bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of magical thinking in forecasting the future
Authors: Stavrova Olga , Meckel Andrea
Published: February 2016

This article explores the role of magical thinking in the subjective probabilities of future chance events. In five experiments, we show that individuals tend to predict a more lucky future (reflected in probability judgements of lucky and unfortunate chance events) for someone who happened to purchase a product associated with a highly moral person than for someone who unknowingly purchased a product associated with a highly immoral person. In the former case, positive events were considered more likely than negative events, whereas in the latter case, the difference in the likelihood judgement of positive and negative events disappeared or even reversed. Our results indicate that this effect is unlikely to be driven by participants’ immanent justice beliefs, the availability heuristic, or experimenter demand. Finally, we show that individuals rely more heavily on magical thinking when their need for control is threatened, thus suggesting that lack of control represents a factor in driving magical thinking in making predictions about the future.
Berberine improves mesenteric artery insulin sensitivity through up‐regulating insulin receptor‐mediated signalling in diabetic rats
Authors: Geng Feng‐Hao , Li Guo‐Hua , Zhang Xing , Zhang Peng , Dong Ming‐Qing , Zhao Zhi‐Jing , Zhang Yuan , Dong Ling , Gao Feng
Published: February 2016

Background and Purpose

Berberine, a small molecule derived from Coptidis rhizome, has been found to be potent at lowering blood glucose and regulating lipid metabolism. Recent clinical studies have shown that berberine reduces blood pressure and increases systemic insulin sensitivity in patients with metabolic syndrome; however, the underlying mechanism is still unclear. Here, we investigated the mechanism by which berberine improves vascular insulin sensitivity in diabetic rats.

Experimental Approach

Diabetes was induced in male Sprague–Dawley rats by feeding a high‐fat diet and administration of a low dose of streptozotocin. These diabetic rats were treated with berberine (200 mg·kg−1·day−1, gavage) for 4 weeks. Vascular dilation was determined in isolated mesenteric artery rings. Effects of berberine on insulin signalling were also studied in human artery endothelial cells cultured in high glucose (25 mmol·L−1) and palmitate (500 μmol·L−1).

Key Results

Berberine treatment for 4 weeks significantly restored the impaired ACh‐ and insulin‐induced vasodilatation of mesenteric arteries from diabetic rats. In isolated mesenteric artery rings, berberine (2.5–10 μmol·L−1) elicited dose‐dependent vasodilatation and significantly enhanced insulin‐induced vasodilatation. Mechanistically, berberine up‐regulated phosphorylation of the insulin receptor and its downstream signalling molecules AMPK, Akt and eNOS, and increased cell viability and autophagy in cultured endothelial cells. Moreover, down‐regulating insulin receptors with specific siRNA significantly attenuated berberine‐induced phosphorylation of AMPK.

Conclusions and Implications

Berberine improves diabetic vascular insulin sensitivity and mesenteric vasodilatation by up‐regulating insulin receptor‐mediated signalling in diabetic rats. These findings suggest berberine has potential as a preventive or adjunctive treatment of diabetic vascular complications.

Linked Articles

This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23.
Endothelin‐1 shifts the mediator of bradykinin‐induced relaxation from NO to H2O2 in resistance arteries from patients with cardiovascular disease
Authors: Leurgans Thomas M , Bloksgaard Maria , Brewer Jonathan R , Bagatolli Luis A , Fredgart Maise H , Rosenstand Kristoffer , Hansen Maria L , Rasmussen Lars M , Irmukhamedov Akhmadjon , De Mey Jo GR
Published: February 2016

Background and Purpose

We tested the hypothesis that in resistance arteries from cardiovascular disease (CVD) patients, effects of an endothelium‐dependent vasodilator depend on the contractile stimulus.

Experimental Approach

Arteries dissected from parietal pericardium of cardiothoracic surgery patients were studied by myography and imaging techniques. Segments were sub‐maximally contracted by K+, the TxA2 analogue U46619 or endothelin‐1 (ET‐1).

Key Results

Relaxing effects of Na‐nitroprusside were comparable, but those of bradykinin (BK) were bigger in the presence of ET‐1 compared with K+ or U46619. BK‐induced relaxation was (i) abolished by L‐NAME in K+‐contracted arteries, (ii) partly inhibited by L‐NAME in the presence of U46619 and (iii) not altered by indomethacin, L‐NAME plus inhibitors of small and intermediate conductance calcium‐activated K+ channels, but attenuated by catalase, in ET‐1‐contracted arteries. This catalase‐sensitive relaxation was unaffected by inhibitors of NADPH oxidases or allopurinol. Exogenous H2O2 caused a larger relaxation of ET‐1‐induced contractions than those evoked by K+ or U46619 in the presence of inhibitors of other endothelium‐derived relaxing factors. Catalase‐sensitive staining of cellular ROS with CellROX Deep Red was significantly increased in the presence of both 1 μM BK and 2 nM ET‐1 but not either peptide alone.

Conclusions and Implications

In resistance arteries from patients with CVD, exogenous ET‐1 shifts the mediator of relaxing responses to the endothelium‐dependent vasodilator BK from NO to H2O2 and neither NADPH oxidases, xanthine oxidase nor NOS appear to be involved in this effect. This might have consequences for endothelial dysfunction in conditions where intra‐arterial levels of ET‐1 are enhanced.
Antinociceptive effects of sinomenine in a rat model of postoperative pain
Authors: Zhu Qing , Sun Yuehua , Mao Lina , Liu Chengpeng , Jiang Bo , Zhang Wei , Li Jun‐Xu
Published: February 2016

Background and Purpose

This study examined the antinociceptive effects of sinomenine in a rat model of postoperative pain.

