bluuebunny/crossref_metadata_2025 huggingface dataset:
Arp2/3 complex–dependent actin networks constrain myosin II function in driving retrograde actin flow
Authors: Yang Qing , Zhang Xiao-Feng , Pollard Thomas D. , Forscher Paul
Published: June 2012

The Arp2/3 complex nucleates actin filaments to generate networks at the leading edge of motile cells. Nonmuscle myosin II produces contractile forces involved in driving actin network translocation. We inhibited the Arp2/3 complex and/or myosin II with small molecules to investigate their respective functions in neuronal growth cone actin dynamics. Inhibition of the Arp2/3 complex with CK666 reduced barbed end actin assembly site density at the leading edge, disrupted actin veils, and resulted in veil retraction. Strikingly, retrograde actin flow rates increased with Arp2/3 complex inhibition; however, when myosin II activity was blocked, Arp2/3 complex inhibition now resulted in slowing of retrograde actin flow and veils no longer retracted. Retrograde flow rate increases induced by Arp2/3 complex inhibition were independent of Rho kinase activity. These results provide evidence that, although the Arp2/3 complex and myosin II are spatially segregated, actin networks assembled by the Arp2/3 complex can restrict myosin II–dependent contractility with consequent effects on growth cone motility.
Lis1 is an initiation factor for dynein-driven organelle transport
Authors: Egan Martin J. , Tan Kaeling , Reck-Peterson Samara L.
Published: June 2012

The molecular motor cytoplasmic dynein is responsible for most minus-end–directed, microtubule-based transport in eukaryotic cells. It is especially important in neurons, where defects in microtubule-based motility have been linked to neurological diseases. For example, lissencephaly is caused by mutations in the dynein-associated protein Lis1. In this paper, using the long, highly polarized hyphae of the filamentous fungus Aspergillus nidulans, we show that three morphologically and functionally distinct dynein cargos showed transport defects in the genetic absence of Lis1/nudF, raising the possibility that Lis1 is ubiquitously used for dynein-based transport. Surprisingly, both dynein and its cargo moved at normal speeds in the absence of Lis1 but with reduced frequency. Moreover, Lis1, unlike dynein and dynactin, was absent from moving dynein cargos, further suggesting that Lis1 is not required for dynein-based cargo motility once it has commenced. Based on these observations, we propose that Lis1 has a general role in initiating dynein-driven motility.
Meiotic cohesin complexes are essential for the formation of the axial element in mice
Authors: Llano Elena , Herrán Yurema , García-Tuñón Ignacio , Gutiérrez-Caballero Cristina , de Álava Enrique , Barbero José Luis , Schimenti John , de Rooij Dirk G. , Sánchez-Martín Manuel , Pendás Alberto M.
Published: June 2012

Cohesin is a conserved multisubunit protein complex that participates in chromosome segregation, DNA damage repair, chromatin regulation, and synaptonemal complex (SC) formation. Yeast, but not mice, depleted of the cohesin subunit Rec8 are defective in the formation of the axial elements (AEs) of the SC, suggesting that, in mammals, this function is not conserved. In this paper, we show that spermatocytes from mice lacking the two meiosis-specific cohesin subunits RAD21L and REC8 were unable to initiate RAD51- but not DMC1-mediated double-strand break repair, were not able to assemble their AEs, and arrested as early as the leptotene stage of prophase I, demonstrating that cohesin plays an essential role in AE assembly that is conserved from yeast to mammals.
Some properties of coupled-expanding maps in compact sets
Authors: Zhang Xu , Shi Yuming , Chen Guanrong
Published: June 2012

In this paper, some properties of a strictly

A
A

-coupled-expanding map in compact subsets of a metric space are studied, where

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A

is a transition matrix. It is shown that this map has a compact invariant set on which it is topologically semi-conjugate to the subshift for

A
A

. If the subshift for

A
A

has positive topological entropy, then the map is chaotic in the sense of Li-Yorke. Moreover, in the one-dimensional case, the map is at most two-to-one conjugate to the subshift for

A
A

and chaotic in the sense of Devaney.
fus/TLS orchestrates splicing of developmental regulators during gastrulation
Authors: Dichmann Darwin S. , Harland Richard M.
Published: June 2012

Here we investigated the function of the atypical RNA-binding protein fus/TLS (fused in sarcoma/translocated in sarcoma) during early frog development. We found that fus is necessary for proper mRNA splicing of a set of developmental regulatory genes during early frog development and gastrulation. Upon fus knockdown, embryos fail to gastrulate and show mesodermal differentiation defects that we connect to intron retention in fgf8 (fibroblast growth factor 8) and fgfr2 (fgf receptor 2) transcripts. During gastrulation, the animal and marginal regions dissociate, and we show that this is caused, at least in part, by intron retention in cdh1 transcripts. We confirm the specificity of splicing defects at a genomic level using analysis of RNA sequencing (RNA-seq) and show that 3%–5% of all transcripts display intron retention throughout the pre-mRNA. By analyzing gene ontology slim annotations, we show that the affected genes are enriched for developmental regulators and therefore represent a biologically coherent set of targets for fus regulation in embryogenesis. This shows that fus is central to embryogenesis and may provide information on its function in neurodegenerative disease.
Accurate assessment of cell density in low cellular liquid‐based cervical cytology
Authors: Siebers A. G. , van der Laak J. A. W. M. , Huberts‐Manders R. , Vedder J. E. M. , Bulten J.
Published: June 2012

A. G. Siebers, J. A. W. M. van der Laak, R. Huberts‐Manders, J. E. M. Vedder and J. Bulten

Accurate assessment of cell density in low cellular liquid‐based cervical cytology

Objective:  Scant cellularity is the most important source of unsatisfactory liquid‐based cytology. Although still being debated, low cellularity is thought to compromise the detection of squamous lesions. Thus, reliable assessment of cellularity is essential. The aim of the present study was to determine the cellularity range for ThinPrep® slides of low cellularity and to establish the most accurate cell‐counting protocol.

