bluuebunny/crossref_metadata_2025 huggingface dataset:
Mexiletine as a treatment for primary erythromelalgia: normalization of biophysical properties of mutant L858F NaV1.7 sodium channels
Authors: Cregg R , Cox J J , Bennett D L H , Wood J N , Werdehausen R
Published: May 2014

Background and Purpose

The non‐selective sodium channel inhibitor mexiletine has been found to be effective in several animal models of chronic pain and has become popular in the clinical setting as an orally available alternative to lidocaine. It remains unclear why patients with monogenic pain disorders secondary to gain‐of‐function SCN9a mutations benefit from a low systemic concentration of mexiletine, which does not usually induce adverse neurological side effects. The aim of this study was, therefore, to investigate the biophysical effects of mexiletine on the L858F primary erythromelalgia NaV1.7 mutation in vitro.

Experimental Approach

Human wild‐type and L858F‐mutated NaV1.7 channels were expressed in HEK293A cells. Whole‐cell currents were recorded by voltage‐clamp techniques to characterize the effect of mexiletine on channel gating properties.

Key Results

While the concentration‐dependent tonic block of peak currents by mexiletine was similar in wild‐type and L858F channels, phasic block was more pronounced in cells transfected with the L858F mutation. Moreover, mexiletine substantially shifted the pathologically‐hyperpolarized voltage‐dependence of steady‐state activation in L858F‐mutated channels towards wild‐type values and the voltage‐dependence of steady‐state fast inactivation was shifted to more hyperpolarized potentials, leading to an overall reduction in window currents.

Conclusion and Implications

Mexiletine has a normalizing effect on the pathological gating properties of the L858F gain‐of‐function mutation in NaV1.7, which, in part, might explain the beneficial effects of systemic treatment with mexiletine in patients with gain‐of‐function sodium channel disorders.
Pharmacological manipulations in animal models of anorexia and binge eating in relation to humans
Authors: van Gestel M A , Kostrzewa E , Adan R A H , Janhunen S K
Published: May 2014

Eating disorders, such as anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorders (BED), are described as abnormal eating habits that usually involve insufficient or excessive food intake. Animal models have been developed that provide insight into certain aspects of eating disorders. Several drugs have been found efficacious in these animal models and some of them have eventually proven useful in the treatment of eating disorders. This review will cover the role of monoaminergic neurotransmitters in eating disorders and their pharmacological manipulations in animal models and humans. Dopamine, 5‐HT (serotonin) and noradrenaline in hypothalamic and striatal regions regulate food intake by affecting hunger and satiety and by affecting rewarding and motivational aspects of feeding. Reduced neurotransmission by dopamine, 5‐HT and noradrenaline and compensatory changes, at least in dopamine D2 and 5‐HT2C/2A receptors, have been related to the pathophysiology of AN in humans and animal models. Also, in disorders and animal models of BN and BED, monoaminergic neurotransmission is down‐regulated but receptor level changes are different from those seen in AN. A hypofunctional dopamine system or overactive α2‐adrenoceptors may contribute to an attenuated response to (palatable) food and result in hedonic binge eating. Evidence for the efficacy of monoaminergic treatments for AN is limited, while more support exists for the treatment of BN or BED with monoaminergic drugs.

Linked Articles

This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20
Maternal and child health nurses' self‐perceived confidence in dealing with child behaviour problems
Authors: Sarkadi A. , Gulenc A. , Hiscock H.
Published: May 2014

Background

Addressing behaviour problems in children is increasingly becoming part of routine care. The question therefore arises as to which workforce members are best suited to deliver structured interventions and what skill sets they might need apart from knowledge of the specific parenting programme offered.

Objectives

To assess maternal and child health (MCH) nurses' self‐perceived confidence in dealing with child behaviour problems.

Design

Cross‐sectional questionnaire study. Data collection occurred prior to cluster randomization in the Families in Mind trial.

Setting

MCH clinics in nine local government areas in greater Melbourne, in 2010.

Participants

All MCH nurses in the nine areas were invited to participate, 153 (79%) completed the survey.

Main outcomes measures

Nurses' comfort, competency, attitudes and perceived difficulties in dealing with child behaviour problems.

Results

The majority of nurses (63%) viewed it as their role to deal with, rather than refer, child behaviour problems and felt that the task was rewarding (86%). They believed that parenting advice should be offered universally, rather than only to families with severe problems (94%). Nurses felt rather comfortable and competent to broach and discuss child behaviour problems without need for prior parental request, but somewhat less comfortable and competent to manage child behaviour problems or to make a difference. Experienced nurses (>10 years in practice) felt more comfortable and competent. Nurses described that the major challenge in their dealing with child behaviour problems was parental denial or resistance (60%).