Experimental Approach

Male and female rats were subjected to a surgical incision in the right hind paw, and the von Frey filament test was used to measure mechanical hypersensitivity after drug or vehicle treatment (p.o. or i.p.). Rats were treated daily with sinomenine before or after the surgery and the AUCs of the antinociceptive effects measured during a 4 h period were calculated to determine the ED50 values of sinomenine. The anti‐hyperalgesic effects of different doses of a combination of sinomenine and acetaminophen (paracetamol) were assessed in another group of rats. Dose combinations were determined by using a fixed ratio dose‐addition analysis method.

Key Results

Sinomenine (5–80 mg·kg−1) produced dose‐dependent antinociceptive effects in rats that had been subjected to surgery and this effect lasted for 4 h. The potency of sinomenine, given i.p. or p.o., did not differ between male and female rats. However, sinomenine was fourfold more potent when given i.p. than p.o. The GABAA receptor antagonist bicuculline blocked the antinociceptive effects of sinomenine. The antinociceptive effect of a daily treatment with sinomenine remained stable throughout the course of postoperative pain. Pretreatment with sinomenine did not alter the mechanical hypersensitivity post‐surgery. The combination of sinomenine with acetaminophen produced an infra‐additive interaction.

Conclusions and Implications

Sinomenine demonstrated significant antinociceptive activity against postoperative pain and may be a useful novel pharmacotherapy for the management of postoperative pain.
Lenalidomide and low‐dose dexamethasone in Japanese patients with newly diagnosed multiple myeloma: A phase II study
Authors: Suzuki Kenshi , Shinagawa Atsushi , Uchida Toshiki , Taniwaki Masafumi , Hirata Hirokazu , Ishizawa Kenichi , Matsue Kosei , Ogawa Yoshiaki , Shimizu Takayuki , Otsuka Maki , Matsumoto Morio , Iida Shinsuke , Terui Yasuhito , Matsumura Itaru , Ikeda Takashi , Takezako Naoki , Ogaki Yumi , Midorikawa Shuichi , Houck Vanessa , Ervin‐Haynes Annette , Chou Takaaki
Published: February 2016

In the FIRST trial (MM‐020), lenalidomide plus low‐dose dexamethasone (Rd) reduced the risk of disease progression or death compared with combination melphalan–prednisone–thalidomide. As the FIRST trial did not include any Japanese patients, the efficacy and safety of continuous treatment with Rd was evaluated in 26 Japanese patients with newly diagnosed multiple myeloma (NDMM) in a single‐arm, multicenter, open‐label phase II trial (MM‐025). Patients received lenalidomide on days 1–21 of each 28‐day cycle, with a starting dose of 25 mg/day (dose adjusted for renal impairment), and 40 mg/day dexamethasone (dose adjusted for age) on days 1, 8, 15 and 22 of each 28‐day cycle until disease progression or discontinuation for any reason. In the efficacy evaluable population, overall response rate was 87.5%, including 29.2% of patients who achieved a complete response/very good partial response. Median durations of response, progression‐free survival and overall survival have not been reached. The most common grade 3–4 adverse events were neutropenia (23%) and anemia (19%). The efficacy and safety of Rd were consistent with data from larger studies, including the FIRST trial, thereby supporting the use of Rd continuous in Japanese patients with NDMM who are ineligible for stem cell transplantation.
No widening socioeconomic gap within a general decline in Swedish breastfeeding
Authors: Magnusson M. , Lagerberg D. , Wallby T.
Published: February 2016

Aim

To study potential socioeconomic differences within the general decline in breastfeeding over time.

Methods

Data was collected for 51 415 infants born 2004–2010 from the databases of statistics of the Preventive Child Health Care Services in Uppsala and Orebro counties in Sweden and socioeconomic indicators from Swedish national registers. Breastfeeding data (breastfed/not breastfed) from 1 week, 4 months and 6 months of age were used as the main outcome variables. Educational level of the mother was defined as the highest level on a three‐grade scale, low, medium and high. Family type was defined as whether the mother was single or married/cohabiting. Family disposable income was divided into quartiles where quartile 1 included the 25% children in families with the lowest incomes. Analyses were conducted by logistic regression models using the methodology of generalized estimating equations (GEE). An exchangeable correlation structure was used to control for the dependence among infants with the same mother.

Results

Breastfeeding rate in Sweden has declined gradually since the late 1990s. The results indicated that overall breastfeeding rates over the study period were influenced by socioeconomic status in a gradient manner but no widening socioeconomic gap was detected. Rather the interaction analyses showed a narrowing socioeconomic gap over the study period between high and low educational level and single versus cohabiting mothers at 4 months. The narrowing socioeconomic gap between the educational level categories was also detectable at 6 months.

Conclusion

No increase in socioeconomic gap was detected within the general decline in Swedish breastfeeding. However, there are reasons to maintain and strengthen the overall breastfeeding supportive measures including extended support for vulnerable groups.
Osteogain improves osteoblast adhesion, proliferation and differentiation on a bovine‐derived natural bone mineral
Authors: Miron Richard J. , Fujioka‐Kobayashi Masako , Zhang Yufeng , Caballé‐Serrano Jordi , Shirakata Yoshinori , Bosshardt Dieter D. , Buser Daniel , Sculean Anton
Published: February 2016

Background

The use of enamel matrix derivative (EMD) has been shown to facilitate periodontal regeneration by histologically resulting in formation of cementum, periodontal ligament and bone. Recently, a new liquid carrier system for EMD has been introduced with better physicochemical properties specifically designed for bone graft mixing (Osteogain). The aim of this study was to investigate the combination of Osteogain with a bovine‐derived natural bone mineral (NBM) on osteoblast migration, adhesion, proliferation and differentiation.

