bluuebunny/crossref_metadata_2025 huggingface dataset:
New anticoagulants – promising and failed developments
Authors: Harenberg Job , Marx Svetlana , Krejczy Martin , Wehling Martin
Published: July 2011

New direct and indirect acting factor Xa (FXa) and thrombin inhibitors are being developed to overcome the downsides of the conventional anticoagulants – unfractionated and low molecular weight heparins and vitamin K antagonists. Ximelagatran and idraparinux failed to demonstrate an acceptable safety profile. Rivaroxaban and dabigatran are approved for the post‐operative prevention of thromboembolic complications after elective hip or knee replacement surgery; dabigatran is approved for the prevention of embolism in patients with atrial fibrillation in an increasing number of countries. Several novel indirect antithrombin‐dependent anticoagulants as well as antithrombin‐independent oral direct FXa and thrombin inhibitors are investigated in multiple indications for the prophylaxis and treatment of venous thromboembolism and the prophylaxis of arterial thrombotic disorders. Quality‐adjusted life years costs and incremental cost‐effectiveness ratios are relatively high at present, but may decrease after approval of more new anticoagulants for additional indications.
Pentoxifylline aggravates fatty liver in obese and diabetic ob/ob mice by increasing intestinal glucose absorption and activating hepatic lipogenesis
Authors: Massart J , Robin MA , Noury F , Fautrel A , Lettéron P , Bado A , Eliat PA , Fromenty B
Published: July 2011

BACKGROUND AND PURPOSE Pentoxifylline is in clinical trials for non‐alcoholic fatty liver disease and diabetic nephropathy. Metabolic and hepatic effects of pentoxifylline were assessed in a murine model of obesity and type 2 diabetes.

EXPERIMENTAL APPROACH Pentoxifylline (100 mg·kg−1·day−1) was administered for 4 days or 3 weeks in lean and obese/diabetic ob/ob mice. Plasma lipids, glucose, other metabolites and relevant enzymes were measured by standard assays. Hepatic lipids in vivo were assessed with magnetic resonance spectroscopy and by histology. Hepatic extracts were also analysed with RT‐PCR and Western blotting.

KEY RESULTS Four days of pentoxifylline treatment slightly increased liver lipids in ob/ob mice. After 3 weeks, pentoxifylline exacerbated fatty liver and plasma transaminases in ob/ob mice but did not induce liver steatosis in lean mice. Plasma glucose was highest in fed, but not fasted, ob/ob mice treated with pentoxifylline. During the first 10 min of an oral glucose tolerance test, blood glucose increased more rapidly in pentoxifylline‐treated mice. Jejunal expression of glucose transporter 2 isoform was increased in pentoxifylline‐treated obese mice. Hepatic activity of carbohydrate response element binding protein (ChREBP) increased after pentoxifylline in ob/ob, but not lean, mice. Hepatic expression of lipogenic enzymes was highest in pentoxifylline‐treated ob/ob mice. However, pentoxifylline reduced markers of oxidative stress and inflammation in ob/ob liver.

CONCLUSION AND IMPLICATIONS Pentoxifylline exacerbated fatty liver in ob/ob mice through enhanced intestinal glucose absorption, increased postprandial glycaemia and activation of hepatic lipogenesis. Long‐term treatment with pentoxifylline could worsen fatty liver in some patients with pre‐existing hyperglycaemia.
Recombinant viral protein promotes apoptosis and suppresses invasion of ovarian adenocarcinoma cells by targeting α5β1 integrin to down‐regulate Akt and MMP‐2
Authors: Peng Jei‐Ming , Chen Yee‐Hsiung , Hung Shao‐Wen , Chiu Ching‐Feng , Ho Ming‐Yi , Lee Yi‐Jen , Lai Tsung‐Ching , Hsiao Michael , Liang Chi‐Ming , Liang Shu‐Mei
Published: July 2011

BACKGROUND AND PURPOSE As prognosis for patients with metastatic ovarian cancer is generally poor, advances in treatment are needed. Here, we studied the mechanism of action of a recombinant viral capsid protein (rVP1) and explored its effect against ovarian tumour growth and metastasis in vivo.

EXPERIMENTAL APPROACH The human ovarian cancer cell line SKOV3 and BALB/cAnN‐Foxn1 female nude mice were used. Effects of rVP1 on the viability, invasive ability, matrix metalloproteinase (MMP)‐2 activity and cancer cell proliferation and metastasis were determined by cell proliferation assay, Matrigel invasion assay, gelatin zymographic analysis, as well as bioluminescence imaging and immunohistological analysis in xenograft mouse models respectively. Levels of total and phosphorylated focal adhesion kinase (FAK), PKB/Akt, phosphatase and tensin homologue (PTEN) and glycogen synthase kinase‐3β (GSK‐3β) were detected by Western blotting.

KEY RESULTS rVP1 promoted apoptosis and decreased invasion of human ovarian cancer cells. This effect of rVP1 was accompanied by activation of PTEN and GSK‐3β as well as down‐regulation of FAK, Akt and MMP‐2. Anti‐integrin antibodies or overexpression of constitutively active Akt reversed the cellular effects of rVP1. Orthotopic and intraperitoneal xenograft mouse models demonstrated that rVP1 attenuated survival and metastasis of human ovarian cancer SKOV3 cell line in vivo through selective regulation of Akt and GSK‐3β activity as shown by bioluminescence imaging of mice and immunohistochemical analysis.

