bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic testing preferences in families containing multiple individuals with epilepsy
Authors: Okeke Janice O. , Tangel Virginia E. , Sorge Shawn T. , Hesdorffer Dale C. , Winawer Melodie R. , Goldsmith Jeff , Phelan Jo C. , Chung Wendy K. , Shostak Sara , Ottman Ruth 
Published: September 2014

SummaryObjectiveTo examine genetic testing preferences in families containing multiple individuals with epilepsy.MethodsOne hundred forty‐three individuals with epilepsy and 165 biologic relatives without epilepsy from families containing multiple affected individuals were surveyed using a self‐administered questionnaire. Four genetic testing scenarios were presented, defined by penetrance (100% vs. 50%) and presence or absence of clinical utility. Potential predictors of genetic testing preferences were evaluated using generalized estimating equations with robust Poisson regression models. The influence of 21 potential testing motivations was also assessed.ResultsFor the scenario with 100% penetrance and clinical utility, 85% of individuals with epilepsy and 74% of unaffected relatives responded that they would definitely or probably want genetic testing. For the scenario with 100% penetrance but without clinical utility, the proportions who responded that they would want testing were significantly lower in both affected individuals (69%) and unaffected relatives (57%). Penetrance (100% vs. 50%) was not a significant predictor of genetic testing interest. The highest‐ranking motivations for genetic testing were the following: the possibility that the results could improve health or health care, the potential to know if epilepsy in the family is caused by a gene, and the possibility of changing behavior or lifestyle to prevent seizures.SignificanceInterest in epilepsy genetic testing may be high in affected and unaffected individuals in families containing multiple individuals with epilepsy, especially when testing has implications for improving clinical care.
Malassezia yeasts activate the NLRP3 inflammasome in antigen‐presenting cells via Syk‐kinase signalling
Authors: Kistowska Magdalena , Fenini Gabriele , Jankovic Dragana , Feldmeyer Laurence , Kerl Katrin , Bosshard Philipp , Contassot Emmanuel , French Lars E. 
Published: September 2014

AbstractAlthough being a normal part of the skin flora, yeasts of the genus Malassezia are associated with several common dermatologic conditions including pityriasis versicolour, seborrhoeic dermatitis (SD), folliculitis, atopic eczema/dermatitis (AE/AD) and dandruff. While Malassezia spp. are aetiological agents of pityriasis versicolour, a causal role of Malassezia spp. in AE/AD and SD remains to be established. Previous reports have shown that fungi such as Candida albicans and Aspergillus fumigatus are able to efficiently activate the NLRP3 inflammasome leading to robust secretion of the pro‐inflammatory cytokine IL‐1β. To date, innate immune responses to Malassezia spp. are not well characterized. Here, we show that different Malassezia species could induce NLRP3 inflammasome activation and subsequent IL‐1β secretion in human antigen‐presenting cells. In contrast, keratinocytes were not able to secrete IL‐1β when exposed to Malassezia spp. Moreover, we demonstrate that IL‐1β secretion in antigen‐presenting cells was dependent on Syk‐kinase signalling. Our results identify Malassezia spp. as potential strong inducers of pro‐inflammatory responses when taken up by antigen‐presenting cells and identify C‐type lectin receptors and the NLRP3 inflammasome as crucial actors in this process.
Polidocanol inhibits cowhage ‐ but not histamine‐induced itch in humans
Authors: Hawro Tomasz , Fluhr Joachim W. , Mengeaud Valérie , Redoulès Daniel , Church Martin K. , Maurer Marcus , Metz Martin 
Published: September 2014