Materials and Methods

Undifferentiated mouse ST2 stromal bone marrow cells were seeded onto 1)NBM particles alone or 2)NBM + Osteogain. Samples were compared for cell migration at 8 h, cell adhesion at 4 h, cell proliferation at 1, 3 and 5 days and real‐time PCR at 3 and 14 days for genes encoding runt‐related transcription factor 2 (Runx2), collagen1alpha2 (COL1a2), alkaline phosphatase (ALP) and osteocalcin (OCN). Furthermore, alizarin red staining was utilized to investigate the mineralization at 14 days.

Results

Osteogain significantly upregulated cell adhesion over twofold onto NBM particles and promoted cell proliferation at 3 and 5 days after seeding. Furthermore, the combination of NBM with Osteogain significantly upregulated genes encoding Runx2, ALP, COL1a2 and OCN (from 1.5‐ to 3‐fold) and increased alizarin red staining over 3 fold at 14 days when compared to NBM particles alone.

Conclusion

Pre‐coating Osteogain onto NBM bone grafting particles significantly increased cell adhesion, proliferation and differentiation of osteoblasts in vitro. Future animal studies are now necessary to further investigate the regenerative potential of Osteogain in combination with a bone grafting material prior to clinical use for bone regeneration.
Medieval Arab Contributions to Optics
Authors: Khan Sameen Ahmed
Published: February 2016

The year 2015 was the United Nations’ International Year of Light and Light‐based Technologies. The year long activities created a forum for scientists and engineers and all others inspired by light, to interact with each other and with the public so as to learn more about the nature of light and its many applications. It was also a time to promote and celebrate the Medieval Arab contributions to optics. The year 2015 marked the 1000th anniversary of the seven volume encyclopedia on optics written by the great Arab scientist, Ibn al‐Haytham. Here, we present the Medieval Arab achievements in optical sciences and its impact on the European renaissance.
Effect of Cry1F maize on the behavior of susceptible and resistant Spodoptera frugiperda and Ostrinia nubilalis
Authors: Vélez Ana María , Alves Analiza P. , Blankenship Erin E. , Siegfried Blair D.
Published: February 2016

Understanding the behavior of pests targeted with Bacillus thuringiensis Berliner (Bt) crops is important to define resistance management strategies. Particularly the study of larval movement between plants is important to determine the feasibility of refuge configurations. Exposure to Bt maize, Zea mays L. (Poaceae), has been suggested to increase larval movement in lepidopteran species but few studies have examined the potential for resistance to interact with behavioral responses to Bt toxins. Choice and no‐choice experiments were conducted with Spodoptera frugiperda (JE Smith) (Lepidoptera: Noctuidae) and Ostrinia nubilalis (Hübner) (Lepidoptera: Crambidae) to determine whether Cry1F resistance influences neonate movement. Leaf discs of Cry1F maize and the corresponding isoline were used to characterize behavioral responses. In both experiments, the location (on or off of plant tissues) and mortality of susceptible and Cry1F resistant neonates was recorded for 5 days, but the analysis of larvae location was performed until 7 h. Our results indicated no strong difference between resistant and susceptible phenotypes in S. frugiperda and O. nubilalis, although a small percentage of susceptible neonates in both species abandoned maize tissue expressing Cry1F. However, significant behavioral differences were observed between species. Ostrinia nubilalis exhibited increased movement between leaf discs, whereas S. frugiperda selected plant tissue within the first 30 min and remained on the chosen plant regardless of the presence of Cry1F. Spodoptera frugiperda reduced larval movement may have implications to refuge configuration. This study represents the first step toward understanding the effects of Cry1F resistance on Lepidoptera larval behavior. Information regarding behavioral differences between species could aid in developing better and more flexible resistance management strategies.
Zinc finger transcription factor Casz1 expression is regulated by homeodomain transcription factor Prrxl1 in embryonic spinal dorsal horn late‐born excitatory interneurons
Authors: Monteiro César B. , Midão Luís , Rebelo Sandra , Reguenga Carlos , Lima Deolinda , Monteiro Filipe A.
Published: February 2016

The transcription factor Casz1 is required for proper assembly of vertebrate vasculature and heart morphogenesis as well as for temporal control of Drosophila neuroblasts and mouse retina progenitors in the generation of different cell types. Although Casz1 function in the mammalian nervous system remains largely unexplored, Casz1 is expressed in several regions of this system. Here we provide a detailed spatiotemporal characterization of Casz1 expression along mouse dorsal root ganglion (DRG) and dorsal spinal cord development by immunochemistry. In the DRG, Casz1 is broadly expressed in sensory neurons since they are born until perinatal age. In the dorsal spinal cord, Casz1 displays a more dynamic pattern being first expressed in dorsal interneuron 1 (dI1) progenitors and their derived neurons and then in a large subset of embryonic dorsal late‐born excitatory (dILB) neurons that narrows gradually to become restricted perinatally to the inner portion. Strikingly, expression analyses using Prrxl1‐knockout mice revealed that Prrxl1, a key transcription factor in the differentiation of dILB neurons, is a positive regulator of Casz1 expression in the embryonic dorsal spinal cord but not in the DRG. By performing chromatin immunoprecipitation in the dorsal spinal cord, we identified two Prrxl1‐bound regions within Casz1 introns, suggesting that Prrxl1 directly regulates Casz1 transcription. Our work reveals that Casz1 lies downstream of Prrxl1 in the differentiation pathway of a large subset of dILB neurons and provides a framework for further studies of Casz1 in assembly of the DRG–spinal circuit.
Lysophosphatidic acid regulates adhesion molecules and enhances migration of human oral keratinocytes
Authors: Thorlakson Hong H. , Schreurs Olav , Schenck Karl , Blix Inger J. S.
Published: February 2016