Methods:  A series of 60 ThinPrep cases representing the full spectrum of adequate, ‘satisfactory but limited by’ (SBLB) and unsatisfactory reports were included. Two cell‐counting protocols with three different magnifications, using ×10, ×20 and ×40 objectives, were evaluated and related to the true cellularity, together with a reassessment of the degree of adequacy originally reported. The cell‐counting protocol that showed the highest correlation coefficient was considered the most accurate.

Results:  Based on seven (re)assessments a majority score for adequacy was established. There were 42 cases with a majority score ‘unsatisfactory’ or ‘SBLB’ (low cellularity) of which 41 contained fewer than 20 000 squamous cells; and 18 cases with a majority score ‘satisfactory’ of which one had fewer than 20 000 cells. The cell‐counting protocol that showed the significantly highest correlation with the reference standard was the Stichting Kwaliteitsbewaking Medische Laboratoriumdiagnostiek (SKML) protocol with a ×10 objective.

Conclusions:  ThinPrep slides reported as unsatisfactory or SBLB were shown to contain fewer than 20 000 squamous cells. The most accurate protocol for estimating the cellularity of these slides was cell counting in five non‐adjacent microscope fields along the horizontal axis and five along the vertical axis of the slide with a ×10 objective and applying a correction factor of 1.24× to correct for underestimation of the true cellularity.
Foraging rules of flower selection applied by colonies of Apis mellifera: ranking and associations of floral sources
Authors: Aronne Giovanna , Giovanetti Manuela , Guarracino Mario R. , de Micco Veronica
Published: June 2012

1. Interactions between bees and flowers are historically a key topic of research in biology. Apis mellifera is known to forage on a wide variety of flowers to collect nectar and/or pollen. Until now, resource collection strategies were investigated focusing on the influence of single factors on foraging decisions, such as hive requirements, surrounding vegetation, resource availability, seasonality and interactions with other bees. Despite the vast amount of literature on A. mellifera, we lack a comprehensive view of its flower selection.

2. Our aim was to go beyond specific circumstances in order to identify general criteria for flower selection at species level. Applying data mining techniques (Market Basket Analysis), we found that bees exert a precise flower selection choice mainly driven by their pollen requirements. The bees foraged all over the study area with no obvious preference for the close surrounding vegetation. They selected a restricted number of all the available sources, for nectar as well as for pollen. Apis mellifera chose some floral sources more regularly than others. The most recurrent sources changed in time according to subsequent flowering peaks and often corresponded to anemophilous species. The compelling need for pollen revealed the constant demand of a few distinct floral sources. Plants providing huge quantities of pollen, such as wind‐pollinated species, were preferred. When the pollen source also provided a good quantity of nectar, foragers collected both resources on the same species.

3. This work on A. mellifera helps to clarify some of the complex aspects of its floral selection processes, which emerge from studies on single colonies, areas or environmental factors influencing individual foraging behaviours. It also suggests that some established theories on pollinator–flower interactions, such as the role of wind‐pollinated species, need revision.
Imbalance of MMP‐2 and MMP‐9 expression versus TIMP‐1 and TIMP‐2 reflects increased invasiveness of human testicular germ cell tumours
Authors: Milia‐Argeiti E. , Huet E. , Labropoulou V. T. , Mourah S. , Fenichel P. , Karamanos N. K. , Menashi S. , Theocharis A. D.
Published: June 2012

The histological classification of testicular germ cell tumours (TGCTs) to seminoma or non‐seminomatous germ cell tumours is at present the main criterion for the clinical outcome and selection of the treatment strategy. In view of the need to identify novel prognostic biomarkers for TGCTs, we investigated the expression of the matrix metalloproteinases MMP‐2 and MMP‐9 in testicular tumour tissues and cell lines of both seminoma and non‐seminoma origin. Immunohistochemistry and zymography analysis of tumoural tissues showed significantly higher levels of MMP‐2 and MMP‐9 compared with normal testis with the active forms detected only in the tumour tissues. Three cell lines representative of the different tumour types, JKT‐1 seminoma, NCCIT teratocarcinoma and NTERA2/D1 embryonal carcinoma were also evaluated for their expression of these MMPs using qPCR and zymography and for their invasive properties. The more invasive non‐seminomatous teratocarcinoma and embryonal cells expressed considerably more MMP‐2 and MMP‐9 compared with seminoma cells exhibiting lower invasiveness. Furthermore, an inverse relation was observed between invasiveness and the expression of endogenous inhibitors TIMP‐1 and TIMP‐2. The MMP inhibitor Marimastat inhibited invasion in all cell lines, the highest inhibition was observed in the more invasive NTERA2/D1 and NCCIT cells, which presented the highest ratio of MMP‐2 and MMP‐9 vs. TIMP‐1 and TIMP‐2. These results highlight the importance of MMP‐2 and MMP‐9 in the invasiveness of testicular tumours and suggest that their levels, vs. those of TIMP‐1 and TIMP‐2, may represent potential biomarkers for testicular malignancy.
Effects of nucleotides adenosine monophosphate and adenosine triphosphate in combination with L‐arginine on male rabbit corpus cavernosum tissue
Authors: Hupertan V. , Neuzillet Y. , Stücker O. , Pons C. , Leammel E. , Lebret T.
Published: June 2012