CONCLUSION AND IMPLICATIONS These results indicate that negative regulation of Akt signalling and MMP‐2 by rVP1 may have the potential to suppress ovarian tumour growth and metastasis in vivo.
The 5‐HT3B subunit affects high‐potency inhibition of 5‐HT3 receptors by morphine
Authors: Baptista‐Hon Daniel T , Deeb Tarek Z , Othman Nidaa A , Sharp Douglas , Hales Tim G
Published: July 2011

BACKGROUND AND PURPOSE Morphine is an antagonist at 5‐HT3A receptors. 5‐HT3 and opioid receptors are expressed in many of the same neuronal pathways where they modulate gut motility, pain and reinforcement. There is increasing interest in the 5‐HT3B subunit, which confers altered pharmacology to 5‐HT3 receptors. We investigated the mechanisms of inhibition by morphine of 5‐HT3 receptors and the influence of the 5‐HT3B subunit.

EXPERIMENTAL APPROACH 5‐HT‐evoked currents were recorded from voltage‐clamped HEK293 cells expressing human 5‐HT3A subunits alone or in combination with 5‐HT3B subunits. The affinity of morphine for the orthosteric site of 5‐HT3A or 5‐HT3AB receptors was assessed using radioligand binding with the antagonist [3H]GR65630.

KEY RESULTS When pre‐applied, morphine potently inhibited 5‐HT‐evoked currents mediated by 5‐HT3A receptors. The 5‐HT3B subunit reduced the potency of morphine fourfold and increased the rates of inhibition and recovery. Inhibition by pre‐applied morphine was insurmountable by 5‐HT, was voltage‐independent and occurred through a site outside the second membrane‐spanning domain. When applied simultaneously with 5‐HT, morphine caused a lower potency, surmountable inhibition of 5‐HT3A and 5‐HT3AB receptors. Morphine also fully displaced [3H]GR65630 from 5‐HT3A and 5‐HT3AB receptors with similar potency.

CONCLUSIONS AND IMPLICATIONS These findings suggest that morphine has two sites of action, a low‐affinity, competitive site and a high‐affinity, non‐competitive site that is not available when the channel is activated. The affinity of morphine for the latter is reduced by the 5‐HT3B subunit. Our results reveal that morphine causes a high‐affinity, insurmountable and subunit‐dependent inhibition of human 5‐HT3 receptors.
All is not fun and games: conversation, play, and surveillance at the Montefeltro court in Urbino
Authors: WEBB JENNIFER D.
Published: July 2011

Works of art and literature commissioned for the Montefeltro court in Urbino and executed by Joos Van Gent, Pedro Berruguete, Baldassare Castiglione and Martino Filetico, use conversation, play, and wit to commemorate humanist interests and court practice. While these and other works celebrate Federico da Montefeltro's court, the illusionism of the intarsia panels in his studiolo do more than amuse. The objects and the uomini illustri portraits that fill the studiolo tease the visitor to the space and point to systems of surveillance and judgment as familiar to the Renaissance courtier as they were to the prisoner in the panopticon.
Intra‐Aortic Balloon Counterpulsation 50 Years Later: Initial Conception and Consequent Ideas
Authors: Moulopoulos Spyridon D.
Published: July 2011

For nearly 50 years, intra‐aortic balloon counterpulsation (IABC) has been the most widely applied temporary assistance method, operating in series with the heart. It helps wean patients from the heart–lung machine after cardiac operations. It is also used in patients with advanced coronary heart disease before and during cardiac and noncardiac operations as well as during percutaneous interventions. Cases of post‐acute myocardial infarction severe cardiogenic shock can also benefit from IABC until or during revascularization or if the latter is impractical. A brief review of mostly experimental attempts is reported as “derivatives” of IABC, as they yielded interesting and sometimes intriguing results that need further investigation.
Acquiring psychomotor skills in operative dentistry: do innate ability and motivation matter?
Authors: Suksudaj N. , Townsend G. C. , Kaidonis J. , Lekkas D. , Winning T. A.
Published: July 2011

Objective:  The acquisition of psychomotor skills is a key competence in the practice of dentistry, and innate abilities and motivation have been shown to influence motor performance. However, the explicit integration of these factors into the design of research projects about skill acquisition in dentistry has been limited. Therefore, the purpose of this study was to provide a comprehensive analysis of how dental students’ abilities and motivation affected their performance in an operative task.

Methods:  A longitudinal study with two cohorts of dental students was conducted in laboratory classes forming part of an operative technique course. A range of standardised psychometric tests was used to assess different abilities before completing a cavity preparation on Frasaco teeth. This was followed immediately by completion of an Intrinsic Motivation Inventory.

Results:  Low but statistically significant correlations (P < 0.05) were found between dental performance and psychomotor ability (r = 0.22), and also dental performance and motivation (r = 0.19). A significant difference (P < 0.05) was found in the grades obtained for the cavity preparation exercise in one cohort between students with higher levels of psychomotor ability compared with those with lower levels (Tracing scores) (P < 0.05). No significant differences in grades obtained for the cavity preparation exercise were found between students with higher and lower levels of motivation.