Oral keratinocytes are connected via cell‐to‐cell adhesions to protect underlying tissues from physical and bacterial damage. Lysophosphatidic acids (LPAs) are a family of phospholipid mediators that have the ability to regulate gene expression, cytoskeletal rearrangement, and cytokine/chemokine secretion, which mediate proliferation, migration, and differentiation. Several forms of LPA are found in saliva and gingival crevicular fluid, but it is unknown how they affect human oral keratinocytes (HOK). The aim of the present study was therefore to examine how different LPA forms affect the expression of adhesion molecules and the migration and proliferation of HOK. Keratinocytes were isolated from gingival biopsies obtained from healthy donors and challenged with different forms of LPA. Quantitative real‐time RT‐PCR, immunocytochemistry, and flow cytometry were used to analyze the expression of adhesion molecules. Migration and proliferation assays were performed. Lysophosphatidic acids strongly promoted expression of E‐cadherin and occludin mRNAs and translocation of E‐cadherin protein from the cytoplasm to the membrane. Occludin and claudin‐1 proteins were up‐regulated by LPA. Migration of HOK in culture was increased, but proliferation was reduced, by the addition of LPA. This indicates that LPA can have a role in the regulation of the oral epithelial barrier by increasing the expression of adhesion molecules of HOK, by promotion of migration and by inhibition of proliferation.
De novo GABRA1 mutations in Ohtahara and West syndromes
Authors: Kodera Hirofumi , Ohba Chihiro , Kato Mitsuhiro , Maeda Toshiyuki , Araki Kaoru , Tajima Daisuke , Matsuo Muneaki , Hino‐Fukuyo Naomi , Kohashi Kosuke , Ishiyama Akihiko , Takeshita Saoko , Motoi Hirotaka , Kitamura Taro , Kikuchi Atsuo , Tsurusaki Yoshinori , Nakashima Mitsuko , Miyake Noriko , Sasaki Masayuki , Kure Shigeo , Haginoya Kazuhiro , Saitsu Hirotomo , Matsumoto Naomichi
Published: February 2016

Objective

GABRA1 mutations have been identified in patients with familial juvenile myoclonic epilepsy, sporadic childhood absence epilepsy, and idiopathic familial generalized epilepsy. In addition, de novo GABRA1 mutations were recently reported in a patient with infantile spasms and four patients with Dravet syndrome. Those reports suggest that GABRA1 mutations are associated with infantile epilepsy including early onset epileptic encephalopathies. In this study, we searched for GABRA1 mutations in patients with infantile epilepsy to investigate the phenotypic spectrum of GABRA1 mutations.

Methods

In total, 526 and 145 patients with infantile epilepsy were analyzed by whole‐exome sequencing and GABRA1‐targeted resequencing, respectively.

Results

We identified five de novo missense GABRA1 mutations in six unrelated patients. A p.R112Q mutation in the long extracellular N‐terminus was identified in a patient with infantile epilepsy; p.P260L, p.M263T, and p.M263I in transmembrane spanning domain 1 (TM1) were identified in three unrelated patients with West syndrome and a patient with Ohtahara syndrome, respectively; and p.V287L in TM2 was identified in a patient with unclassified early onset epileptic encephalopathy. Four of these mutations have not been observed previously.

Significance

Our study suggests that de novo GABRA1 mutations can cause early onset epileptic encephalopathies, including Ohtahara syndrome and West syndrome.
Serotonin signalling is crucial in the induction of PUVA‐induced systemic suppression of delayed‐type hypersensitivity but not local apoptosis or inflammation of the skin
Authors: Wolf Peter , Byrne Scott N. , Limon‐Flores Alberto Y. , Hoefler Gerald , Ullrich Stephen E.
Published: February 2016

Psoralen and UVA (PUVA) has immunosuppressive and proapoptotic effects, which are thought to be responsible alone or in combination for its therapeutic efficacy. However, the molecular mechanism by which PUVA mediates its effects is not well understood. Activation of the serotonin (5‐hydroxytryptamine, 5‐HT) pathway has been suggested to be involved in the modulation of T‐cell responses and found to mediate UVB‐induced immune suppression. In particular, the activation of the 5‐HT2A receptor has been proposed as one mechanism responsible for UV‐induced immune suppression. We therefore hypothesized that 5‐HT may play a role in PUVA‐induced effects. The model of systemic suppression of delayed‐type hypersensitivity (DTH) to Candida albicans was used to study immune function after exposure of C3H and KITW‐Sh/W‐Sh mice to a minimal inflammatory dose of topical PUVA. The intra‐peritoneal injection of the 5‐HT2 receptor antagonist ketanserin or cyproheptadine or an anti‐5‐HT antibody immediately before PUVA exposure entirely abrogated suppression of DTH but had no significant effect on inflammation, as measured by swelling and cellular infiltration of the skin, and apoptosis as determined by the number of sunburn cells in C3H mice. Importantly, the systemic injection of 5‐HT recapitulated PUVA immune suppression of DTH but did not induce inflammation or apoptosis in the skin. KITW‐Sh/W‐Sh mice (exhibiting myelopoietic abnormalities, including lack of 5‐HT‐containing mast cells) were resistant to PUVA‐induced suppression of DTH but not local skin swelling. Thus, this points towards a crucial role of 5‐HT signalling in PUVA‐induced immune suppression but not inflammation or apoptosis in situ in the skin.
γ‐Crystallins of the chicken lens: remnants of an ancient vertebrate gene family in birds
Authors: Chen Yingwei , Sagar Vatsala , Len Hoay‐Shuen , Peterson Katherine , Fan Jianguo , Mishra Sanghamitra , McMurtry John , Wilmarth Phillip A. , David Larry L. , Wistow Graeme
Published: February 2016