Purines and more specifically adenosine monophosphate (AMP) and adenosine triphosphate (ATP) have a strong relaxant effect on smooth muscle cells of the dog, rabbit and human corpus cavernosum, to approximately the same degree as nitric oxide (NO). However, purines are considered as modulators of erectile function rather than key mediators. This suggests that the use of purines combined with NO donors could be effective to treat some specific erectile disorders. The relaxation induced by the combination of l‐arginine (Arg), a natural substrate for NO synthase, was assessed with a purine‐nucleotide (AMP, ATP) on a rabbit corpus cavernosum model, to determine if these substances could potentiate each other’s effect. When a pre‐contraction was induced by phenylephrine, AMP alone induced a 43% CC relaxation rate and ATP alone a 26% rate. The relaxation rate induced by Arg was lower in comparison (8% at 5.10−4 m vs. 25% at AMP 5.10−4 m and 15% at ATP 5.10−4 m). NO synthase inhibitor n‐nitro‐l‐arginine did not modify the relaxing effect provoked by AMP suggesting that the mechanism of action of this nucleotide does not involve the NO pathway. The combination of Arg at 5.10−4 m with either AMP or ATP at different doses ranging from 5.10−4 to 10−3 m significantly enhanced the relaxing response reaching rates of 62 and 80% respectively, leading to a synergistic effect. The present data indicate that a ‘NO donor’ combined with an ‘adenosine donor’ could be an effective therapeutic approach.
Landscape structure and land use history influence changes in island plant composition after 100 years
Authors: Aggemyr Elsa , Cousins Sara A. O.
Published: June 2012

Aim We investigated how current and historical land use and landscape structure affect species richness and the processes of extinction, immigration and species turnover.

Location The northern part of the Stockholm archipelago, Baltic Sea, Sweden. We resurveyed 27 islands ranging from 0.3 to 33 ha in area.

Methods We compared current plant survey data, cadastral maps and aerial photographs with records obtained from a survey in 1908, using databases and a digital elevation model to examine changes in plant community dynamics in space and time. We examined the effects of local and landscape structure and land use changes on plant species dynamics by using stepwise regression in relation to eight local and three landscape variables. The eight local variables were area, relative age, shape, soil heterogeneity, bedrock ratio, number of houses, forest cover change, and grazing 100 years ago. The three landscape variables were distance to mainland, distance to closest island with a farm 100 years ago, and structural connectivity. Hanski’s connectivity measure was modified to incorporate both connectivity and fragmentation.

Results The investigated islands have undergone drastic changes, with increasing forest cover, habitation, and abandonment of grassland management. Although the total species richness increased by 31% and mean island area by 23%, we found no significant increase in species richness per unit area. Local variables explain past species richness (100 years ago), whereas both local and landscape variables explain current species richness, extinctions, immigrations and species turnover. Grazing that occurred 100 years ago still influences species richness, even though grazing management was abandoned several decades ago. The evidence clearly shows an increase in nitrophilous plant species, particularly among immigrant species.

Main conclusions This study highlights the importance of including land use history when interpreting current patterns of species richness. Furthermore, local environment and landscape patterns affect important ecological processes such as immigration, extinction and species turnover, and hence should be included when assessing the impact of habitat fragmentation and land use change. We suggest that our modified structural connectivity measure can be applied to other types of landscapes to investigate the effects of fragmentation and habitat loss.
Chronic Disease Management Programmes: an adequate response to patients’ needs?
Authors: Rijken Mieke , Bekkema Nienke , Boeckxstaens Pauline , Schellevis François G. , De Maeseneer Jan M. , Groenewegen Peter P.
Published: June 2012

Background  Inspired by American examples, several European countries are now developing disease management programmes (DMPs) to improve the quality of care for patients with chronic diseases. Recently, questions have been raised whether the disease management approach is appropriate to respond to patient‐defined needs.

Objective  In this article we consider the responsiveness of current European DMPs to patients’ needs defined in terms of multimorbidity, functional and participation problems, and self‐management.

Method  Information about existing DMPs was derived from a survey among country‐experts. In addition, we made use of international scientific literature.

Results  Most European DMPs do not have a solid answer yet to the problem of multimorbidity. Methods of linking DMPs, building extra modules to deal with the most prevalent comorbidities and integration of case management principles are introduced. Rehabilitation, psychosocial and reintegration support are not included in all DMPs, and the involvement of the social environment of the patient is uncommon. Interventions tailored to the needs of specific social or cultural patient groups are mostly not available. Few DMPs provide access to individualized patient information to strengthen self‐management, including active engagement in decision making.