Conclusion:  Both innate psychomotor ability and motivation showed only weak positive associations with dental performance on cavity preparation exercises. Our study suggests that student‐related factors only provide limited information to explain differences in performance or to be useful as specific predictors of future performance by individuals.
Introduction of a robot patient into dental education
Authors: Tanzawa T. , Futaki K. , Tani C. , Hasegawa T. , Yamamoto M. , Miyazaki T. , Maki K.
Published: July 2011

In recent years, with the increasing social awareness of safety in medical practice, improving clinical skills has become very important, especially for recently graduated dentists. Traditionally, mannequins have been used for clinical skill training, but a mannequin is quite different from a real patient because they have no autonomous movement or conversational ability. This indicates that pre‐clinical simulation education is inadequate. We have, therefore, developed a robot patient that can reproduce an authentic clinical situation for dental clinical training. The robot patient, designed as a full‐body model with a height of 157 cm, has eight degrees of freedom in the head and the ability to perform various autonomous movements. Moreover, saliva secretion and conversation with the trainee can be reproduced. We have introduced the robot patient into an objective structured clinical examination targeted at fifth‐grade students in our dental school to evaluate their skills in cavity preparation, whilst considering the safety of the treatment. As a result, many of the students were able to deal appropriately with a patient’s unexpected movement. Moreover, results of a questionnaire survey showed that almost all the students recognised the educational value of the robot patient especially for ‘risk management’, and they preferred the robot patient to traditional mannequins. Practical application of the robot patient in dental clinical education was evaluated through the experiences of the fifth‐grade students, which showed the effectiveness of the robot patient in the dental field.
The importance of teaching communication in dental education. A survey amongst dentists, students and patients
Authors: Woelber J. P. , Deimling D. , Langenbach D. , Ratka‐Krüger P.
Published: July 2011

The aim of our study was to evaluate the subjective importance of teaching communication in the dental curriculum by conducting a survey amongst dentists, students and patients. Three questionnaires about communication‐related issues were developed in which different questions could be rated on a five‐point Likert scale. These questions included the subjective importance of the dental team’s friendliness, an elaborated consultation, modern office equipment or the dentist’s technical skills. Seven hundred and twenty‐nine questionnaires were completed [233 by dentists (32%), 310 by students (43%) and 185 by patients (25%)]. Eighty‐seven percentage of the dentists, 84% of the students and 84% of the patients supported an integration of communicational issues in dental education; 94.7% of the dentists and 77.2% of the patients attached vital importance to the dentist–patient relationship regarding the therapeutic outcomes. Dentists with prior communicational training experience would spend significantly (P < 0.001) more money for further courses. The results show the publicly perceived importance of integrating aspects of communication in dental education.
The impact of simulated moose densities on conifer aphids along a productivity gradient
Authors: Vesterlund Salla‐Riikka , Suominen Otso , Bergström Roger , Danell Kjell , Persson Inga‐Lill
Published: July 2011

Large herbivores have a significant impact on boreal forest ecosystems. The modification of resources through their feeding induces changes in trophic dynamics and affects the direction of interactions in a community. Moose Alces alces may decrease the available plant biomass for herbivorous insects on one of their main winter forage species in Fennoscandia, Scots pine Pinus sylvestris, and indirectly alter the abundance of invertebrates through exploitative competition. Moose browsing can also induce chemical, morphological, and phenological changes in plants, changing their nutritive value to insect herbivores such as aphids. Habitat productivity may further modify the responses of aphids to moose browsing. We studied the responses of the gray pine aphid Schizolachnus pineti to different moose densities, and their relations to habitat productivity by sampling pine branches and measuring the number of aphids on pine needles. The experimental setup consisted of 8 exclosures along a productivity gradient, where the feeding, defecation, and urination of 4 densities of moose had been simulated for 7 yr. We here show that high levels of simulated browsing decrease the amount of gray pine aphids in areas with high productivity. In areas with low productivity, however, simulated browsing had no such effect. Habitat productivity should therefore be considered as an important factor that may determine the strength of an areas buffering capacity to high moose densities. Low resource environments appear to be favourable to specialist conifer aphids on pines under high browsing pressure, but the performance of generalist insect herbivores might be lowered.
Islands in the sky or squeezed at the top? Ecological causes of elevational range limits in montane salamanders
Authors: Gifford Matthew E. , Kozak Kenneth H.
Published: July 2011

Many animal and plant taxa reach their highest endemism and species richness in montane regions. The study of elevational range limits is central to understanding this widespread pattern and to predicting the responses of montane species to climate change. Yet, because large‐scale manipulations of the distributions of most species are difficult, the causes of species’ elevational range limits (e.g. competitive interactions, physiological specialization) are poorly understood. Here, we harness the power of new mechanistic approaches to dissect the factors that underlie the elevational replacement of two salamander species in the Appalachian Highlands. Our results challenge the long‐held idea that competitive interactions drive the lower elevational range limits of montane species and that physiological stress prevents low‐elevation species from expanding to high elevations. We show that physiological constraints drive the lower elevational range limit of the montane‐endemic species, Plethodon jordani. Conversely, we find that competition with P. jordani prevents the low‐elevation species, P. teyahalee, from expanding its range to include higher‐elevation habitats. These results are broadly consistent with the biogeography and behavior of other montane species, suggesting that similar mechanisms underlie patterns of elevational zonation across a variety of taxa and montane regions. To the extent that our findings are taxonomically and geographically widespread, these results challenge the idea that competitive release at species’ lower elevational range limits is driving the downslope range shifts exhibit by some montane taxa. Instead, our results raise the sobering possibility that even small changes in climate might cause erosion of the ranges of many high‐elevation species.
Common and rare species respond to similar niche processes in macroinvertebrate metacommunities
Authors: Siqueira Tadeu , Bini Luis Mauricio , Roque Fabio Oliveira , Marques Couceiro Sheyla Regina , Trivinho‐Strixino Susana , Cottenie Karl
Published: July 2011