Conclusions

MCH nurses are at the frontline of preventive medical services for families with young children where behaviour problems are a common concern. Because managing young children's behaviour problems primarily occurs through adult behaviour change, techniques addressing parent denial and non‐compliance, such as motivational interviewing and empowerment should be a part of MCH nurses' skill sets.
Associations between early alcohol and tobacco use and prolonged time to puberty in boys
Authors: Davis E. M. , Peck J. D. , Peck B. M. , Kaplan H. B.
Published: May 2014

Background

Previous research has demonstrated a relationship between prepubertal alcohol and tobacco use and delayed pubertal characteristics in girls. Although, laboratory research indicates that alcohol and tobacco use inhibits sexual maturation in male rats, human research in this area is lacking. To address this question among boys, we conducted a study to explore the association between early use of alcohol and tobacco and time to development of secondary sexual characteristics.

Methods

The study population included 3199 boys interviewed between the ages of 11 and 21. Participants reported the ages at which they first experienced body hair growth, deepening of the voice and facial hair growth. Early alcohol and tobacco use were defined as first use preceding the age of pubertal development among those reporting regular consumption patterns. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazard models.

Results

Early alcohol use was associated with longer time to body hair growth (HR 0.77; 95% CI 0.69–0.87), voice changes (HR 0.72; 95% CI 0.64–0.82) and facial hair growth (HR 0.77; 95% CI 0.68–0.86), after adjusting for tobacco use and age at interview. Tobacco use was not independently associated with the puberty indicators after controlling for alcohol use and age at interview.

Conclusions

Our findings are consistent with the hypothesis that alcohol may inhibit puberty onset in boys, an association that has been previously observed among young girls. Thus, alcohol may be an exposure deserving more scrutiny as a disruptor to normal pubertal development.
Internal bacterial colonization of implants: association with peri‐implant bone loss
Authors: Jervøe‐Storm Pia‐Merete , Jepsen Søren , Jöhren Peter , Mericske‐Stern Regina , Enkling Norbert
Published: May 2014

Objectives

The aim of the present longitudinal study was to investigate bacterial colonization of the internal implant cavity and to evaluate a possible association with peri‐implant bone loss.

Methods

A total of 264 paper point samples were harvested from the intra‐implant cavity of 66 implants in 26 patients immediately following implant insertion and after 3, 4, and 12 months. Samples were evaluated for Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola, and Tannerella forsythia as well as total bacterial counts by real‐time PCR. Bone loss was evaluated on standardized radiographs up to 25 months after implant insertion. For the statistical analysis of the data, mixed effects models were fitted.

Results

There was an increase in the frequency of detection as well as in the mean counts of the selected bacteria over time. The evaluation of the target bacteria revealed a significant association of Pr. intermedia at 4 and 12 months with peri‐implant bone loss at 25 months (4 months: P = 0.009; 12 months: P = 0.021).

Conclusions

The present study could demonstrate a progressive colonization by periodontopathogenic bacteria in the internal cavities of two‐piece implants. The results suggest that internal colonization with Pr. intermedia was associated with peri‐implant bone loss.
Functional connectivity in prenatally stressed rats with and without maternal treatment with ladostigil, a brain‐selective monoamine oxidase inhibitor
Authors: Goelman G. , Ilinca R. , Zohar I. , Weinstock M.
Published: May 2014

Stress during pregnancy in humans is known to be a risk factor for neuropsychiatric disorders in the offspring. Prenatal stress in rats caused depressive‐like behavior that was restored to that of controls by maternal treatment with ladostigil (8.5 mg/kg per day), a brain‐selective monoamine oxidase (MAO) inhibitor that prevented increased anxiety‐like behavior in stressed mothers. Ladostigil inhibited maternal striatal MAO‐A and ‐B by 45–50% at the time the pups were weaned. Using resting state‐functional connectivity magnetic resonance imaging on rat male offspring of control mothers, and mothers stressed during gestation with and without ladostigil treatment, we identified neuronal connections that differed between these groups. The percentage of significant connections within a predefined predominantly limbic network in control rats was 23.3 within the right and 22.0 within the left hemisphere. Prenatal stress disturbed hemispheric symmetry, resulting in 30.2 and 21.6%, significant connections in the right and left hemispheres, respectively, but this was fully restored in the maternal ladostigil group to 24.6% in both hemispheres. All connections that were modified in prenatally stressed rats and restored by maternal drug treatment were associated with the dopaminergic system. Specifically, we observed that restoration of the connections of the right nucleus accumbens shell with frontal areas, the cingulate, septum and motor and sensory cortices, and those of the right globus pallidus with the infra‐limbic and the dentate gyrus, were most important for prevention of depressive‐like behavior.
The skin microbiome of caspase‐14‐deficient mice shows mild dysbiosis
Authors: Kubica Malgorzata , Hildebrand Falk , Brinkman Brigitta M. , Goossens Dirk , Del Favero Jurgen , Vercammen Ken , Cornelis Pierre , Schröder Jens‐Michael , Vandenabeele Peter , Raes Jeroen , Declercq Wim
Published: May 2014