Conclusion  To further improve the responsiveness of DMPs to patients’ needs, we suggest to monitor ‘patient relevant outcomes’ that might be based on the ICF‐model. To address the needs of patients with multimorbidity, we propose a generic comprehensive model, embedded in primary care. A goal‐oriented approach provides the opportunity to prioritize goals that really matter to patients.
Identification of Quantitative Trait Loci for Bacterial Blight Resistance Derived from Oryza meyeriana and Agronomic Traits in Recombinant Inbred Lines of Oryza sativa
Authors: Chen Li‐Na , Yang Yong , Yan Cheng‐Qi , Wang Xu‐Ming , Yu Chu‐Lang , Zhou Jie , Zhang Wei‐Lin , Cheng Ye , Cheng Xiao‐Yue , Chen Jian‐Ping
Published: June 2012

Bacterial blight (BB) is one of the major diseases that affect rice productivity. In previous studies, BB resistance was transferred to cultivated rice Oryza sativa from wild rice Oryza meyeriana using asymmetric somatic hybridization. One of the resistant hybrid progenies (Y73) has also been shown to possess novel resistance gene(s) different from any of those previously associated with BB resistance. We have mapped quantitative trait loci (QTLs) for BB resistance in a recombinant inbred line (RIL) population derived from a cross between Y73 and a BB‐susceptible cv. IR24. Five QTLs were detected where Y73 alleles contributed to increased BB resistance. Three minor QTLs were identified on chromosomes 3, 10 and 11, and two major QTLs on chromosomes 1 and 5, respectively. QTL on chromosome 5, designated qBBR5, had the strongest effect on BB resistance, explaining approximately 37% of the phenotypic variance. Using the same RIL population, we also mapped QTLs for agronomic traits including plant height (PH), heading date (HD), plant yield (PYD) and PYD component traits. A total of 21 QTLs were identified, of which four were detected for PH, six for HD, three for panicle number per plant (PNPP), one for spikelets per panicle (SPP), six for 1000‐grain weight (TGW) and one for PYD. qPH1 (a QTL for PH) was found in the same interval as qBBR1 for BB resistance, and qHD11 for HD and qBBR11 for BB resistance also shared a similar interval. Additionally, BB resistance was significantly correlated with PH or HD in the RIL population. This suggests that the resistance genes may have pleiotropic effects on, or close linkage to, genes controlling PH or HD. These results will help deduce the resistance mechanisms of the novel resistance gene(s) and provide the basis for cloning them and using them in marker‐assisted breeding.
Preventive effect of danshensu on selenite‐induced cataractogenesis in cultured rat lens
Authors: Qi Hui‐Ping , Wei Shu‐Qin , Zhang Li‐Qiong , Gao Xiang‐Chun , Yu Nan‐Nan , Bi Sheng , Cui Hao
Published: June 2012

Abstract

Background:  To investigate the preventive effect of danshensu on the selenite‐induced opacification of cultured rat lenses.

Methods:  Isolated lens were divided into three groups with eight lenses in each group. Group I: lenses were incubated with M199 medium alone; Group II: incubated in M199 containing 200 µmol/L sodium selenite; Group III: incubated in M199 containing 200 µmol/L sodium selenite and 500 µmol/L danshensu. Selenite was administered on the third day, and danshensu treatment was from the second to the fifth day. Cataracts development was observed using an inverted microscope, and the lenses were analysed for total anti‐oxidative capabilities, mean activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S‐transferase; levels of reduced glutathione; malondialdehyde; and total sulfhydryl content.

Results:  All lenses in Group I were clear, whereas all lenses in Group II developed dense vacuolization and opacification. In Group III, 25% lenses revealed minimal vacuolization, and 75% showed no opacification or vacuolization. Total anti‐oxidative capabilities and the mean activities of anti‐oxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S‐transferase; levels of glutathione; and total sulfhydryl content were elevated, and the level of malondialdehyde was decreased following treatment with danshensu compared with Group II.

Conlusion:  The anti‐oxidative properties of danshensu may play a major role in its contribution to the anticataract effect.
Engrailed signaling in axon guidance and neuron survival
Authors: Fuchs Julia , Stettler Olivier , Alvarez‐Fischer Daniel , Prochiantz Alain , Moya Kenneth L. , Joshi Rajiv L.
Published: June 2012

Several homeoproteins can function in a direct cell non‐autonomous fashion to control various biological processes. In the developing nervous system, this mode of signaling has been well documented for Engrailed in the guidance of retinal ganglion cell axons and retino‐tectal patterning. Engrailed is also a key factor for mesencephalic dopaminergic (mDA) neurons, not only during development but also in the adult. Haplodeficiency for Engrailed1 leads to progressive adult‐onset loss of mDA neurons and several phenotypic alterations reminiscent of Parkinson’s disease (PD). Thanks to its transduction properties, Engrailed has been shown to confer neuroprotection in several experimental models of PD. Study of the mechanisms underlying these two Engrailed‐mediated effects has revealed a key role of the translation regulation by Engrailed and uncovered an unsuspected link between a homeoprotein and mitochondrial activity. These studies highlight the crucial role of cellular energetic metabolism in neuron development, survival and neurodegeneration, and may help to identify novel therapeutic targets.
Timing of developmental sequences in different brain structures: physiological and pathological implications
Authors: Dehorter N. , Vinay L. , Hammond C. , Ben‐Ari Y.
Published: June 2012