Ecologists have long investigated why communities are composed of a few common species and many rare species. Most studies relate rarity to either niche differentiation among species or spatial processes. There is a parallel between these processes and the processes proposed to explain the structure of metacommunities. Based on a metacommunity perspective and on data on stream macroinvertebrates from different regions of Brazil, we answer two questions. 1) Are sets of common and rare species affected by similar niche and spatial processes? 2) How does the community composition of common and of rare species differ? The main hypothesis we test is that common species are mainly affected by environmental factors, whereas rare species are mostly influenced by dispersal limitation. We used variation partitioning to determine the proportion of variation explained by the environment and space in common and rare species matrices. Contrary to our expectations, evidence supported the idea that both common and rare species are affected mainly by environmental factors, even after controlling for the differing information content between common and rare species matrices. Moreover, the abundance of some common species is also a good predictor of variation in rare species matrices. Niche differences are unlikely to be the sole cause of patterns of rarity in these metacommunities. We suggest that sets of common and rare species react to similar major environmental gradients and that rare species also respond to processes that operate at a more fine‐grained spatial scale, particularly biotic interactions. We extend the view that species sorting is the dominant process structuring metacommunities and argue that future studies focusing on rarity would benefit from a metacommunity perspective.
Fragmentation alters beta‐diversity patterns of habitat specialists within forest metacommunities
Authors: Jamoneau Aurélien , Chabrerie Olivier , Closset‐Kopp Déborah , Decocq Guillaume
Published: July 2011

The relative importance of local, regional and historical factors in controlling the spatial patterns of plant species distribution is still poorly known and challenging for conservation ecology. We conducted an empirical study to link the spatial variation of species and environments among forest patches embedded in contrasted agricultural matrices. We compared how forest herb communities responded to spatial environmental gradients and past forest cover. We found low values of β‐diversity in both unfragmented and highly fragmented systems, independently from local and regional diversities. As fragmentation increased, the spatial structure of local plant communities was more complex and spatial effects explained an increasing proportion of β‐diversity, suggesting that the importance of dispersal limitations increased and played out at broad spatial scales. However, where spatio‐temporal isolation of forest patches was the highest, local species assemblages could not be explained, suggesting that the metacommunity functioning was disrupted. Where the historical continuity was high, local environmental characteristics explained a significant amount of species assemblages within metacommunities, suggesting habitat‐selection processes. Beta‐diversity and variations in presence–absence of species were also influenced by the intensity of landscape management, via the permeability of both forest edges and the matrix. This spatially‐explicit analysis of metacommunities revealed that forest fragmentation impacts beta‐diversity by altering not only the relative importance of deterministic and stochastic processes, but also the spatial scales at which they act. These results provide empirical support for the conservation of ancient forests and the maintenance of a high connectedness between fragments within agricultural landscapes.
Frugivore behaviour determines plant distribution: a spatially‐explicit analysis of a plant‐disperser interaction
Authors: Rodríguez‐Pérez Javier , Wiegand Thorsten , Santamaria Luis
Published: July 2011

The spatial distribution of plants (and other primarily sessile organisms) depends on the interplay between their ecological requirements and the spatial template set before, during, and after the dispersal process. In the case of animal‐dispersed plants, the spatial characteristics of animal behaviour during the seed dispersal process are likely to leave a lasting imprint on plant distribution. Here, we hypothesize that the activity patterns of the frugivorous lizard Podarcis lilfordi directly influence the spatial distribution of the fleshy‐fruited shrub Daphne rodriguezii. To evaluate this hypothesis, we first analysed lizard activity, following radio‐tracked lizards during the plant's fruiting period, and identified its main determinants at several spatial scales of habitat aggregation (from 12.5 to 150 m). We hypothesised that lizard activity depends on differential habitat features explaining its territory use plus habitat preferences associated with each movement bout. In a second step, the most important determinants of lizard activity plus the variables describing habitat structure were used to predict the presence of adult and juvenile plants. Predictability of lizard activity (based on AUC and Pearson regression coefficients) was higher at broad spatial‐scales of habitat aggregation (75 m). The two best predictors of lizard activity were the habitat features of and the distance to the core area (defined as the area enclosing the 0.50 cumulative probability of lizard locations). Plant presence was best predicted by models based on a combination of lizard activity and habitat features at local spatial scales (1.5 m). Best models included habitat features and lizard activity for adult plants, and local‐scale habitat features, the proximity of adult plants and lizard activity for juveniles. In both cases, most plants (50–60%) were located at ‘optimal sites’ (both favourable for lizards and with adequate habitat features), whereas a small fraction of them (3–10%) were located at dispersal‐limited sites (i.e. with adequate habitat features but suboptimal for lizards). Our results thus suggest that the interplay between lizard activity and local habitat features determines the spatial patterns of juvenile‐plant presence and leaves a lasting signature on adult‐plant distribution.
Landscape complexity differentially benefits generalized fourth, over specialized third, trophic level natural enemies
Authors: Rand Tatyana A. , van Veen F. J. Frank , Tscharntke Teja
Published: July 2011