Caspase‐14, an important proteinase involved in filaggrin catabolism, is mainly active in terminally differentiating keratinocytes, where it is required for the generation of skin natural moisturizing factors (NMFs). Consequently, caspase‐14 deficient epidermis is characterized by reduced levels of NMFs such as urocanic acid and 2‐pyrrolidone‐5‐carboxylic acid. Patients suffering from filaggrin deficiency are prone to develop atopic dermatitis, which is accompanied with increased microbial burden. Among several reasons, this effect could be due to a decrease in filaggrin breakdown products. In this study, we found that caspase‐14−/− mice show enhanced antibacterial response compared to wild‐type mice when challenged with bacteria. Therefore, we compared the microbial communities between wild‐type and caspase‐14−/− mice by sequencing of bacterial 16S ribosomal RNA genes. We observed that caspase‐14 ablation leads to an increase in bacterial richness and diversity during steady‐state conditions. Although both wild‐type and caspase‐14−/− skin were dominated by the Firmicutes phylum, the Staphylococcaceae family was reduced in caspase‐14−/− mice. Altogether, our data demonstrated that caspase‐14 deficiency causes the imbalance of the skin‐resident bacterial communities.
Resveratrol attenuates bone cancer pain through the inhibition of spinal glial activation and CX3CR1 upregulation
Authors: Cheng Wei , Zhao Yu , Liu He , Fan Qin , Lu Fei‐Fei , Li Jing , Yin Qin , Yan Chang‐Dong
Published: May 2014

The present study examined the effects of intrathecal use of resveratrol on pain hypersensitivities, spinal glia activation, and CX3CR1 expression in the model of bone cancer pain (BCP). The BCP model was established through intrathecally injecting Walker 256 mammary gland carcinoma cells to Sprague‐Dawley rats. We found that spinal CX3CR1 expression and glial activation aggravated after inoculation. Resveratrol (i.t.) attenuated bone cancer‐induced pain hypersensitivities, decreased CX3CR1 expression and glial activation in the spine in a BCP model. Resveratrol (i.t.) also attenuated mechanical allodynia resulting from intrathecally injecting fractalkine in rats. Inhibition of spinal glial activation and CX3CR1 upregulation may involve in resveratrol's analgesic effects. These findings demonstrated that resveratrol attenuated pain facilitation through inhibiting spinal glial activation and CX3CR1 upregulation in a BCP model.
Precipitation and winter temperature predict long‐term range‐scale abundance changes in Western North American birds
Authors: Illán Javier Gutiérrez , Thomas Chris D. , Jones Julia A. , Wong Weng‐Keen , Shirley Susan M. , Betts Matthew G.
Published: May 2014

Predicting biodiversity responses to climate change remains a difficult challenge, especially in climatically complex regions where precipitation is a limiting factor. Though statistical climatic envelope models are frequently used to project future scenarios for species distributions under climate change, these models are rarely tested using empirical data. We used long‐term data on bird distributions and abundance covering five states in the westernUSand in the Canadian province of British Columbia to test the capacity of statistical models to predict temporal changes in bird populations over a 32‐year period. Using boosted regression trees, we built presence‐absence and abundance models that related the presence and abundance of 132 bird species to spatial variation in climatic conditions. Presence/absence models built using 1970–1974 data forecast the distributions of the majority of species in the later time period, 1998–2002 (meanAUC = 0.79 ± 0.01). Hindcast models performed equivalently (meanAUC = 0.82 ± 0.01). Correlations between observed and predicted abundances were also statistically significant for most species (forecast mean Spearman′sρ = 0.34 ± 0.02, hindcast = 0.39 ± 0.02). The most stringent test is to test predicted changes in geographic patterns through time. Observed changes in abundance patterns were significantly positively correlated with those predicted for 59% of species (mean Spearman′sρ = 0.28 ± 0.02, across all species). Three precipitation variables (for the wettest month, breeding season, and driest month) and minimum temperature of the coldest month were the most important predictors of bird distributions and abundances in this region, and hence of abundance changes through time. Our results suggest that models describing associations between climatic variables and abundance patterns can predict changes through time for some species, and that changes in precipitation and winter temperature appear to have already driven shifts in the geographic patterns of abundance of bird populations in western North America.
Can trait‐based analyses of changes in species distribution be transferred to new geographic areas?
Authors: Powney Gary D. , Preston Christopher D. , Purvis Andy , Van Landuyt Wouter , Roy David B.
Published: May 2014

Aim

Anthropogenic environmental change is having a major impact on biodiversity. By identifying traits that correlate with changes in species range, comparative studies can shed light on the mechanisms driving this change; but such studies will be more useful for conservation if they have true predictive power, i.e. if their trait‐based models can be transferred to new regions. We aim to examine the ability of trait‐based models to predict changes in plant distribution across seven geographic regions that varied in terms of land cover and species composition.

Location

Britain and Flanders (Belgium).

Methods

We estimated distribution change for more than 1000 species for over 70 years of data (1930s to 2004), using data from published plant atlases. We identified regional trait‐based models of plant distribution change. Traits included morphological characteristics, Ellenberg values and distribution‐based traits. The trait models were then used to predict change in all other regions, with the level of linear correlation between predicted and observed changes in range used as a measure of transferability. We then related transferability to land cover and species similarity between regions.

Results

We found that trait correlates of range change varied regionally, highlighting the regional variation in the drivers of range change in plants. These trait models also varied in the amount of variation explained, with r2 values ranging from 0.05 to 0.17. A key cross‐regional difference was the variation in the relationship between soil nutrient association (Ellenberg N) and distribution change, which was strongly positive in Flanders and southern England but significantly negative in northern Scotland. We found that transferability between regions was significantly correlated with the level of similarity in land cover.