AbstractPolidocanol is a local anaesthetic and antipruritic compound that is used in the treatment of itching skin conditions such as eczema. Its mechanisms of action are largely ill defined. This study has compared the antipruritic efficacy of topical polidocanol in histamine‐induced itch and a histamine‐independent, cowhage‐induced model of pruritus. Polidocanol (3%) or vehicle was applied topically under occlusion for 1 h to the forearms of 45 healthy volunteers before itch was provoked by rubbing in 40–45 spicules of cowhage or skin prick testing with 10 mg/ml histamine. Itch was recorded at 1‐min intervals for 30 min on a 100‐mm visual analogue scale. Polidocanol significantly reduced the area under the curve for cowhage‐induced itch by 58% (P < 0.05), but had no significant effect on histamine‐induced itch. This result underlines the importance of histamine‐independent itch models in the development of topical antipruritic agents.
Structure and mechanism of the primosome protein DnaT– functional structures for homotrimerization, dissociation of ssDNA from the PriB·ssDNA complex, and formation of the DnaT·ssDNA complex
Authors: Fujiyama Saki , Abe Yoshito , Tani Junya , Urabe Masashi , Sato Kenji , Aramaki Takahiko , Katayama Tsutomu , Ueda Tadashi 
Published: September 2014

In Escherichia coli, the primosome plays an essential role in replication restart after dissociation of replisomes at the damaged replication fork. As well as PriA and PriB, DnaT, an ssDNA‐binding protein, is a key member of the primosome. In this study, limited proteolysis indicated that E. coli DnaT was composed of two domains, consistent with the results of recent studies using Klebsiella pneumonia DnaT. We also found that a specific 24‐residue region (Phe42–Asp66) in the N‐terminal domain (1–88) was crucial for DnaT trimerization. Moreover, we determined the structure of the DnaT C‐terminal domain (89–179) by NMR spectroscopy. This domain included three α‐helices and a long flexible C‐terminal tail, similar to the C‐terminal subdomain of the AAA+ ATPase family. The neighboring histidines, His136 and His137, at a position corresponding to the AAA+ sensor II motif, were suggested to form an ssDNA‐binding site. Furthermore, we found that the acidic linker between the two domains had an activity for dissociating ssDNA from the PriB·ssDNA complexes in a manner supported by the conserved acidic residues Asp70 and Glu76. Thus, these findings provide a novel structural basis for understanding the mechanism of DnaT in exposure of ssDNA and reloading of the replicative helicase at the stalled replication fork.DatabaseThe coordinates used for the ensemble of NMR structures have been deposited in the Protein Data Bank under accession code 2ru8. The NMR data have been deposited in the BioMagResBank (www.bmrb.wisc.edu) under accession number 11549.Structured digital abstract

DnaT and DnaT bind by nuclear magnetic resonance (View interaction)

DnaT and PriB bind by isothermal titration calorimetry (View interaction)

DnaT and DnaT bind by molecular sieving (View interaction)
Lithium stimulates human bone marrow derived mesenchymal stem cell proliferation through GSK‐3β‐dependent β‐catenin/Wnt pathway activation
Authors: Zhu Zhenzhong , Yin Junhui , Guan Junjie , Hu Bin , Niu Xin , Jin Dongxu , Wang Yang , Zhang Changqing 
Published: September 2014

Mesenchymal stem cells (MSCs) are multipotent cells that have been widely used in cell based transplantation therapy. The use of MSCs requires in vitro expansion in order to fulfill their regenerative capacity. Therefore the proliferative ability of MSCs is one of the key factors which determine MSC therapeutic efficacy. In the present study, we showed for the first time that lithium, a well‐known antidepressant, reversibly promoted the proliferation of human bone marrow derived MSCs in vitro. MSCs treated with 5 mm lithium proliferated more rapidly than untreated cells without undergoing apoptosis. Lithium increased the proportion of cells in S phase as well as cyclin D1 expression. Mechanistic studies revealed that these effects were dependent upon the activation of the glycogen synthase kinase 3β (GSK‐3β) mediated canonical Wnt pathway. Lithium induced Ser9 phosphorylation, which results in the inhibition of GSK‐3β activity, β‐catenin accumulation and Wnt pathway activation. Utilizing a specific GSK‐3β inhibitor SB216763 or siRNA‐mediated inhibition of GSK‐3β produced effects similar to those induced by lithium. In contrast, either quercetin, an inhibitor of the β‐catenin/TCF pathway, or siRNA‐mediated knockdown of β‐catenin abolished the proliferative effect of lithium, suggesting that lithium stimulates MSC proliferation via the GSK‐3β‐dependent β‐catenin/Wnt pathway. Collectively, these studies elucidate a novel role of lithium, which may not only provide a simple and effective way to strengthen MSC transplantation therapy efficacy but also shed light on lithium's clinical application for the treatment of certain disorders resulting from β‐catenin/Wnt pathway suppression.
Cyanobacterial bloom termination: the disappearance of Planktothrix rubescens from Lake Bourget (France) after restoration
Authors: Jacquet Stéphan , Kerimoglu Onur , Rimet Frédéric , Paolini Gérard , Anneville Orlane 
Published: September 2014

Summary

Like many large freshwater ecosystems in Europe, Lake Bourget suffered from eutrophication during the second part of the 20th century and since the 1980s has been partially restored by reductions in nutrient loadings.