The differential loss of higher trophic levels in the face of natural habitat loss can result in the disruption of important trophic interactions, such as biological control. Natural enemies of herbivorous pests in cropping systems often benefit from the presence of natural habitats in surrounding landscapes, as they provide key resources such as alternative hosts. However, any benefits from a biological control perspective may be dampened if this also enhances enemies at the fourth trophic level. Remarkably, studies of the influence of landscape structure on diversity and interactions of fourth trophic‐level natural enemies are largely lacking. We carried out a large‐scale sampling study to investigate the effects of landscape complexity (i.e. the proportion of non‐crop habitat in the landscapes surrounding focal study areas) on the parasitoid communities of aphids in wheat and on an abundant extra‐field plant, stinging nettle. Primary parasitoid communities (3rd trophic level) attacking the cereal aphid, Sitobion avenae, had little overlap with the communities attacking the nettle aphid, Microlophium carnosum, while secondary parasitoids (4th trophic level) showed high levels of species overlap across these two aphids (25 vs 73% shared species respectively), resulting in significantly higher linkage density and lower specialization for secondary than primary parasitoid webs. In wheat, parasitoid diversity was not related to landscape complexity for either primary or secondary parasitoids. Rates of primary parasitism were generally low, while secondary parasitism rates were high (37–94%) and increased significantly with increasing landscape complexity, although this pattern was driven by a single secondary parasitoid species. Overall, our results demonstrate that extra‐field habitats and landscape complexity can differentially benefit fourth, over third, trophic level natural enemies, and thereby, could dampen biological control. Our results further suggest that fourth trophic‐level enemies may play an important, yet understudied, role in linking insect population dynamics across habitat types.
Analyzing the effects of species gain and loss on ecosystem function using the extended Price equation partition
Authors: Fox Jeremy W. , Kerr Benjamin
Published: July 2011

In nature species richness and composition, as well as the functioning of individual species, all covary along environmental gradients, making it difficult to tease apart their effects on ecosystem function. Here we use a novel extension of the Price equation to partition the causes of functional variation between any two sites sharing at least one species in common. We use the extension to separate effects of species loss from those of species gain; species gain is analogous to migration in evolution. Previous theoretical and empirical studies of biodiversity and ecosystem function fail to distinguish effects of species gain from those of species loss, and so are conceptually incomplete. Application of this approach to data on total plant biomass along an experimental N enrichment gradient leads to novel empirical insights and reveals subtle effects. For instance, effects of species gain are non‐negligible even though enrichment leads to loss of many species and gain of few, and non‐random gain of high‐biomass species reduces the biomass of the persisting species. We also discuss the interpretation of this new approach, which provides a highly‐general partitioning of the factors affecting ecosystem function.
In Vitro Secretion Profile of Pro‐Inflammatory Cytokines IL‐1β, TNF‐α, IL‐6, and of Human Beta‐Defensins (HBD)‐1, HBD‐2, and HBD‐3 from Human Chorioamniotic Membranes After Selective Stimulation with Gardnerella vaginalis
Authors: Zaga‐Clavellina Veronica , Martha Ruiz Velasco‐Muñoz , Flores‐Espinosa Pilar
Published: July 2011

Citation Zaga‐Clavellina V, Martha RV‐M, Flores‐Espinosa P. In vitro secretion profile of pro‐inflammatory cytokines IL‐1β, TNF‐α, IL‐6, and of human beta‐defensins (HBD)‐1, HBD‐2, and HBD‐3 from human chorioamniotic membranes after selective stimulation with Gardnerella vaginalis. Am J Reprod Immunol 2012; 67: 34–43

Problem

Preterm labor associated with infection is a major clinical condition; in this work, we analyze the response of human chorioamniotic membranes stimulated with Gardnerella vaginalis.

Method of study

Using a two‐compartment experimental model, 1 × 106 CFU/mL of G. vaginalis were added to either the amnion or choriodecidua face or to both. Concentrations of IL‐1β, TNF‐α, and IL‐6, as well as human beta defensins (HBD) 1‐3 were quantified by ELISA.

Results

In comparison with control conditions and regardless of the stimulation modality, IL‐1β and IL‐6 increased 4‐fold and 28‐fold, respectively, in the choriodecidual compartment. HBD‐1 increased 2‐fold mainly in the amniotic compartment when the stimulus was applied directly to this region. HBD‐2 and HBD‐3 increased an average of 2‐ and 8‐fold, respectively, in the choriodecidual region.