Main conclusions

We conclude that trait‐based models can predict broad‐scale changes in species distributions in regions that share similar land‐cover composition; however, predictions between regions with differing land‐cover cover tend to be poor.
On the measurement of dimensionality of biodiversity
Authors: Stevens Richard D. , Tello J. Sebastián
Published: May 2014

Aim

To characterize relationships among indices of taxonomic, phylogenetic, functional and phenetic diversity (TPFP diversity) for Neotropical bats and examine if dimensionality is different from null model expectations after controlling for sampling effects owing to underlying variation in species richness.

Location

Neotropics.

Methods

Bat distributions were estimated using geographic range maps. By overlaying range maps on a gridded map of the New World, the species composition of each cell was determined. Then, species richness and three indices each of phylogenetic, functional and phenetic diversity were calculated. A principal components analysis (PCA) determined the dimensionality of the entire multivariate data set. This was followed by two additional PCAs that examined the dimensionality of spatial and non‐spatial fractions of the original data. Spearman rank correlations determined pair‐wise association among indices. Correlations and dimensionality were compared with two different null models that account for species richness gradients.

Results

Ten measures characterizing TPFP diversity exhibited much spatial structure across the New World. Pair‐wise correlations between indices were typically different from null model expectations. While patterns of multivariate covariation were similar across spatial and non‐spatial data sets, the dimensionality of biodiversity was low and either lower than or no different from null model expectations.

Main conclusions

Most measures of biodiversity exhibit at least some level of quantitative redundancy, and this redundancy is often higher than expected given sampling effects owing to species richness gradients. Considerations of uniqueness should be made when examining conceptually different dimensions of biodiversity.
Ambiguous biogeographical patterns mask a more complete understanding of the Ordovician to Devonian evolution of Japan
Authors: Williams Mark , Wallis Simon , Oji Tatsuo , Lane Philip D.
Published: May 2014

Fossil assemblages of the Ordovician to Devonian successions of Japan suggest complex temporal, environmental and geographical controls on their biogeographical signature. Thus, limited similarity at the species‐level between the trilobite, brachiopod and ostracod faunas of the South Kitakami, Hida‐Gaien and Kurosegawa terranes in part reflects the sporadic stratigraphic distribution of shelly fauna within these terranes. As a result, and with the exception of corals and pan‐tropical radiolarians, species‐level similarities are greater with other regions of East Asia and Australia than amongst the Japanese terranes. The Silurian faunas of the South Kitakami Terrane have affinities with North America, Europe, Central Asia and Australia, but there is no overriding signature to support proximity either to South China or Gondwana. Notably, brachiopod and trilobite faunas of the Middle Devonian suggest strong connections with North China. Trilobite, coral and ostracod faunas of the Hida‐Gaien Terrane show affinity, including at species level, with Siluro‐Devonian faunas from westerly‐situated palaeocontinents, especially those of Central Asian and European affinity, suggesting a continuation of the Central Asian Orogenic Belt, or of its associated lithofacies. Greater diversity of groups such as ostracods and trilobites in this terrane may signal closer links with continental shelf faunas of East Asia. The dominant biogeographical signature of the Kurosegawa Terrane is from corals and trilobites, suggesting links with the Siluro‐Devonian of Central Asia, Australia and South China. The variable biogeographic signal of the Japanese faunas may reflect the lifestyles of organisms with different physiologies and larval dispersal mechanisms, as well as the relative incompleteness of the Japanese fossil record. The present state of knowledge of the faunas cautions against placing Japan in relative proximity to the North or South China plates, or of presenting the Japanese terranes as a unified island arc to the north of the South China Plate during the Early Palaeozoic.
Chemically Strengthened Low Crystallinity Black Glass‐Ceramics with High Liquidus Viscosities
Authors: Dejneka Matthew , Dutta Indrajit , Smith Charlene
Published: May 2014

Strong, black materials are needed for electronic device backs and appliance facings. While glass‐ceramics have good strength and toughness, their liquidus viscosity is too low to enable economical forming of these devices by the fusion or slot draw methods. Thus, we invented a new class of low crystallinity glass‐ceramics with 10–20 nm crystallites in the Fe2O3‐TiO2‐MgO system. These materials were formed into transparent glasses and then heat treated to make black opaque glass‐ceramics containing magnetite, pseudobrookite, and/or ε‐Fe2O3. The ε‐Fe2O3 phase exhibited extensive solid solution (ss) between Fe2O3 and MgTiO3. The blackness and opacity of the ε‐Fe2O3 glass‐ceramics peaked at a ceram temperature of 750°C where the Fe2+ in the crystallites was maximized, resulting in peak Fe2+‐Ti4+ charge transfer absorption. The liquidus viscosity was increased to more than 100 kPa*s by optimizing the base glass composition and minimizing the amount of crystallinity, thereby enabling fusion formability. These fusion formable glass‐ceramics had strengths exceeding the best commercially available glasses after ion exchange. This work provides a new class of low crystallinity fusion formable glass‐ceramics with high strength.
Knockdown of mitogen‐activated protein kinase (MAPK) signalling in the midgut of Anopheles stephensi mosquitoes using antisense morpholinos
Authors: Pietri J. E. , Cheung K. W. , Luckhart S.
Published: May 2014