γ‐Crystallins, abundant proteins of vertebrate lenses, were thought to be absent from birds. However, bird genomes contain well‐conserved genes for γS‐ and γN‐crystallins. Although expressed sequence tag analysis of chicken eye found no transcripts for these genes, RT‐PCR detected spliced transcripts for both genes in chicken lens, with lower levels in cornea and retina/retinal pigment epithelium. The level of mRNA for γS in chicken lens was relatively very low even though the chicken crygs gene promoter had lens‐preferred activity similar to that of mouse. Chicken γS was detected by a peptide antibody in lens, but not in other ocular tissues. Low levels of γS and γN proteins were detected in chicken lens by shotgun mass spectroscopy. Water‐soluble and water‐insoluble lens fractions were analyzed and 1934 proteins (< 1% false discovery rate) were detected, increasing the known chicken lens proteome 30‐fold. Although chicken γS is well conserved in protein sequence, it has one notable difference in leucine 16, replacing a surface glutamine conserved in other γ‐crystallins, possibly affecting solubility. However, L16 and engineered Q16 versions were both highly soluble and had indistinguishable circular dichroism, tryptophan fluorescence and heat stability (melting temperature Tm ~ 65 °C) profiles. L16 has been present in birds for over 100 million years and may have been adopted for a specific protein interaction in the bird lens. However, evolution has clearly reduced or eliminated expression of ancestral γ‐crystallins in bird lenses. The conservation of genes for γS‐ and γN‐crystallins suggests they may have been preserved for reasons unrelated to the bulk properties of the lens.
Transcriptional signature induced by a metastasis‐promoting c‐Src mutant in a human breast cell line
Authors: Broecker Felix , Hardt Christopher , Herwig Ralf , Timmermann Bernd , Kerick Martin , Wunderlich Andrea , Schweiger Michal R. , Borsig Lubor , Heikenwalder Mathias , Lehrach Hans , Moelling Karin
Published: February 2016

Deletions at the C‐terminus of the proto‐oncogene protein c‐Src kinase are found in the viral oncogene protein v‐Src as well as in some advanced human colon cancers. They are associated with increased kinase activity and cellular invasiveness. Here, we analyzed the mRNA expression signature of a constitutively active C‐terminal mutant of c‐Src, c‐Src(mt), in comparison with its wild‐type protein, c‐Src(wt), in the human non‐transformed breast epithelial cell line MCF‐10A. We demonstrated previously that the mutant altered migratory and metastatic properties. Genome‐wide transcriptome analysis revealed that c‐Src(mt) de‐regulated the expression levels of approximately 430 mRNAs whose gene products are mainly involved in the cellular processes of migration and adhesion, apoptosis and protein synthesis. 82.9% of these genes have previously been linked to cellular migration, while the others play roles in RNA transport and splicing processes, for instance. Consistent with the transcriptome data, cells expressing c‐Src(mt), but not those expressing c‐Src(wt), showed the capacity to metastasize into the lungs of mice in vivo. The mRNA expression profile of c‐Src(mt)‐expressing cells shows significant overlap with that of various primary human tumor samples, possibly reflecting elevated Src activity in some cancerous cells. Expression of c‐Src(mt) led to elevated migratory potential. We used this model system to analyze the transcriptional changes associated with an invasive cellular phenotype. These genes and pathways de‐regulated by c‐Src(mt) may provide suitable biomarkers or targets of therapeutic approaches for metastatic cells.

Database

This project was submitted to the National Center for Biotechnology Information BioProject under ID PRJNA288540. The Illumina RNA‐Seq reads are available in the National Center for Biotechnology Information Sequence Read Archive under study ID SRP060008 with accession numbers SRS977414 for MCF‐10A cells, SRS977717 for mock cells, SRS978053 for c‐Src(wt) cells and SRS978046 for c‐Src(mt) cells.
Very high cycle fatigue properties of high‐strength spring steel 60SiCrV7
Authors: Hui W. J. , Zhou C. , Zhang Y. J. , Zhao X. L. , Dong H.
Published: February 2016

The very high cycle fatigue properties of spring steel 60SiCrV7 for automotive suspension system with different hydrogen contents were studied by using ultrasonic fatigue testing and fatigue crack growth testing. The results show that the S–N curves exhibit continuous drop of fatigue lives and no obvious horizontal line exists. Similar fracture surface features were observed for all the specimens that failed mainly from internal inclusions with surrounding granular bright facet (GBF). Fatigue strength decreases remarkably with increasing hydrogen content. The applied stress intensity factor range at the periphery of GBF ΔKGBF is approximately proportional to 1/3 power of the square of GBF area. The average values of ΔKGBF for uncharged specimens are close to crack growth threshold ΔKth, which indicates that ΔKGBF could be regarded as the threshold value governing the beginning of stable fatigue crack propagation. The increase of hydrogen content tends to reduce ΔKGBF.
Estimation of three‐dimensional stress intensity factor for structural ‘T’ details
Authors: Shohel M. , Menzemer C. , Arthur G.A.
Published: February 2016