The developing brain is not a small adult brain. Voltage‐ and transmitter‐gated currents, like network‐driven patterns, follow a developmental sequence. Studies initially performed in cortical structures and subsequently in subcortical structures have unravelled a developmental sequence of events in which intrinsic voltage‐gated calcium currents are followed by nonsynaptic calcium plateaux and synapse‐driven giant depolarising potentials, orchestrated by depolarizing actions of GABA and long‐lasting NMDA receptor‐mediated currents. The function of these early patterns is to enable heterogeneous neurons to fire and wire together rather than to code specific modalities. However, at some stage, behaviourally relevant activities must replace these immature patterns, implying the presence of programmed stop signals. Here, we show that the developing striatum follows a developmental sequence in which immature patterns are silenced precisely when the pup starts locomotion. This is mediated by a loss of the long‐lasting NMDA‐NR2C/D receptor‐mediated current and the expression of a voltage‐gated K+ current. At the same time, the descending inputs to the spinal cord become fully functional, accompanying a GABA/glycine polarity shift and ending the expression of developmental patterns. Therefore, although the timetable of development differs in different brain structures, the g sequence is quite similar, relying first on nonsynaptic events and then on synaptic oscillations that entrain large neuronal populations. In keeping with the ‘neuroarcheology’ theory, genetic mutations or environmental insults that perturb these developmental sequences constitute early signatures of developmental disorders. Birth dating developmental disorders thus provides important indicators of the event that triggers the pathological cascade leading ultimately to disease.
AMPA receptors as drug targets in neurological disease – advantages, caveats, and future outlook
Authors: Chang Philip K.‐Y. , Verbich David , McKinney R. Anne
Published: June 2012

Most excitatory transmission in the brain is mediated by the AMPA receptor subtype of the ionotropic glutamate receptors. In many neurological diseases, synapse structure and AMPA receptor function are altered, thus making AMPA receptors potential therapeutic targets for clinical intervention. The work summarized in this review suggests a link between AMPA receptor function and debilitating neuropathologies, and discusses the current state of therapies targeting AMPA receptors in four diseases. In amyotrophic lateral sclerosis, AMPA receptors allow cytotoxic levels of calcium into neurons, leading to motor neuron death. Likewise, in some epilepsies, overactivation of AMPA receptors leads to neuron damage. The same is true for ischemia, where oxygen deprivation leads to excitotoxicity. Conversely, Alzheimer’s disease is characterized by decreased AMPA activation and synapse loss. Unfortunately, many clinical studies have had limited success by directly targeting AMPA receptors in these diseases. We also discuss how the use of AMPA receptor modulators, commonly known as ampakines, in neurological diseases initially seemed promising in animal studies, but mostly ineffective in clinical trials. We propose that indirectly affecting AMPA receptors, such as by modulating transmembrane AMPA receptor regulatory proteins or, more generally, by regulating glutamatergic transmission, may provide new therapeutic potential for neurological disorders.
Cra regulates the cross‐talk between the two branches of the phosphoenolpyruvate : phosphotransferase system of Pseudomonas putida
Authors: Chavarría Max , Fuhrer Tobias , Sauer Uwe , Pflüger‐Grau Katharina , de Lorenzo Víctor
Published: June 2012

The gene that encodes the catabolite repressor/activator, Cra (FruR), of Pseudomonas putida is divergent from the fruBKA operon for the uptake of fructose via the phosphoenolpyruvate : carbohydrate phosphotransferase system (PTSFru). The expression of the fru cluster has been studied in cells growing on substrates that change the intracellular concentrations of fructose‐1‐P (F1P), the principal metabolic intermediate that counteracts the DNA‐binding ability of Cra on an upstream operator. While the levels of the regulator were not affected by any of the growth conditions tested, the transcription of fruB was stimulated by fructose but not by the gluconeogenic substrate, succinate. The analysis of the PfruB promoter activity in a strain lacking the Cra protein and the determination of key metabolites revealed that this regulator represses the expression of PTSFru in a fashion that is dependent on the endogenous concentrations of F1P. Because FruB (i.e. the EI‐HPr‐EIIAFru polyprotein) can deliver a high‐energy phosphate to the EIIANtr (PtsN) enzyme of the PTSNtr branch, the cross‐talk between the two phosphotransferase systems was examined under metabolic regimes that allowed for the high or low transcription of the fruBKA operon. While fructose caused cross‐talk, succinate prevented it almost completely. Furthermore, PtsN phosphorylation by FruB occurred in a Δcra mutant regardless of growth conditions. These results traced the occurrence of the cross‐talk to intracellular pools of Cra effectors, in particular F1P. The Cra/F1P duo seems to not only control the expression of the PTSFru but also checks the activity of the PTSNtrin vivo.
Advances in molecular systematics of the vetigastropod superfamily Trochoidea
Authors: Williams Suzanne T.
Published: June 2012

Williams, S.T. (2012). Advances in molecular systematics of the vetigastropod superfamily Trochoidea. —Zoologica Scripta, 41, 571–595.