Conclusions

Stimulation with G. vaginalis induced a tissue‐specific secretion profile of 1L‐1β, IL‐6, and HBD 1‐3 in the chorioamniotic membranes.
The effects of testosterone on craniosynostotic calvarial cells: a test of the gene/environmental model of craniofacial anomalies
Authors: Cray JJ , Durham EL , Smalley MA , Finegold DN , Siegel MI , Losee JE , Mooney MP , Cooper GM
Published: July 2011

To cite this article:
 Cray JJ Jr, Durham EL, Smalley MA, Finegold DN, Siegel MI, Losee JE, Mooney MP, Cooper GM: The effects of testosterone on craniosynostotic calvarial cells: a test of the gene/environmental model of craniofacial anomalies Orthod Craniofac Res 2011;14:149–155

Structured Abstract

Authors –  Cray JJ Jr, Durham EL, Smalley MA, Finegold DN, Siegel MI, Losee JE, Mooney MP, Cooper GM

Introduction –  The gene–environmental interaction model for craniofacial development proposes that if a genetic predisposition for an anomaly is coupled with an environmental factor that can exacerbate this predisposition, more severe phenotypes will result. Here, we utilize cells derived from our non‐syndromic rabbit model of craniosynostosis to test the hypothesis that an insult, testosterone (TP) administration (exogenous source) will alter the osteogenic activity of these cells.

Design –  Calvarial cells from wild‐type (WT) (N = 13) or craniosynostotic (CS) rabbits (N = 11) were stimulated with TP, an androgen receptor blocker, flutamide, and combined treatments. Proliferation and differentiation assays were conducted after 7 days. anova and t‐tests were used to determine differences in stimulation and cell type.

Results –  The CS cells had significantly greater proliferation after TP administration compared to WT. There were no appreciable changes in differentiation after TP stimulation. Flutamide administration or combined TP and flutamide administration decreased both proliferation and differentiation for both cell types similarly.

Conclusions –  Testosterone exposure caused an increase in cell proliferation for CS osteoblast cells. However, a therapy targeted to mitigate this response (flutamide therapy) similarly affected CS and WT cells, suggesting that the administration of flutamide or TP in the presence of flutamide decreases osteogenesis of these cells. Thus, although our data support a mechanism of gene–environmental interaction, these results would not support a therapeutic intervention based on this interaction.
Matrix metalloproteinase proteolysis of the mycobacterial HSP65 protein as a potential source of immunogenic peptides in human tuberculosis
Authors: Shiryaev Sergey A. , Cieplak Piotr , Aleshin Alexander E. , Sun Qing , Zhu Wenhong , Motamedchaboki Khatereh , Sloutsky Alexander , Strongin Alex Y.
Published: July 2011

Mycobacterium tuberculosis is the causative agent of human tuberculosis (TB). Mycobacterial secretory protein ESAT‐6 induces matrix metalloproteinase (MMP)‐9 in epithelial cells neighboring infected macrophages. MMP‐9 then enhances recruitment of uninfected macrophages, which contribute to nascent granuloma maturation and bacterial growth. Disruption of MMP‐9 function attenuates granuloma formation and bacterial growth. The abundant mycobacterial 65 kDa heat shock protein (HSP65) chaperone is the major target for the immune response and a critical component in M. tuberculosis adhesion to macrophages. We hypothesized that HSP65 is susceptible to MMP‐9 proteolysis and that the resulting HSP65 immunogenic peptides affect host adaptive immunity. To identify MMPs that cleave HSP65, we used MMP‐2 and MMP‐9 gelatinases, the simple hemopexin domain MMP‐8, membrane‐associated MMP‐14, MMP‐15, MMP‐16 and MMP‐24, and glycosylphosphatidylinositol‐linked MMP‐17 and MMP‐25. We determined both the relative cleavage efficiency of MMPs against the HSP65 substrate and the peptide sequence of the cleavage sites. Cleavage of the unstructured PAGHG474L C‐terminal region initiates the degradation of HSP65 by MMPs. This initial cleavage destroys the substrate‐binding capacity of the HSP65 chaperone. Multiple additional cleavages of the unfolded HSP65 then follow. MMP‐2, MMP‐8, MMP‐14, MMP‐15 and MMP‐16, in addition to MMP‐9, generate the known highly immunogenic N‐terminal peptide of HSP65. Based on our biochemical data, we now suspect that MMP proteolysis of HSP65 in vivo, including MMP‐9 proteolysis, also results in the abundant generation of the N‐terminal immunogenic peptide and that this peptide, in addition to intact HSP65, contributes to the complex immunomodulatory interplay in the course of TB infection.
The role of the GAF and central domains of the transcriptional activator VnfA in Azotobacter vinelandii
Authors: Yoshimitsu Kyohei , Takatani Nobuyuki , Miura Yukio , Watanabe Yoshihito , Nakajima Hiroshi
Published: July 2011

VnfA is a transcriptional activator that is required for the expression of the structural genes encoding nitrogenase‐2 in Azotobacter vinelandii. VnfA consists of three domains: an N‐terminal regulatory domain termed GAF, including a Cys‐rich motif; a central domain from the AAA+ family; and a C‐terminal domain for DNA binding. Previously, we reported that transcriptionally active VnfA harboring an Fe‐S cluster (presumably of the 3Fe‐4S type) as a prosthetic group and the Cys‐rich motif were possibly associated with coordination of the Fe‐S cluster. In the present study, we have investigated the roles of the GAF and central domains in the regulatory function of VnfA using truncated variants: ΔN15VnfA and ΔGAFVnfA that lack the N‐terminal 15 residues and whole GAF domain, respectively, and GAFVnfA consisting of only the GAF domain. ΔN15VnfA and ΔGAFVnfA lost the ability to bind the Fe‐S cluster, whereas GAFVnfA was still able to bind to the cluster, consistent with the hypothesis that the Cys‐rich motif is essential for Fe‐S cluster binding. The GAF domain showed an inhibitory effect on the transcriptional activity of VnfA, which was reversed in the presence of the Fe‐S cluster, and reactivated upon disassembly of the cluster. The inhibitory activity of the GAF domain acts on the NTPase activity of the central domain, whereas the binding ability of VnfA to DNA was not significantly affected, when VnfA retains its tetrameric conformation. The results imply that a major pathway, by which VnfA function is regulated, operates via the control of NTPase activity by the GAF domain.