Three‐dimensional (3D) opening mode stress intensity factors (SIFs) for structural steel‐welded ‘T’ details were investigated by the finite element method. A 3D shape‐dependent correction factor is proposed for semi‐elliptical surface cracks. The aspect ratio (a/c) of a semi‐elliptical crack plays a key role in the approximation of 3D‐SIF values, and in the present study, it was estimated for a 3D crack analysis. The estimated 3D‐SIF was determined through a correlation between the a/c ratio and the two‐dimensional SIF for semi‐elliptical cracks in the thickness direction adjacent to the web‐flange junction of a welded ‘T’. The resulting equation can be used to estimate the 3D‐SIF values from the two‐dimensional SIF without much ambiguity.
Cellulosic feedstock production on Conservation Reserve Program land: potential yields and environmental effects
Authors: LeDuc Stephen D. , Zhang Xuesong , Clark Christopher M. , Izaurralde R. César
Published: February 2016

Producing biofuel feedstocks on current agricultural land raises questions of a ‘food‐vs.‐fuel’ trade‐off. The use of current or former Conservation Reserve Program (CRP) land offers an alternative; yet the volumes of ethanol that could be produced and the potential environmental impacts of such a policy are unclear. Here, we applied the Environmental Policy Integrated Climate model to a US Department of Agriculture database of over 200 000 CRP polygons in Iowa, USA, as a case study. We simulated yields and environmental impacts of growing three cellulosic biofuel feedstocks on CRP land: (i) an Alamo‐variety switchgrass (Panicum virgatum L.); (ii) a generalized mixture of C4 and C3 grasses; (iii) and no‐till corn (Zea mays L.) with residue removal. We simulated yields, soil erosion, and soil carbon (C) and nitrogen (N) stocks and fluxes. We found that although no‐till corn with residue removal produced approximately 2.6–4.4 times more ethanol per area compared to switchgrass and the grass mixture, it also led to 3.9–4.5 times more erosion, 4.4–5.2 times more cumulative N loss, and a 10% reduction in total soil carbon as opposed to a 6–11% increase. Switchgrass resulted in the best environmental outcomes even when expressed on a per liter ethanol basis. Our results suggest planting no‐till corn with residue removal should only be done on low slope soils to minimize environmental concerns. Overall, this analysis provides additional information to policy makers on the potential outcome and effects of producing biofuel feedstocks on current or former conservation lands.
Frances B. Lysnar: New Zealand's first woman FRGS, 1913
Authors: Roche Michael
Published: February 2016

In 1913 the Royal Geographical Society (RGS), in the face of mounting pressure, decided to readmit women as Fellows (FRGS). Amongst the first group of successful nominees was Frances B. Lysnar, a New Zealand teacher, amateur artist and traveller. This paper briefly positions Lynsar in colonial New Zealand and examines how she engaged with ‘geography’, revisits her book New Zealand: The Dear Old Maori Land (1915), and assesses how she used ‘FRGS’ status to give added credential to her work raising funds for Pandita Ramabai's Mukti Mission in India.
Plausible Primitives: Kafka and Jewish Primitivism
Authors: Spinner Samuel J.
Published: February 2016

This article analyzes Kafka's works as an exemplar of Jewish primitivism. The eastern European Jew had, from the turn of the century, become increasingly aestheticized and anthropologized, a confluence that bespeaks the concurrent and intertwined development of anthropology and of a modernist fascination with those who were identified as the authentic bearers of culture. Eastern European Jews became subjects for the exploration of ‘authentic’ culture much like South Seas Islanders, with the crucial difference lying in their linguistic, ethnic, religious, and geographic propinquity to the German‐speaking Jews of central Europe; this propinquity created what I term a plausible primitivism, the central defining characteristic of Jewish primitivism. This transferal of the ethnographic object from far away to near at hand offered a new mode of primitivism that privileged the ethnographic encounter over formalist primitivism. As such, it brought primitivist discourses into the center of debates over identity and modernity among German Jews.
Dental health status of community‐dwelling older Singaporeans: findings from a nationally representative survey
Authors: Chiu Chi‐Tsun , Malhotra Rahul , Tan See Mieng , Lim Jane , Chan Angelique , Teoh Khim Hean , Gan Sapphire Tsering , Saito Yasuhiko
Published: February 2016

Objectives

To assess the dental health status of older Singaporeans by age, gender and ethnicity.

Background

Poor dental health in elders has been linked to a number of adverse health conditions and is often associated with an increased risk of mortality in older people.

Materials and methods

Data came from a nationally representative cross‐sectional 2009 survey of community‐dwelling Singaporeans aged 60 and over. The distribution of the number of natural teeth, chewing ability and the presence of dentures were assessed by age, gender and ethnicity (Chinese/Malay/Indian) using sampling weights.

Results

With increasing age, there was a decrease in the average number of natural teeth, a decrease in the proportion of people with 20 or more natural teeth and with the strongest chewing ability, and an increase in the proportion that was edentulous or had dentures. Women, vs. men, had a lower average number of natural teeth (10.3 vs. 12.8), and they were more likely to be edentulous (37 vs. 24%) and to have dentures (73 vs. 63%). Across ethnic groups, Indians had the highest average number of natural teeth (17.0). However, among those who had dentures, Indians were the least likely to have the strongest chewing ability.

Conclusions

The findings demonstrated differences in dental health status by age, gender and ethnicity. They highlight the need for improvements in the dental health status of all older Singaporeans, especially older women. The data presented herein may serve as a baseline for policymakers to evaluate the impact of recent schemes launched by the Ministry of Health (Singapore) to subsidise dental treatment.
Comprehension of Japanese oral care‐related terms among caregivers and nurses, as assessed using a newly developed instrument
Authors: Shibata Satoko , Stegaroiu Roxana , Nakazawa Akari , Ohuchi Akitsugu
Published: February 2016

Objectives

(i) To assess comprehension of oral care‐related terms among caregivers and nurses working at long‐term care facilities, using a newly developed test; (ii) to analyse the effect of participant characteristics on their comprehension.