The gastropod superfamily Trochoidea Rafinesque, 1815 is comprised of a diverse range of species, including large and charismatic species of commercial value as well as many small or enigmatic taxa that are only recently being represented in molecular studies. This study includes the first sequences for rarely collected species from the genera Gaza Watson, 1879, Callogaza Dall, 1881, Antimargarita Powell, 1951 and Kaiparathina Laws, 1941. There is also greater taxon sampling of genera that have proved difficult to place in previous phylogenetic analyses, like Tectus Montfort, 1810, Tegula Lesson, 1832, Margarites Gray, 1847, Margarella Thiele, 1893 and trochoid skeneimorphs. There is also greater sampling of poorly represented families Solariellidae and Liotiidae. Bayesian analysis of combined gene data sets based on four (28S, 12S, 16S and COI) or five genes (plus 18S) suggests that there are eight, possibly nine families in Trochoidea including the families Margaritidae and Tegulidae, which are recognized for the first time at familial rank. Other trochoidean families confirmed are Calliostomatidae, Liotiidae, Skeneidae, Solariellidae, Trochidae and Turbinidae. A clade including Cittarium and the commercially important genera Rochia and Tectus may represent a possible ninth family, but this is not formally recognized or described here and awaits confirmation from further studies. Relationships among families were not generally well supported except in the 5‐gene tree. In the 5‐gene tree, Turbinidae, Liotiidae, Tegulidae, Cittarium, Rochia and Tectus form a well‐supported clade consistent with the previous molecular and morphological studies linking these groups. This clade forms another well‐supported clade with Margaritidae and Solariellidae. Trochidae is sister to Calliostomatidae with strong support. Subfamilial relationships within Trochidae are consistent with recent molecular studies, with the addition of one new subfamily, Kaiparathininae Marshall 1993 (previously a tribe). Only two subfamilies are recognized within Turbinidae, both with calcareous opercula: Prisogasterinae and Turbininae. Calliostomatidae includes a new subfamily Margarellinae. Its assignment to Calliostomatidae, although well supported by molecular evidence, is surprising considering morphological evidence.
Costs of diabetes; new figures for Type 1 and Type 2 diabetes
Authors: Hitman G. A.
Published: June 2012

Diabet. Med. 29, 835 (2012)
The malignant obesity hypoventilation syndrome (MOHS)
Authors: Marik P. E.
Published: June 2012

We have coined the term ‘malignant obesity hypoventilation syndrome’ (MOHS) to describe a severe multisystem disease due to the systemic effects of obesity. Patients with this syndrome have severe obesity‐related hypoventilation together with systemic hypertension, diabetes and the metabolic syndrome, left ventricular hypertrophy with diastolic dysfunction, pulmonary hypertension and hepatic dysfunction. This syndrome is largely unrecognized as physicians do not make the association between the patients' multiple medical problems and obesity. Because of the delayed diagnosis and progressive morbidities of this condition, all patients with a body mass index of more than 40 kg m−2 should be screened for MOHS. The management of patients with MOHS includes short‐term measures to improve the patients' medical condition and long‐term measures to achieve enduring weight loss. Bariatric surgery reverses or improves the multiple metabolic and organ dysfunctions associated with MOHS and should be strongly considered in these patients.
How much do M&M's weigh?
Authors: Froelich Amy G. , Stephenson W. Robert
Published: June 2012

This article presents activities appropriate for the first half of a general introductory statistics course. All activities revolve around the same data set collected early in the course. The activities require students to make decisions about how they should proceed.
KeepingUp with theWords: ExpressivePhraseOverlapping in theLateItalianMadrigal
Authors: TURCI‐ESCOBAR JOHN
Published: June 2012

For madrigal composers making every effort to follow the words, the transition from one phrase to the next presented a stumbling block. Transitions in sixteenth‐century polyphony typically feature a cadence in the exiting phrase and a new point of imitation in the approaching phrase. These events not only interrupt the rate of motion, but also create a musical space which is expressively neutral. In the borderlands between adjacent phrases, therefore, the music often lags behind the verbal text. The present study calls attention to a special type of phrase overlapping, one which brings extra‐musical resonance to the areas between one phrase and the next. In expressive phrase overlapping, one or more entries of a new phrase introduce music‐rhetorical devices among the closing gestures of the outgoing phrase. The commentary focusses on four types of expressive phrase overlapping, each involving one type of text‐expressive licence: dissonance, false relations, chromatic semitones and dissonant leaps. More broadly, the argument attempts to ground analytical enquiry in questions which reflect the aesthetic concerns of the musical culture that produced and received the late madrigal.
Dehydroepiandrosterone replacement therapy in older adults improves indices of arterial stiffness
Authors: Weiss Edward P. , Villareal Dennis T. , Ehsani Ali A. , Fontana Luigi , Holloszy John O.
Published: June 2012

Serum dehydroepiandrosterone (DHEA) concentrations decrease approximately 80% between ages 25 and 75 year. Aging also results in an increase in arterial stiffness, which is an independent predictor of cardiovascular disease (CVD) risk and mortality. Therefore, it is conceivable that DHEA replacement in older adults could reduce arterial stiffness. We sought to determine whether DHEA replacement therapy in older adults reduces carotid augmentation index (AI) and carotid–femoral pulse wave velocity (PWV) as indices of arterial stiffness. A randomized, double‐blind trial was conducted to study the effects of 50 mg day−1 DHEA replacement on AI (n = 92) and PWV (n = 51) in women and men aged 65–75 year. Inflammatory cytokines and sex hormones were measured in fasting serum. AI decreased in the DHEA group, but not in the placebo group (difference between groups, −6 ± 2 AI units, P = 0.002). Pulse wave velocity also decreased (difference between groups, −3.5 ± 1.0 m s−1, P = 0.001); however, after adjusting for baseline values, the between‐group comparison became nonsignificant (P = 0.20). The reductions in AI and PWV were accompanied by decreases in inflammatory cytokines (tumor necrosis factor α and IL‐6, P < 0.05) and correlated with increases in serum DHEAS (r = −0.31 and −0.37, respectively, P < 0.05). The reductions in AI also correlated with free testosterone index (r = −0.23, P = 0.03). In conclusion, DHEA replacement in elderly men and women improves indices of arterial stiffness. Arterial stiffness increases with age and is an independent risk factor for CVD. Therefore, the improvements observed in this study suggest that DHEA replacement might partly reverse arterial aging and reduce CVD risk.
Service user perspectives of multiagency working: a qualitative study with children with educational and mental health difficulties and their parents
Authors: O'Reilly Michelle , Vostanis Panos , Taylor Helen , Day Crispin , Street Cathy , Wolpert Miranda
Published: June 2012

Background

Recent policies recommend effective joint working between health and education; however, the views of service users are underrepresented, particularly opinions of young children.