Arthropod‐borne infectious diseases are responsible for nearly 1.5 million deaths annually across the globe, with malaria responsible for >50% of these deaths. Recent efforts to enhance malaria control have focused on developing genetically modified Anopheles mosquitoes that are resistant to malaria parasite infection by manipulating proteins that are essential to the immune response. Although this approach has shown promise, the lack of efficient genetic tools in the mosquito makes it difficult to investigate innate immunity using reverse genetics. Current gene knockdown strategies based on small interfering RNA are typically labourious, inefficient, and require extensive training. In the present study, we describe the use of morpholino antisense oligomers to knockdown MEK‐ERK signalling in the midgut of Anopheles stephensi through a simple feeding protocol. Anti‐MEK morpholino provided in a saline meal was readily ingested by female mosquitoes with minimal toxicity and resulted in knockdown of total MEK protein levels 3–4 days after morpholino feeding. Further, anti‐MEK morpholino feeding attenuated inducible phosphorylation of the downstream kinase ERK and, as predicted by previous work, reduced parasite burden in mosquitoes infected with Plasmodium falciparum. To our knowledge, this is the first example of morpholino use for target protein knockdown via feeding in an insect vector. Our results suggest this method is not only efficient for studies of individual proteins, but also for studies of phenotypic control by complex cell signalling networks. As such, our protocol is an effective alternative to current methods for gene knockdown in arthropods.
Do Pathways Matter? Linking Early Immigrant Employment Sequences and Later Economic Outcomes: Evidence from Canada
Authors: Fuller Sylvia
Published: May 2014

Employment mobility is a critical feature of immigrants’ settlement experiences and longer-term life chances. While current research typically treats mobility as a singular outcome, becoming established in a new labor market is a complex process that can entail multiple transitions in and out of employment and between different types of jobs over time. This article advances understanding of the process of immigrant labor market incorporation by engaging with its potentially multidimensional, cumulative, and path-dependent aspects. Using data from the Longitudinal Survey of Immigrants to Canada, I test the impact of an empirically derived typology of month-by-month immigrant employment trajectories on the odds of occupational degradation and on weekly wages. I find that the pathways immigrants take through the labor market in their first four years constitute a distinct and important mechanism shaping later employment outcomes.
Thermal Expansion of HfO2 and ZrO2
Authors: Haggerty Ryan P. , Sarin Pankaj , Apostolov Zlatomir D. , Driemeyer Patrick E. , Kriven Waltraud M.
Published: May 2014

The thermal expansion of a low symmetry crystal can be much more interesting than the lattice parameter expansion would suggest. Here, the complete thermal expansion tensors for monoclinic and tetragonal phases of ZrO2 and HfO2 have been measured in air, by high‐resolution, high‐temperature X‐ray diffraction. These results reveal the highly anisotropic nature of thermal expansion in the monoclinic phase as well as a cooperative movement of ions and the existence of a zero thermal expansion plane.
Long‐term effects of stock transfers: synergistic introgression of allochthonous genomes in salmonids
Authors: Horreo J. L. , Machado‐Schiaffino G. , Griffiths A. M. , Bright D. , Stevens J. R. , Garcia‐Vazquez E.
Published: May 2014

The genus Salmo was employed as a model to study introgression of genes between species due to secondary contacts. Seven microsatellite loci, the LDH‐C1* locus and the 5S ribosomal DNA were studied. Results showed the mutually enhanced introgression of allochthonous genomes into southern European salmonids. This phenomenon appears to go beyond a simple consequence of the altered behaviour of domestic individuals. Invasions of autochthonous genomes by allochthonous genes would be enhanced by human activities such as stock transfers, which would simultaneously promote allochthonous and allospecific (from other species) introgressions in a synergistic process in Atlantic salmon Salmo salar and brown trout Salmo trutta. As a minor result, the data do not support the value of the microsatellite locus SsaD486 as a species‐specific marker.
Astrocyte‐dependent protective effect of quetiapine on GABAergic neuron is associated with the prevention of anxiety‐like behaviors in aging mice after long‐term treatment
Authors: Wang Junhui , Zhu Shenghua , Wang Hongxing , He Jue , Zhang Yanbo , Adilijiang Abulimiti , Zhang Handi , Hartle Kelly , Guo Huining , Kong Jiming , Huang Qingjun , Li Xin‐Min
Published: May 2014