Structured digital abstract

 VnfA binds to VnfA by molecular sieving (View Interaction 1, 2)

Database
 VnfA has been submitted to the Swiss‐Prot database under accession number: C1DI41.
A New Approach to Obtaining N α‐t‐Boc‐Amino Acid Aldehydes from Asparagine and Glutamine for Reduced Amide Pseudopeptide Solid‐Phase Synthesis
Authors: Carreño Luisa F. , Alba Martha P. , Varela Yahson , Patarroyo Manuel E. , Lozano José Manuel
Published: July 2011

Reduced amide pseudopeptides have been proposed as structural probes that could be useful as potential malarial vaccine components. However, designing determined pseudopeptide sequences containing isoster peptide bonds, either on an asparagine (Asn) or on a glutamine (Gln) residues, can become difficult because these precursor amino acid aldehydes are obtained in yields lower than 0.5%. This work presents a new strategy for obtaining both Asn and Gln aldehydes based on a controlled side‐chain protection approach as well as a suitable solvent partition procedure. FT‐IR, 1H‐NMR and 13C‐NMR were used for molecule characterization and identification. Amino acid aldehydes were successfully incorporated into a 20‐mer peptide from a malarial‐relevant sequence, and their impact on the molecule’s conformational properties was assessed.
Synthesis and Antileukemic Activity of Novel 4‐(3‐(Piperidin‐4‐yl) Propyl)Piperidine Derivatives
Authors: Vinaya Kambappa , Kavitha Chandagirikoppal V. , Chandrappa Siddappa , Prasanna Doddakunche S. , Raghavan Sathees C. , Rangappa Kanchugarakoppal S.
Published: July 2011

To explore the anticancer effect associated with the piperidine framework, several (substituted phenyl) {4‐[3‐(piperidin‐4‐yl)propyl]piperidin‐1‐yl} methanone derivatives 3(a–i) were synthesized. Variation in the functional group at N‐terminal of the piperidine led to a set of compounds bearing amide moiety. Their chemical structures were confirmed by 1H NMR, IR and mass spectra analysis. Among these, compounds 3a, 3d and 3e were endowed with antiproliferative activity. The most active compound among this series was 3a with nitro and fluoro substitution on the phenyl ring of aryl carboxamide moiety, which inhibited the growth of human leukemia cells (K562 and Reh) at low concentration. Comparison with other derivative (3h) results shown by LDH assay, cell cycle analysis and DNA fragmentation suggested that 3a is more potent to induce apoptosis.
Synthesis of Aryl Aldimines and Their Activity against Fungi of Clinical Interest
Authors: da Silva Cleiton M. , da Silva Danielle L. , Martins Cleide V.B. , de Resende Maria A. , Dias Esther S. , Magalhães Thais F.F. , Rodrigues Letícia P. , Sabino Adão A. , Alves Rosemeire B. , de Fátima Ângelo
Published: July 2011

Aldimines are aldehyde‐derived compounds that contain a C=N group. Besides its broad industrial applications, this class of non‐naturally occurring compounds are found to possess antibacterial, antifungal, antimalarial, antiproliferative, anti‐inflammatory, antiviral, and antipyretic properties. Based on this, six aryl aldimines were synthesized from the condensation of aromatic amines with benzaldehydes. The antifungal activities of synthesized compounds were evaluated against nineteen fungal strains that included Candida and Aspergillus species, Cryptococcus neoformans. The aryl aldimines 2‐(benzylideneamino)phenol (3) and 4‐(benzylideneamino)phenol (8) were the most active compounds against the fungi studied. Compounds 3 and 8 efficiently inhibited the metabolism of C. neoformans mature biofilm.
Design, Synthesis and Structure of Novel Para‐Quinones and their Antibacterial Activity
Authors: Pandurangan Komala , Murnaghan Kevin D. , Walshe Aurora , Müller‐Bunz Helge , Paradisi Francesca , Morgan Grace G.
Published: July 2011

Eight new para‐quinones and one known analogue have been synthesized from p‐chloranil. Five have been structurally characterized by single crystal diffraction, and a range of ligand folding is observed. All nine have been tested for their potency towards Gram(+) S. aureus and Gram(−) E. coli. Quinones 3, 6, 7 and 8 have shown activity towards S. aureus and quinones 3 and 8 also show good activity towards E. coli.
Agency under constraint: Ideological preferences and the politics of electricity regulation in Latin America
Authors: Martinez‐Gallardo Cecilia , Murillo Maria Victoria
Published: July 2011