Here, we analyse a data set comprised of field measurements of physicochemical and biological variables in Lake Bourget covering the period from 2004 to 2011 and complement this data set with laboratory experiments, to gain an understanding of the changes in phytoplankton community structure during recent years and drivers of these changes.

Between 1995 and 2008, Lake Bourget was characterised by the proliferation of the red‐coloured filamentous and toxic cyanobacterium Planktothrix rubescens, comprising 34.1–52.6% of the total phytoplanktonic biomass between 2004 and 2008.

In 2009, although the contribution of P. rubescens to the total biomass was still considerable (25.3%), it was significantly lower (P < 0.05) compared with previous years. The cyanobacterium disappeared completely during the autumn to winter transition of 2009/2010 and has not been recorded since this time.

Concomitantly, total phytoplanktonic biomass declined sharply and a new phytoplanktonic community occurred consisting predominantly of mixotrophic genera, such as Dinobryon spp., Rhodomonas, Cryptomonas and a variety of different diatoms such as Stephanodiscus, Cyclotella and Fragilaria.

Our findings suggest declines in phosphorus concentration as a key variable in bloom termination, although a number of other factors could also be important, such as temperature‐dependent water column mixing, light availability, zooplankton grazing and seasonal cyanobacterial inoculums.
Breeding in the stable boreal landscape: lake habitat variability drives brood production in the teal (Anas crecca)
Authors: Holopainen Sari , Nummi Petri , Pöysä Hannu 
Published: September 2014

Summary

Boreal forest lakes are normally considered stable environments, but from a duck's point of view, both resource abundance and habitat quality in the lakes may differ from 1 year to another. Duck species differ in their flexibility to respond to variation in environmental factors, such as habitat quality, habitat variability and weather. Anas crecca, the common teal, has been suggested to be a species that can readily colonise newly formed habitat.

We studied the effect of habitat quality (invertebrate food resources, amount of spring flood, beaver flood abundance, predation pressure), weather (temperature, precipitation, timing of ice break‐up) and pair abundance on breeding success of teal at the landscape scale in Southern Finland. We used 20 years of data (1989–2008) from a study area consisting of 50 lakes. This is typical boreal breeding area for the teal, whose population size is markedly variable. We express breeding success as number of broods in two different age classes.

The number of broods in both age classes was explained well by habitat quality, but different variables seem to operate during different phases of the breeding season. Increases in abundance of breeding pairs and of food led to increased production of younger broods. Habitat factors including food and flood abundance were the most important predictors for older broods, which are the more influential in terms of recruitment. These factors manifested in an age‐specific manner, highlighting the importance of comprehensive breeding time surveys of boreal breeding ducks to understand variation in their recruitment.

Our research underlines the importance of high‐quality habitats for breeding teal populations in the boreal forest landscape. The existence of these habitats depends substantially on human actions, such as managing beaver populations and preserving seasonal pond habitats.
Mortality, movement and behaviour of native mussels during a planned water‐level drawdown in the Upper Mississippi River
Authors: Newton Teresa J. , Zigler Steve J. , Gray Brian R. 
Published: September 2014

Summary

Managers in the Upper Mississippi River (UMR) are using reductions in the River's water levels during summer to mimic historical water regimes and rehabilitate habitats for vegetation and other species. Concerns for the unintended effects of these actions on mussel populations threatened to halt these projects.

Our objective was to characterise the survival and movement of two mussel species in the UMR associated with a water level drawdown. During 2009 (no drawdown) and 2010 (0.3 m summer drawdown), we glued passive integrated transponder tags to 10 Amblema plicata and 10 Lampsilis cardium at each of 11 sites. Five sites were in shallow areas expected to be minimally affected by the drawdown (reference sites), and six sites were in shallow areas expected to be directly affected by the drawdown (treatment sites). About equal numbers of sites within both the reference and treatment areas had low and high slopes. Tagged mussels were randomly allocated across sites (within years).