Background

Effective mutual communication between dental professionals and caregivers/nurses is essential for providing information on daily oral care for institutionalised elders.

Methods

A 36‐item word‐knowledge test in Japanese was developed to assess comprehension of oral care‐related terms. The test was administered to a convenience sample of 236 nursing staff (198 caregivers and 38 nurses) at six long‐term care facilities in Niigata City, Japan, and its reliability and validity were verified. Associations of participant characteristics with their responses were investigated by multiple regression analysis.

Results

Mean percentage of correct responses (accuracy rate) for nursing staff was approximately 62% (highest for oral care products and lowest for prosthodontic terms). Test internal reliability was high (Cronbach's alpha >0.8). Concurrent validity (test ability to distinguish between characteristically different groups) was confirmed. Mean accuracy rate was significantly higher among nurses (78.5 ± 19.3%) than among caregivers (58.7 ± 22.8%), and among respondents with interest in oral care (64.2 ± 21.1%) than among those with no such interest (51.5 ± 28.9%).

Conclusion

The word‐knowledge test was valid and reliable for nursing staff of six long‐term care facilities in Niigata City. Their comprehension was low for perioral and intraoral structures, related symptom and disease names, and prosthodontics terms related to oral care. Understanding of oral care‐related terms among the nursing staff was related to their occupation and interest in oral care.
Early plant community dynamics following overseeding for the rehabilitation of a Mediterranean silvopastoral system
Authors: Franca Antonello , Caredda Salvatore , Sanna Federico , Fava Francesco , Seddaiu Giovanna
Published: February 2016

The sowing of selected seeds is often applied as post‐fire rehabilitation practice in Mediterranean silvopastoral systems. Often, the topography of these silvopastoral systems is sloppy and irregular, requiring low input and easy pasture rehabilitation practices, such as no tillage, low seed and fertilizer rates. In this paper, we studied the vegetation changes over 4 years, after a low‐input overseeding (broadcasting) of non‐native pasture species, within a post‐fire rehabilitation program of a silvopastoral system in Sardinia (Italy). The main objective was to assess the effect of overseeding on the early plant community dynamics and on the relationship between topography, soil pH, and soil nitrogen content on the spatial and temporal dynamics of the grassland composition. Understorey vegetation was classified into nine “functional classes”, three corresponding to the oversown species (subclovers, burr medic and annual ryegrass) and six belonging to the native community, i.e. grasses, legumes, Cistus spp., spiny Carduaceae, spiny Rubus spp. and other forbs. The oversown species showed a rapid establishment, contributing from 30 up to 50% to the floristic composition of the oversown pasture. The overseeding reduced the abundance of post‐fire invasive shrubs and spiny forbs by up to about 70% compared to the unsown pasture. The spatial patterns of the functional classes were only weakly influenced by nitrogen content, with a higher impact on introduced species in the first 2 years after overseeding, while the topographic variables had a desultory influence over the 4 years. Overseeding proved to be effective for the rehabilitation and improvement of semiarid Mediterranean grasslands without substantially constraining the ecological succession of floristic composition towards the native vegetation.
Effects of ITPA polymorphism on decrease of hemoglobin during simeprevir, peg‐interferon, and ribavirin combination treatment for chronic hepatitis C
Authors: Morio Kei , Imamura Michio , Kawakami Yoshiiku , Morio Reona , Hatooka Masahiro , Kan Hiromi , Fujino Hatsue , Fukuhara Takayuki , Kobayashi Tomoki , Masaki Keiichi , Ono Atsushi , Nakahara Takashi , Urabe Ayako , Yokoyama Satoe , Nagaoki Yuko , Kawaoka Tomokazu , Hiraga Nobuhiko , Tsuge Masataka , Hiramatsu Akira , Hayes C Nelson , Aikata Hiroshi , Ochi Hidenori , Chayama Kazuaki ,   Hiroshima Liver Study Group
Published: February 2016

Aim

Polymorphisms in the ITPA gene influence anemia during peg‐interferon (PEG‐IFN) and ribavirin (RBV) therapy, but their effects during triple therapy with simeprevir, PEG‐IFN, and RBV are not sufficiently known.

Methods

We analyzed 212 patients with genotype 1 chronic hepatitis C, who were treated with simeprevir plus PEG‐IFN/RBV triple therapy, and assessed the effect of the ITPA polymorphism on hemoglobin levels and RBV dose reduction. ITPA (rs1127354) and IFNL4 (ss469415590) polymorphisms were genotyped using the Invader assay. A stepwise multivariate regression analysis was carried out to identify factors associated with outcome of the therapy.

Results

Reduction of hemoglobin levels was similar between patients treated with simeprevir plus PEG‐IFN/RBV and those treated with PEG‐IFN/RBV therapy. In simeprevir plus PEG‐IFN/RBV‐treated patients, decreases in hemoglobin levels were faster and greater, and the cumulative proportion of patients with ribavirin dose reduction was significantly greater in ITPA genotype CC patients than in CA/AA patients. The total dose of simeprevir and PEG‐IFN was similar between ITPA genotype CC and CA/AA patients. In contrast, the total dose of RBV was lower in patients with the CC genotype. Multivariate analysis showed that the IFNL4 TT/TT genotype, but not the ITPA SNP genotype, treatment history (treatment‐naive or relapse during prior treatment), and treatment completion were significantly associated with outcome of therapy.