Whereas both the literature on globalization and the literature on regulatory diffusion stress the pressures that led to policy convergence, this article shows how the ideology of incumbents produced different regulatory outcomes, even in the face of strong financial and technological pressures that constrained policy agency. By looking at the regulatory frameworks adopted at the time of electricity privatization in Latin America, this article shows that right‐wing governments adopted regulations that eliminated barriers to entry and investment and limited the discretion of regulators (market‐conforming regulations), and that former statists who had pragmatically converted to the market creed instead chose regulations that tended to impose higher barriers to entry and investment and gave regulators wide discretion in conflict resolution and price setting (market‐controlling regulations). These findings suggest the need to look at the ideology (and ideological legacies) of government coalitions for a more nuanced understanding of the process of regulatory diffusion that took place across many sectors in most regions of the world.
Naming without shaming: The publication of sanctions in the Dutch financial market
Authors: van Erp Judith
Published: July 2011

Enforcement agencies increasingly disclose or “name and shame” corporate offenders. This article uses responsive regulation as a framework for an empirical study of the impact of non‐anonymous publication of sanctions in the Dutch financial market. These publications are characterized as “naming without shaming”, because they are used for technical guidance rather than with the intention to shame. The findings show that naming offenders functions as a general deterrent in the market for financial intermediaries, but considerably less so in the capital market. In both markets, the publication of sanctions weakened the impact of enforcement. In the capital market, the publications neutralized the seriousness of offenses and contributed to the image of the regulator as powerless. In the market for financial intermediaries, naming offenders was perceived as stigmatizing shaming and led to defiance, rather than compliance. The case study suggests, however, that the publication of sanctions may provide an opportunity for guidance, provided they contain a moral message, rather than technical instruction.
Endoscopic versus microscopic trans‐sphenoidal pituitary surgery: a systematic review and meta‐analysis
Authors: Goudakos J.K. , Markou K.D. , Georgalas C.
Published: July 2011

Clin. Otolaryngol. 2011, 36, 212–220

Background:  Endoscopic trans‐sphenoidal surgery has been increasingly replacing microscopic surgery as the state of the art trans‐sphenoidal approach.

Objective of review:  To assess the efficacy and safety of pure endoscopic approach in comparison with microscopic approach in pituitary surgery.

Type of review:  Literature review and meta‐analysis.

Search strategy:  Systematic literature searches of MEDLINE (1952–10th February 2010), EMBASE (1974–10th February 2010) and the Cochrane Central Register of Controlled Trials to the 10th February 2010.

Evaluation method:  Review of all English‐language studies comparing endoscopic and microscopic techniques.

Results:  Eleven relevant studies were identified with a total of 806 patients, 369 of whom had endoscopic surgery and 437 microscopic surgery. The initial remission rate of hypersecretion of functioning adenomas was not significantly different between the endoscopic and the microscopic group [(OR: 1.34(95% CI: 0.73–2.47); P = 0.35; 66% remission rate in endoscopic group versus 60% in microscopic)].The proportion of patients with complete tumour removal was not significantly different in the endoscopic group than in the microscopic group [(OR: 0.83, (95% CI: 0.52–1.33); P = 0.44]. The rate of CSF leak attributable to the surgical method did not differ significantly between endoscopic and microscopic group. Post‐operative diabetes insipidus was less frequent in those having endoscopic surgery [15%versus 28%P = 0.003]. Regarding the other intra cranial and nasal complications attributable to surgical technique, the occurrence rate in endoscopic group was significant lower compared with microscopic group (13%versus 1.2% respectively, P < 0.05). Patients in the endoscopic group had significant shorter postoperative hospital stay with a range from 3.7 to 4.4 days, than those of microscopic group with a range from 5.4 to 5.7 days [(WMD: −1.53, (95% CI: −2.30 to −0.77); P < 0.00001)].

Conclusions:  Notwithstanding its limitations, the present systematic review, based on the currently available evidence, suggests that endoscopic trans‐sphenoidal pituitary surgery is associated with similar rates of complete tumour excision and remission rates. Endoscopic surgery was associated with fewer complications related to surgical technique and a shorter hospital stay.
Management of patients receiving oral anticoagulants using computer dosing software – does everyone agree? Data from a UK NEQAS (blood coagulation) exercise
Authors: JENNINGS I. , WALKER I. D. , KITCHEN S. , KITCHEN D. , WOODS T. A. L. , KEELING D. , WARNER B. , COTTON P. , MacLEAN R.
Published: July 2011

Introduction:  The quality of anticoagulation management is not readily or frequently assessed, particularly between different centres. This study sought to evaluate agreement in oral anticoagulant management decisions between participating centres in UK NEQAS programmes.

Methods:  Participants were asked to indicate whether they used computerized dosing support software (CDSS) and to complete a series of questions with respect to anticoagulant management provision. Four clinical scenarios were provided, together with past and current International Normalised Ratio (INR) results. Participants were asked to provide recommendations on the target INR they would assign to the patient, the dose of warfarin and a recall interval.

Results:  Seven hundred and fifty‐nine centres returned results, of which 28% were enrolled in the hospital‐based EQA programme, and 72% were participants in the point‐of‐care testing programme. Six hundred (79%) reported use of CDSS. In one straightforward scenario, there was 99% agreement in dose recommendation. However, for three more complex scenarios, differences were apparent in target INRs employed and both dose and recall recommendations. In some cases, differences related to the software system employed.

Conclusion:  The study emphasizes large variation in the approach to managing these scenarios and warrants further investigation, together with education including promoting national guidelines for the assignment of target ranges.