study focuses on the evaluation of several strain measuring techniques for the instrumentation of an in‐plane biaxial test bench. Strain gages, electronic speckle pattern interferometry (ESPI) and digital image correlation (DIC) were used combined or separately to measure the strains in the central gauge area of a biaxially loaded cruciform composite specimen. Applicability of the technique for this specific test and accuracy of the results are important parameters in the evaluation process of the different strain measuring techniques. The results of the three techniques are compared with the results obtained with a 3D finite element (FE) model. It is shown that DIC is the most promising technique because of its full‐field character and ability to cope with vibrations of the test bench. The main drawback remains its incapability to correlate across discontinuities.