Conclusion

ITPA polymorphism influences hemoglobin levels and incidence of RVB dose reduction during simeprevir triple therapy, indicating the importance of monitoring anemia during treatment, particularly for ITPA genotype CC patients.
Dysplasia in Barrett's oesophagus: p53 immunostaining is more reproducible than haematoxylin and eosin diagnosis and improves overall reliability, while grading is poorly reproducible
Authors: Kaye Philip V , Ilyas Mohammad , Soomro Irshad , Haider Syeda A , Atwal Gurprit , Menon Sindhu , Gill Shafiq , Richards Cathy , Harrison Rebecca , West Kevin , Ragunath Krish
Published: February 2016

Aims

p53 immunostaining in Barrett's oesophagus (BO) has been shown to be predictive of progression, but data regarding its generalizability to routine practice are lacking. This study compared the reliability of p53 and dysplasia interpretation and grading.

Methods and results

Seventy‐two cases encompassing the full spectrum of BO were circulated to 10 pathologists from four institutions after a brief training session in p53 interpretation. Each pathologist classified cases on haematoxylin and eosin (H&E) alone using the Vienna classification and assessed the p53 staining using a qualitative system. Agreement was assessed using kappa statistics. For the four‐tier Vienna system, the average unweighted kappa was 0.30. Weighted kappa values varied from 0.27 to 0.69 with an average of 0.47. When grouped into definite dysplasia versus no definite dysplasia the average kappa was 0.55, but the kappa for low‐grade dysplasia (LGD) versus high‐grade dysplasia (HGD) was only 0.31. For p53, using the three recognized patterns, the unweighted kappa was 0.6 (confidence interval 0.58–0.63). When cases were evaluated with both H&E and p53 the average kappa was 0.61 for definite dysplasia versus the rest.

Conclusions

p53 immunohistochemistry interpretation is more reliable than dysplasia diagnosis, even with limited training. As it is predictive of prognosis and improves diagnostic reproducibility, it is suitable for routine use by pathologists as an adjunct to dysplasia diagnosis. The distinction of LGD versus HGD was poor. This study supports simplifying dysplasia diagnosis into ‘present’, ‘indefinite’ or ‘absent’, and the use of p53 as an ancillary marker in difficult cases. This should help to prevent overdiagnosis of dysplasia and inappropriate treatment.
New insights on the origin of troctolites from the breakaway area of the Godzilla Megamullion (Parece Vela back‐arc basin): The role of melt‐mantle interaction on the composition of the lower crust
Authors: Sanfilippo Alessio , Dick Henry J. B. , Ohara Yasuhiko , Tiepolo Massimo
Published: February 2016

The troctolites and olivine‐gabbros from the Dive 6 K‐1147 represent the most primitive gabbroic rocks collected at the Godzilla Megamullion, a giant oceanic core complex formed at an extinct spreading segment of the Parece Vela back‐arc basin (Philippine Sea). Previous investigations have shown that these rocks have textural and major elements mineral compositions consistent with a formation through multistage interaction between mantle‐derived melts and a pre‐existing ultramafic matrix. New investigations on trace element mineral compositions basically agree with this hypothesis. Clinopyroxenes and plagioclase have incompatible element signatures similar to that of typical‐MORB. However, the clinopyroxenes show very high Cr contents (similar to those of mantle clinopyroxene) and rim having sharply higher Zr/REE ratios with respect to the core. These features are in contrast with an evolution constrained by fractional crystallization processes, and suggest that the clinopyroxene compositions are controlled by melt‐rock interaction processes. The plagioclase anorthite versus clinopyroxene Mg#[Mg/(Mg + FeTot)] correlation of the Dive 6 K‐1147 rocks shows a trend much steeper than those depicted by other oceanic gabbroic sections. Using a thermodynamic model, we show that this trend is reproducible by fractionation of melts assimilating 1 g of mantle peridotite per 1 °C of cooling. This model predicts the early crystallization of high Mg# clinopyroxene, consistent with our petrological observation. The melt‐peridotite interaction process produces Na‐rich melts causing the crystallization of plagioclase with low anorthite component, typically characterizing the evolved gabbros from Godzilla Megamullion.
Consumers as innovators in the electricity sector? Consumer perceptions on smart grid services
Authors: Heiskanen Eva , Matschoss Kaisa
Published: February 2016

This article assesses the possibilities of using consumer innovation in the electricity sector, which is slow‐moving, yet faced with huge challenges and opportunities to become “smart” and “low carbon.” We study the benefits of engaging innovative consumers (“lead users”) in product, service, and business innovation in terms of (a) the capacity of lead user‐consumers to innovate in the highly regulated electricity market, (b) the attractiveness of such lead‐user generated ideas for mainstream consumers, (c) the usefulness of lead‐user engagement for companies in the energy industry, and (d) the usefulness of lead user engagement for the necessary broader societal transition processes. We conclude that consumers can stimulate industry‐wide innovation even in challenging contexts like “smart” and “low‐carbon” solutions and the highly regulated energy industry. Lead user‐consumers can also articulate societal and social responsibility concerns that are relevant for the entire market.
Infants Use Statistical Sampling to Understand the Psychological World
Authors: Wellman Henry M. , Kushnir Tamar , Xu Fei , Brink Kimberly A.
Published: February 2016

Preverbal infants engage in statistical and probabilistic inference to learn about their linguistic and physical worlds. Do they also employ probabilistic information to understand their social world? Do they infer underlying causal mechanisms from statistical data? Here, we show, with looking‐time methods, that 10‐month‐olds attend to statistical information to understand their social–psychological world and plausibly infer underlying causal mechanisms from violations of physical probabilities.