Recovery of tagged mussels was >88% in 2009 and 2010. Mortality was similar and low (mean, c. 5% in both species) among reference sites but was variable and relatively high (means, c. 27% in L. cardium and c. 52% in A. plicata) among treatment sites; variation in mortality among treatment sites appeared related to slope.

The study found evidence of drawdown associations with net horizontal movements in A. plicata but not L. cardium. Weekly horizontal movements in both species were significantly correlated with changes in water elevation. We observed significant slope associations related to the drawdown for mortality and net horizontal movement in A. plicata.

There were strong species‐specific differences in the effects of the drawdown on mortality, vertical movement and horizontal movement. These results suggest that A. plicata responded to the drawdown by vertical movement into the substratum, whereas L. cardium responded by horizontal movement to deeper water. No directionality of movement was observed in either species.

Collectively, these data suggest that drawdowns can influence the mortality, movement and behaviour of mussels in the UMR. However, more information on spatial and temporal distributions of mussels is needed to better understand the magnitude of these effects. Results from this study are being used by resource managers to better evaluate the effects of this management tool on native mussel assemblages.
Effects of nutrients and warming on Planktothrix dynamics and diversity: a palaeolimnological view based on sedimentary DNA and RNA
Authors: Savichtcheva Olga , Debroas Didier , Perga Marie Elodie , Arnaud Fabien , Villar Clément , Lyautey Emilie , Kirkham Amy , Chardon Cécile , Alric Benjamin , Domaizon Isabelle 
Published: September 2014

Summary

Decennial changes in Planktothrix rubescens diversity and dynamics were reconstructed by applying molecular tools to analyse DNA and RNA extracted from lake sediments. The sediments studied were sampled from a deep peri‐alpine lake that has experienced both dramatic shifts in trophic conditions and large‐scale climatic changes. Palaeolimnological proxies were combined with statistical modelling to investigate the relative influence of phosphorus concentrations and temperature changes on the extent of Planktothrix blooms over the last century.

Phylogenetic analysis revealed that the overall composition of the cyanobacterial community changed over the transition from oligotrophic to eutrophic conditions. When the relative abundance of Planktothrix decreased in the 1970s, concomitant with eutrophication, total cyanobacterial abundance remained high and more Anabaena and Microcystis sequences were detected. In spite of such drastic environmental changes, the lake provided a constant niche for one particular Planktothrix species, which was consistently present from the 1920s to the present day.

Phosphorus concentration was found to be the dominant driver of the relative abundance of P. rubescens, with the highest abundances observed during mesotrophic conditions. The relative role of climate was nutrient‐dependent, with warmer springs having a positive effect on P. rubescens abundance only during mesotrophic periods.

Overall, this study confirms that analysis of genetic signatures preserved in sediment archives allows assessment of key palaeoenvironmental indicator species that have no diagnostic microscopic cellular features in the sediment record. In the case of cyanobacteria, palaeogenetics offer unique opportunities to anticipate how future climate change might affect the response of P. rubescens to phosphorus concentration.
Reduced investment in sex as a cost of inducible defence inBrachionus calyciflorus(Rotifera)
Authors: Yin Xu Wang , Zhou Yan Chun , Li Xiao Chun , Li Wen Xiang 
Published: September 2014