Previous studies have demonstrated that quetiapine (QTP) may have neuroprotective properties; however, the underlying mechanisms have not been fully elucidated. In this study, we identified a novel mechanism by which QTP increased the synthesis of ATP in astrocytes and protected GABAergic neurons from aging‐induced death. In 12‐month‐old mice, QTP significantly improved cell number of GABAegic neurons in the cortex and ameliorated anxiety‐like behaviors compared to control group. Complimentary in vitro studies showed that QTP had no direct effect on the survival of aging GABAergic neurons in culture. Astrocyte‐conditioned medium (ACM) pretreated with QTP (ACMQTP) for 24 h effectively protected GABAergic neurons against aging‐induced spontaneous cell death. It was also found that QTP boosted the synthesis of ATP from cultured astrocytes after 24 h of treatment, which might be responsible for the protective effects on neurons. Consistent with the above findings, a Rhodamine 123 test showed that ACMQTP, not QTP itself, was able to prevent the decrease in mitochondrial membrane potential in the aging neurons. For the first time, our study has provided evidence that astrocytes may be the conduit through which QTP is able to exert its neuroprotective effects on GABAergic neurons.

image

The neuroprotective properties of quetiapine (QTP) have not been fully understood. Here, we identify a novel mechanism by which QTP increases the synthesis of ATP in astrocytes and protects GABAergic neurons from aging‐induced death in a primary cell culture model. In 12‐month‐old mice, QTP significantly improves cell number of GABAegic neurons and ameliorates anxiety‐like behaviors. Our study indicates that astrocytes may be the conduit through which QTP exerts its neuroprotective effects on GABAergic neurons.
Occlusal Rehabilitation of Pseudo‐Class III Patient
Authors: Cardoso Antônio Carlos , Ferreira Cimara Fortes , Oderich Elisa , Pedroso Moira Leão , Wicks Russell
Published: May 2014

To treat a patient with anterior crossbite, the clinician should first assess if it is a genuine class III or a pseudo‐class III malocclusion. Cephalometric analysis is important; however, registering a patient's centric relation (CR) is simple, quick, and costless and can play a decisive role in a differential diagnosis for this type of patient profile. This clinical report depicts a patient clinically diagnosed as class III. After mandible manipulation in CR, it was noted that the patient in question was a pseudo‐class III. The treatment was based on the pseudo‐class III diagnosis. Therefore, the patient was rehabilitated by occlusal adjustments and conventional and implant‐supported prostheses and without the need for invasive orthognathic surgery.
Imperfect Bundling in Public–Private Partnerships
Authors: GRECO LUCIANO
Published: May 2014

We provide a first contribution to analyze how agency problems within the private consortium (i.e., imperfect bundling of private tasks) affect the performance of public–private partnerships (PPPs). When both public–private and private–private contracts are incomplete, the profit‐sharing rules are key to regulate private partners' incentives. In failing to consider the role of imperfect bundling, the scope for PPPs may be overrated (or underrated) if the social benefits of infrastructure quality are large (or small) as compared to the social cost of operation efficiency. Also, it may be optimal for the government to restrict the admissible governance of private consortia.
Large‐Scale Risks and Technological Change: What About Limited Liability?
Authors: JACOB JULIEN , SPAETER SANDRINE
Published: May 2014

We consider a firm under strict liability that must choose between two risky technologies, one being safer but costlier than the other one. The total potential level of damage increases with the level of activity. We show that, under limited liability, technological change is welfare‐improving and leads to full risk internalization when the firms are sufficiently capitalized. Nevertheless, the percentage of firms adopting the safer technology and full risk internalization is higher under unlimited liability than under limited liability. We show how an adequate tax policy increases this percentage. We also determine the characteristics of a second‐best tax policy.
Genetically Diverse Variants of Sugarcane bacilliform virus Infecting Sugarcane in India and Evidence of a Novel Recombinant Badnavirus Variant
Authors: Rao Govind P. , Sharma Susheel K. , Singh Deepti , Arya Meenakshi , Singh Priyanka , Baranwal Virendra K.
Published: May 2014

Sugarcane bacilliform viruses (SCBV; genus Badnavirus) cause leaf fleck disease in sugarcane worldwide. SCBV was detected in 28 sugarcane cultivars originating from eight states of India. Eight representative SCBV isolates from five different states showed sequence variability up to 27% in the reverse transcriptase and RNase H (RT/RNase H) genetic region. Five isolates [SCBV‐AP (Co693077): HQ324248, SCBV‐Assam (CoBIN94063): HQ324246, SCBV‐Bihar (Bo141): HQ324245, SCBV‐UP (Co1424): KC013276 and SCBV‐UP (CoSe6460): KC013277] showed sequence identity of 86–88% with Sugarcane bacilliform IM virus (SCBIMV), but the other three isolates [SCBV‐Kerala (Co7219): HQ324249, SCBV‐TN (Co86032): GQ385038 and SCBV‐UP (CoSe92423): HQ324247] showed maximum sequence identity of 75–79% with Sugarcane bacilliform MO virus (SCBMOV). In phylogenetic analysis, the SCBV isolates segregated into two new subclades and were distinct from the known SCBV genotypes. The rates of non‐synonymous and synonymous (dN/dS) substitution indicated the signs of purifying selection with strong functional constraints for RT/RNase H region in SCBV population. A variant (SCBV‐UP, CoSe92423) was identified to be a recombinant isolate having two other Indian SCBV isolates as parents. Although RT/RNase H region is a recombination cold spot, a strong recombination might have played a key role in the evolution of this new variant of SCBV. Our study provides an insight into the diverse genetic structure of SCBV population and presence of a novel recombinant SCBV species/variant infecting sugarcane cultivars in India. Our results will be helpful in devising a robust detection procedure for quarantine and field testing of sugarcane germplasm.
Genetic Diversity and Pathogenicity of Fusarium oxysporum f.sp. melonis Races from Different Areas of Italy
Authors: Luongo Laura , Ferrarini Alberto , Haegi Anita , Vitale Salvatore , Polverari Annalisa , Belisario Alessandra
Published: May 2014