Method

The project was operational from 2005–2008 when interviews were conducted with parents and children. The children were attending CAMHS for mental health and educational difficulties.

Results

Results indicated that they had a positive view of multiagency working. They consider that joint working is limited by a number of problems and make recommendations for improvement.

Conclusions

Findings indicate that more effective communication between agencies is needed and this should be provided for parents in an accessible language. This has implications for training professionals together.
Upper Givetian and Frasnian (Middle and Upper Devonian) conodonts from Ampriú (Aragonian Pyrenees, Spain): global correlations and palaeogeographic relations
Authors: LIAO JAU‐CHYN , VALENZUELA‐RÍOS JOSÉ I.
Published: June 2012

Abstract:  This report describes for the first time a part of the Middle and Upper Devonian conodont sequence of the Sierra Negra Subfacies in the Aragonian Pyrenees (Spain), establishing the basis for further sound correlations both across the distinct Pyrenean facies and subfacies and on other relevant world areas. The description of 20 conodont taxa and their stratigraphical distribution permits recognition of two separate time intervals. The older one corresponds to the lower Upper Givetian (Middle Devonian), hermanni to cristatus ectypus zones. The younger interval is uppermost Lower Frasnian to lower Middle Frasnian (Upper Devonian) and is equivalent to MN4–MN6 zones. The combination of litho‐ and conodont biofacies supports the distinction between the Sierra Negra and Renanué Subfacies. Conodont biofacies for the studied interval are partially close to the ones from the Compte Subfacies, but lithofacies are clearly different. This faunal similarity fosters accurate correlation between subfacies and stimulates further research aiming at Devonian Pyrenean basin(s) reconstruction. Additionally, this faunal sequence permits direct comparison with regions located in northern Gondwana and in the Russian platform for part of the interval. Comparison with Laurasia, mainly with the Northwest Territories of Canada and the north‐western United States, is also provided. Some taxa are also common with eastern and central Asia (China, Siberia, Tadzhikistan, Afghanistan), Australia and western USA (Nevada).
Proterochampsa barrionuevoi (Archosauriformes: Proterochampsia) from the Late Triassic (Carnian) of Argentina and a phylogenetic analysis of Proterochampsia
Authors: DILKES DAVID , ARCUCCI ANDREA
Published: June 2012

Abstract:  Restudy of skulls and available postcrania of the proterochampsian archosauriform Proterochampsa barrionuevoi from the Ischigualasto Formation (Upper Triassic, Carnian) in the San Juan Province, Argentina, confirms that the genus is diagnosed by autapomorphies that include dermal sculpturing consisting of prominent ridges and nodular protuberances, a large hook‐like lateral projection on the quadratojugal, an antorbital fossa restricted to a depression along the maxilla, lateral expansion of the premaxilla anterior to the premaxilla–maxilla contact, absence of a supratemporal fossa, exclusion of jugal from suborbital fenestra, basal tubera of parabasisphenoid facing ventrally and reaching laterally beyond the basipterygoid process, and a ventral lamina on the angular. Proterochampsa nodosa is a valid species distinguished from P. barrionuevoi by fewer cranial ridges with larger protuberances, relatively smaller supratemporal fenestrae and width of frontals between orbits less than that of the nasals. A phylogenetic analysis supports the monophyly of Proterochampsia consisting of Proterochampsa, Chanaresuchus bonapartei, Gualosuchus reigi, Tropidosuchus romeri and Cerritosaurus binsfeldi. A temporal separation between the two basal proterochampsians with earliest records in the Late Triassic (Proterochampsa and Cerritosaurus) and Chanaresuchus, Gualosuchus and Tropidosuchus in the Middle Triassic indicates hidden proterochampsian diversity in the Middle Triassic.
INEQUALITY COMPARISONS IN A MULTI‐PERIOD FRAMEWORK: THE ROLE OF ALTERNATIVE WELFARE METRICS
Authors: CREEDY JOHN , HALVORSEN ELIN , THORESEN THOR O.
Published: June 2012

This paper considers the use of alternative welfare metrics in evaluations of income inequality in a multi‐period context. Using Norwegian longitudinal income data, it is found, as in many studies, that inequality is lower when each individual's annual average income is used as welfare metric, compared with the use of a single‐period accounting framework. However, this result does not necessarily hold when aversion to income fluctuations is introduced. Furthermore, when actual incomes are replaced by expected incomes (conditional on an initial period), using a model of income dynamics, higher values of inequality over longer periods are typically found, although comparisons depend on inequality and variability aversion parameters. The results are strongly influenced by the observed high degree of systematic regression toward the (geometric) mean, combined with a large extent of individual unexpected effects.
Ligand‐directed signalling within the opioid receptor family
Authors: Pradhan Amynah A , Smith Monique L , Kieffer Brigitte L , Evans Christopher J
Published: June 2012