SummaryInducible defences reduce the probability of prey being killed by their predators. However, these defences are often accompanied by costs. Most studies associated with aquatic communities have focused on the effects of inducible defences on the growth and reproduction of prey species, while their effects on sex investment remain unclear.Brachionus calyciflorusis a common freshwater rotifer that develops a defensive morphology in response to the kairomones released by the predatory rotiferAsplanchna. Some studies have reported that no detectable cost, such as decreased reproductive output, is associated with the spines inB. calyciflorus. Thus, we studied the sex investment (i.e. production of mictic offspring and resting eggs) ofB. calycifloruspopulations at threeAsplanchnakairomone concentrations (0, 10, and 100 Asplanchna L−1) and two food levels (1 and 12 mg C L−1) to evaluate the sex cost of inducible defences. We also evaluated the crowding threshold required to trigger sex investment (i.e. lowest population density at which mictic female is produced) inB. calyciflorusunder different kairomone and food treatments.Results showed that (i) theB. calycifloruspopulation exposed to kairomones produced offspring with elongated posterolateral spines; (ii) the production of mictic offspring and resting eggs decreased in theB. calycifloruspopulation exposed to kairomones, suggesting an investment trade‐off exists between inducible defence and sex investment; (iii) the decrease in sex investment was higher at the high kairomone concentration than at the low kairomone concentration; (iv) the decrease of sex investment was higher at the low food level than at the high food level; and (v) the crowding threshold of theB. calycifloruspopulation increased upon exposure to kairomones.The results of this study suggest that the decreased sex investment in defendedB. calyciflorusis a form of defence cost. Our findings add to our understanding of the effect of predation on the ecology and evolution of phenotypic plasticity in rotifers.
Normal stress‐induced permeability hysteresis of a fracture in a granite cylinder
Authors: Selvadurai A. P. S. 
Published: September 2014

AbstractThe paper examines the influence of axial stress‐induced closure of a fracture on its permeability. The experiments were conducted on a cylinder of Barre Granite measuring 457 mm in diameter and 510 mm in height, containing a central cylindrical cavity of diameter 75 mm. Radial flow hydraulic pulse tests were conducted in a previous research investigation (Selvadurai et al., PAGEOPH, 2005) to determine the permeability characteristics of the intact granite. In the continuation of the research, a fracture was introduced in the cylinder with its nominal plane normal to the axis of the cylinder. Axial compressive stress was applied normal to the plane of the fracture. An increase in the compressive normal stress acting on the fracture caused a reduction in the aperture of the fracture, which resulted in the reduction in its permeability. Steady state radial flow tests were conducted on the fractured axially stressed sample to determine the variation of fracture permeability with axial normal stress. The analytical developments also take into account flow through the matrix region as the normal stress increases. The results of the experimental investigations indicate that the complete stress relief of a fracture previously subjected to a normal stress of 7.5 MPa can result in a permeability increase of approximately three orders of magnitude. These findings are relevant to shallow depth geotechnical construction activities where enhanced fluid flow can be activated by stress relief. As the fracture aperture closes with high normal stress, the flow through the matrix can be appreciable and if this factor is not taken into consideration the interpretation of fracture permeability can be open to error. This factor can be of interest to the interpretation of permeability of fractures in deep crustal settings where the stresses acting normal to the fracture surface can inhibit flow in the fracture.
Expression of haem oxygenase‐1 correlates with tumour aggressiveness and BRAFV600E expression in thyroid cancer
Authors: Wang Tao‐Yeuan , Liu Chien‐Liang , Chen Ming‐Jen , Lee Jie‐Jen , Pun Pou Chu , Cheng Shih‐Ping 
Published: September 2014

AimsHaem oxygenase‐1 (HO‐1) is an inducible enzyme that participates in haem degradation. Recent studies have indicated that HO‐1 activation may play a role in tumour development and progression. The aim of this study was to evaluate the expression of HO‐1 in thyroid cancer and its clinicopathological significance.Methods and resultsWe observed up‐regulation of HO‐1 in papillary thyroid tumours in comparison with normal thyroid tissue. Immunohistochemical analysis revealed that 48% of papillary cancers and 36% of follicular cancers, but none of normal thyroid tissues, were positive for HO‐1 expression. Among 129 differentiated thyroid cancers, HO‐1 expression was associated with patient age (P = 0.001), TNM stage (P = 0.001), and Mayo Clinic metastasis, patient age, completeness of resection, local invasion and tumour size score (P = 0.001). BRAFV600E expression was evaluated immunohistochemically and validated by Sanger sequencing. There was a strong association between HO‐1 and BRAFV600E expression in papillary cancers (P = 0.002).ConclusionsOverexpression of HO‐1 in a subset of thyroid cancers is associated with tumour aggressiveness and BRAFV600E expression. HO‐1 might have a potential role in prognosis and targeted treatment in patients with thyroid cancer.