Fusarium wilt caused by Fusarium oxysporum f.sp. melonis (FOM) is a devastating disease of melon worldwide. Pathogenicity tests performed with F. oxysporum isolates obtained from Italian melon‐growing areas allowed to identify thirty‐four FOM isolates and the presence of all four races. The aims of this work were to examine genetic relatedness among FOM isolates by race determination and to perform phylogenetic analyses of identified FOM races including also other formae speciales of F. oxysporum of cucurbits. Results showed that FOM race 1,2 was the most numerous with a total of eighteen isolates, while six and nine isolates were identified as race 0 and 1, respectively, and just one isolate was assigned to race 2. Phylogenetic analysis was performed by random amplified polymorphic DNA (RAPD) profiling and by translation elongation factor‐1α (TEF‐1α) sequencing. The analysis of RAPD profiles separated FOM races into two distinct clades. Clade 1, which included races 0, 1 and 1,2, was further divided into ‘subclade a’ which grouped almost all race 1,2 isolates, and into ‘subclade b’ which included race 0 and 1 isolates. Clade 2 comprised only race 2 isolates. The phylogenetic analysis based on TEF‐1α separated FOM from the other formae speciales of F. oxysporum. Also with TEF‐1α analysis, FOM races 0, 1 and 1,2 isolates grouped in one single clade clearly separated from FOM race 2 isolates which grouped closer to F. oxysporum f.sp. cucumerinum. RAPD technique was more effective than TEF‐1α in differentiating FOM race 1,2 isolates from those belonging to the closely related races 0 and 1. Both phylogenetic analyses supported the close relationship between the three different FOM races which might imply the derivation from one another and the different origin of FOM race 2.
Phylogenetic study of Geitlerinema and Microcystis (Cyanobacteria) using PC‐IGS and 16S–23S ITS as markers: investigation of horizontal gene transfer
Authors: Piccin‐Santos Viviane , Brandão Marcelo Mendes , Bittencourt‐Oliveira Maria Do Carmo
Published: May 2014

Selection of genes that have not been horizontally transferred for prokaryote phylogenetic inferences is regarded as a challenging task. The markers internal transcribed spacer of ribosomal genes (16S–23S ITS) and phycocyanin intergenic spacer (PC‐IGS), based on the operons of ribosomal and phycocyanin genes respectively, are among the most used markers in cyanobacteria. The region of the ribosomal genes has been considered stable, whereas the phycocyanin operon may have undergone horizontal transfer. To investigate the occurrence of horizontal transfer of PC‐IGS, phylogenetic trees of Geitlerinema and Microcystis strains were generated using PC‐IGS and 16S–23S ITS and compared. Phylogenetic trees based on the two markers were mostly congruent for Geitlerinema and Microcystis, indicating a common evolutionary history among ribosomal and phycocyanin genes with no evidence for horizontal transfer of PC‐IGS. Thus, PC‐IGS is a suitable marker, along with 16S–23S ITS for phylogenetic studies of cyanobacteria.
Drug Prescription for Erectile Dysfunction Before and After Diagnosis of Localized Prostate Cancer
Authors: Plym Anna , Folkvaljon Yasin , Garmo Hans , Holmberg Lars , Johansson Eva , Fransson Per , Stattin Pär , Lambe Mats
Published: May 2014

Introduction

Despite the high prevalence of erectile dysfunction (ED) in men with prostate cancer, little is known about the use of ED drugs. Also, the possible influence of socioeconomic factors on ED drug use has not been studied previously.

Aim

The aim of this study was to examine determinants and patterns of ED drug use before and after diagnosis in men with localized prostate cancer.

Methods

Using a nationwide population-based cohort, 25,390 men with localized prostate cancer diagnosed between 2006 and 2009 and 126,944 control men were identified and followed for filled ED drug prescriptions over a 3-year period, ranging from 1 year before and up to 2 years after diagnosis.

Main Outcome Measures

The main outcome measure was the proportion of men with at least one filled ED drug prescription after diagnosis.

Results

The number of men using ED drugs increased markedly following diagnosis. Men who underwent radical prostatectomy had the strongest increase, with a cumulative proportion of 74% for at least one filled prescription within the first 2 years after diagnosis. The corresponding proportion was 33% in men treated with radiotherapy, 21% in men on active surveillance, 10% in men on watchful waiting, and 8% in control men. Among men who underwent prostatectomy, usage attenuated over time. Determinants of postdiagnostic use were young age at diagnosis, high income, high education, and a low- or intermediate-risk cancer.