The classic model of GPCR activation proposed that all agonists induce the same active receptor conformation. However, research over the last decade has shown that GPCRs exist in multiple conformations, and that agonists can stabilize different active states. The distinct receptor conformations induced by ligands result in distinct receptor–effector complexes, which produce varying levels of activation or inhibition of subsequent signalling cascades. This concept, referred to as ligand‐directed signalling or biased agonism has important biological and therapeutic implications. Opioid receptors are Gi/o GPCRs and regulate a number of important physiological functions, including pain, reward, mood, stress, gastrointestinal transport and respiration. A number of in vitro studies have shown biased agonism at the three opioid receptors (µ, δ and κ); however, in vivo consequences of this phenomenon have only recently been demonstrated. For the µ and δ opioid receptors, the majority of reported ligand selective behavioural effects are observed as differential adaptations to repeated drug administration. In terms of the κ opioid receptor, clear links between ligand‐selective signalling events and specific in vivo responses have been recently characterized. Drugs for all three receptors are either already used or are being developed for clinical applications. There is clearly a need to better characterize the specific events that occur following agonist stimulation and how these relate to in vivo responses. This understanding could eventually lead to the development of tailor‐made pharmacotherapies where advantageous drug effects can be selectively targeted over adverse effects.
A methodological approach to assessing alveolar ridge preservation procedures in humans: hard tissue profile
Authors: Lambert France , Vincent Kim , Vanhoutte Vanessa , Seidel Laurence , Lecloux Geoffrey , Rompen Eric
Published: June 2012

Aims

Multiple surgical protocols using biomaterials have been proposed to limit the typical post‐extraction bone resorption. However, because of the heterogeneity of the studies, particularly the differences in assessment methods, it is difficult to determine the superiority of one technique over another. The objective of this study was to describe a new radiographic method to draw a map of alveolar bone remodelling after alveolar ridge preservation procedures to compare different surgical techniques more accurately. The newly developed measuring method was applied to a case series describing a specific preservation technique.

Materials and Methods

Fourteen extraction sites (in 14 patients) located in the upper anterior maxilla were treated with bovine hydroxyapatite (0.25‐ to 1‐mm particles) and a saddled connective tissue graft. A radiographic three‐dimensional assessment of the hard tissues was performed at baseline and 3 months after the procedure. Standardized horizontal measurements were taken at three corono‐apical levels (−2, −5 and −9 mm) and at three mesio‐distal levels (mesial, centre and distal) in the buccal and palatal aspects. Vertical measurements were also recorded in nine regions superior to the alveolar crest. The measurements were performed by two independent observers and intra‐ and inter‐observer effects were evaluated.

Results

No inter‐ and intra‐observer effects were found when analysing the measurements from these two observers. The horizontal dimension of the crest decreased by 1.6 mm (20%) in the cervical regions (−2 mm level), decreased moderately, by 1 mm (12%), at the −5 mm level and decreased very little, 0.5 mm (6%), at the apical (−8 mm) level. The losses were always significantly higher in the buccal than in the palatal aspect. Buccally, the maximal bone remodelling at the cervical level remained below 1 mm. Vertical bone resorption was homogeneous and<1 mm in the nine measured regions.

Discussion

The radiographic measuring methodology proved to be reproducible. It can be applied in other clinical settings. It successfully assessed the alveolar ridge preservation technique (BHA+saddle connective tissue graft).
Proteomic analysis of Porphyromonas gingivalis exposed to nicotine and cotinine
Authors: Cogo K. , de Andrade A. , Labate C. A. , Bergamaschi C. C. , Berto L. A. , Franco G. C. N. , Gonçalves R. B. , Groppo F. C.
Published: June 2012

Cogo K, de Andrade A, Labate CA, Bergamaschi CC, Berto LA, Franco GCN, Gonçalves RB, Groppo FC. Proteomic analysis of Porphyromonas gingivalis exposed to nicotine and cotinine. J Periodont Res 2012; 47: 766–775. © 2012 John Wiley & Sons A/S

Background and Objective:  Smokers are more predisposed than nonsmokers to infection with Porphyromonas gingivalis, one of the most important pathogens involved in the onset and development of periodontitis. It has also been observed that tobacco, and tobacco derivatives such as nicotine and cotinine, can induce modifications to P. gingivalis virulence. However, the effect of the major compounds derived from cigarettes on expression of protein by P. gingivalis is poorly understood. Therefore, this study aimed to evaluate and compare the effects of nicotine and cotinine on the P. gingivalis proteomic profile.

Material and Methods:  Total proteins of P. gingivalis exposed to nicotine and cotinine were extracted and separated by two‐dimensional electrophoresis. Proteins differentially expressed were successfully identified through liquid chromatography‐mass spectrometry and primary sequence databases using MASCOT search engine, and gene ontology was carried out using DAVID tools.

Results:  Of the approximately 410 protein spots that were reproducibly detected on each gel, 23 were differentially expressed in at least one of the treatments. A particular increase was seen in proteins involved in metabolism, virulence and acquisition of peptides, protein synthesis and folding, transcription and oxidative stress. Few proteins showed significant decreases in expression; those that did are involved in cell envelope biosynthesis and proteolysis and also in metabolism.

Conclusion:  Our results characterized the changes in the proteome of P. gingivalis following exposure to nicotine and cotinine, suggesting that these substances may modulate, with minor changes, protein expression. The present study is, in part, a step toward understanding the potential smoke–pathogen interaction that may occur in smokers with periodontitis.