Conclusion

Although drugs for ED are commonly prescribed after diagnosis, use among most men is transient and influenced by socioeconomic status. Posttreatment counseling and affordable ED drugs are likely to reduce treatment dropout and disparities in use and help improve sexual health and quality of life in men with prostate cancer.
Home range characteristics of a subordinate predator: selection for refugia or hunt opportunity?
Authors: Lendrum P. E. , Elbroch L. M. , Quigley H. , Thompson D. J. , Jimenez M. , Craighead D.
Published: May 2014

Cougars Puma concolor are described as ‘habitat generalists’, but little is known about which ecological factors drive their home range selection. For example, how do resource distributions and inter‐species competition with dominant competitors (i.e. wolves, Canis lupus) over such resources, influence the distributions of cougars on the landscape? We tracked cougars using Very High Frequency (VHF; 2001 to 2005) and Global Positioning System (GPS; 2006 to 2011) technology in the Southern Yellowstone Ecosystem (SYE) in northwestern Wyoming, USA. We tested whether data type (VHF vs. GPS), cougar sex, access to forests (refugia) or hunt opportunity explained the size of 50% and 95% kernel density estimator (KDE) home ranges. Second, we quantified attributes of cougar home ranges and tested whether they were different from attributes of the overall study area, to address the ecological question: Do cougars select home ranges based on the availability of refugia, hunt opportunity or some combination of the two? Cougar sex and data type proved significant predictors of home range size for both 95% and 50% KDEs, and the amount of forest partly explained the size of 50% KDEs. Cougar home ranges derived from VHF data were 1.4–1.9 times larger than home ranges derived from GPS data; however, home range attributes determined from VHF and GPS data were remarkably equivalent. Female cougars selected home ranges with higher hunt opportunity than males, supporting the assumption that females primarily select home ranges with suitable prey to sustain themselves and their young. All cougars selected home ranges further from known wolf packs, providing evidence for newly established competition between resident cougars and recolonizing wolves, but did not select home ranges with greater access to landscape refugia. Our results provided evidence that cougars in the SYE select home ranges that provide high hunting opportunity and a spatial buffer that mitigates potential conflicts with a dominant competitor.
Estimation of migration rates from marker‐based parentage analysis
Authors: Wang Jinliang
Published: May 2014

Coupled with rapid developments of efficient genetic markers, powerful population genetic methods were proposed to estimate migration rates (m) in natural populations in much broader spatial and temporal scales than the traditional mark‐release‐recapture (MRR) methods. Highly polymorphic (e.g. microsatellites) and genomic‐wide (e.g. SNPs) markers provide sufficient information to assign individuals to their populations or parents of origin and thereby to estimate directly m in a way similar to MRR. Such direct estimates of current migration rates are particularly useful in understanding the ecology and microevolution of wild populations and in managing the populations in the future. In this study, I proposed and implemented, in the software MigEst, a likelihood method to use marker‐based parentage assignments in jointly estimating m and candidate parent sampling proportions (x) in a subset of populations, investigated its power and accuracy using data simulated in various scenarios of population properties (e.g. the actual m, number, size and differentiation of populations) and sampling properties (e.g. the numbers of sampled parent candidates, offspring and markers), compared it with the population assignment approach implemented in the software BayesAss and demonstrated its usefulness by analysing a microsatellite data set from three natural populations of Brazilian bats. Simulations showed that MigEst provides unbiased and accurate estimates of m and performs better than BayesAss except when populations are highly differentiated with very small and ecologically insignificant migration rates. A valuable property of MigEst is that in the presence of unsampled populations, it gives good estimates of the rate of migration among sampled populations as well as of the rate of migration into each sampled population from the pooled unsampled populations.
Divergence with gene flow in a population of thermophilic bacteria: a potential role for spatially varying selection
Authors: Wall Christopher A. , Koniges Gregory J. , Miller Scott R.
Published: May 2014

A fundamental goal of evolutionary biology is to understand how ecological diversity arises and is maintained in natural populations. We have investigated the contributions of gene flow and divergent selection to the distribution of genetic variation in an ecologically differentiated population of a thermophilic cyanobacterium (Mastigocladus laminosus) found along the temperature gradient of a nitrogen‐limited stream in Yellowstone National Park. For most loci sampled, gene flow appears to be sufficient to prevent substantial genetic divergence. However, one locus (rfbC) exhibited a comparatively low migration rate as well as other signatures expected for a gene experiencing spatially varying selection, including an excess of common variants, an elevated level of polymorphism and extreme genetic differentiation along the gradient. rfbC is part of an expression island involved in the production of the polysaccharide component of the protective envelope of the heterocyst, the specialized nitrogen‐fixing cell of these bacteria. SNP genotyping in the vicinity of rfbC revealed a ~5‐kbp region including a gene content polymorphism that is tightly associated with environmental temperature and therefore likely contains the target of selection. Two genes have been deleted both in the predominant haplotype found in the downstream region of White Creek and in strains from other Yellowstone populations of M. laminosus, which may result in the production of heterocysts with different envelope properties. This study implicates spatially varying selection in the maintenance of variation related to thermal performance at White Creek despite on‐going or recent gene flow.