bluuebunny/crossref_metadata_2025 huggingface dataset:
Oestrogen inhibits BMP4‐induced BMP4 expression in cardiomyocytes: a potential mechanism of oestrogen‐mediated protection against cardiac hypertrophy
Authors: Wang Yu‐Chun , Xiao Xiao‐Lin , Li Na , Yang Di , Xing Yue , Huo Rong , Liu Ming‐Yu , Zhang Yan‐Qiu , Dong De‐Li
Published: October 2014

Background and Purpose

Oestrogen inhibits cardiac hypertrophy and bone morphogenetic protein‐4 (BMP4) induces cardiac hypertrophy. Here we have studied the inhibition by oestrogen of BMP4 expression in cardiomyocytes.

Experimental Approach

Cultures of neonatal rat cardiomyocytes were used in in vitro experiments. Bilatαl ovariectomy (OVX) was carried out in female Kunming mice and cardiac hypertrophy was induced by transverse aortic constriction (TAC).

Key Results

Oestrogen inhibited BMP4‐induced cardiomyocyte hypertrophy and BMP4 expression in vitro. The inhibition of BMP4‐induced BMP4 protein expression by oestrogen was prevented by the inhibitor of oestrogen receptor‐β, PHTPP, but not by the inhibitor of oestrogen receptor‐α MPP. BMP4 induced smad1/5/8 activation, which was not affected by oestrogen in cardiomyocytes. BMP4 induced JNK but not ERK1/2 and p38 activation, and activated JNK was inhibited by oestrogen. Treatment with the p38 inhibitor SB203580 or the JNK inhibitor SP600125 inhibited BMP4‐induced BMP4 expression in cardiomyocytes, but the ERK1/2 inhibitor U0126 increased BMP4‐induced BMP4 expression, indicating that JNK, ERK1/2 and p38 MAPKs were all involved, although only JNK activation contributed to the inhibition of BMP4‐induced BMP4 expression by oestrogen. TAC induced significant heart hypertrophy in OVX mice in vivo and oestrogen replacement inhibited TAC‐induced heart hypertrophy in OVX mice. In parallel with the data of heart hypertrophy, oestrogen replacement significantly reduced the increased BMP4 protein expression in TAC‐treated OVX mice.

Conclusions and Implications

Oestrogen treatment inhibited BMP4‐induced BMP4 expression in cardiomyocytes through stimulating oestrogen receptor‐β and inhibiting JNK activation. Our results provide a novel mechanism underlying oestrogen‐mediated protection against cardiac hypertrophy.

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
Synthesis and Antitumor Activity of Natural Compound Aloe Emodin Derivatives
Authors: Thimmegowda Naraganahalli R. , Park Chanmi , Shwetha Bettaswamigowda , Sakchaisri Krisada , Liu Kangdong , Hwang Joonsung , Lee Sangku , Jeong Sook J. , Soung Nak K. , Jang Jae H. , Ryoo In‐Ja , Ahn Jong S. , Erikson Raymond L. , Kim Bo Y.
Published: October 2014

In this study, we have synthesized novel water soluble derivatives of natural compound aloe emodin 4(a–j) by coupling with various amino acid esters and substituted aromatic amines, in an attempt to improve the anticancer activity and to explore the structure–activity relationships. The structures of the compounds were determined by 1H NMR and mass spectroscopy. Cell growth inhibition assays revealed that the aloe emodin derivatives 4d, 4f, and 4i effectively decreased the growth of HepG2 (human liver cancer cells) and NCI‐H460 (human lung cancer cells) and some of the derivatives exhibited comparable antitumor activity against HeLa (Human epithelial carcinoma cells) and PC3 (prostate cancer cells) cell lines compared to that of the parent aloe emodin at low micromolar concentrations.
Teaching Lean Six Sigma within A Supply Chain Context: The Airplane Supply Chain Simulation
Authors: Ellis Scott C. , Goldsby Thomas J. , Bailey Ana M. , Oh Jae‐Young
Published: October 2014

Lean six sigma is a management methodology that firms can employ to achieve substantial improvement in supply chain performance. However, few pedagogical exercises facilitate students’ use of a comprehensive set of lean six sigma principles within a supply chain context. We describe the Airplane Supply Chain Simulation that helps students understand how lean six sigma concepts may be leveraged to improve supply chain performance. The basis of this simulation is a four‐tier supply chain, consisting of suppliers (two tiers), a manufacturer, and a customer, that produces three models of paper airplanes to meet randomly distributed customer demand. In the first of three successive runs, a highly structured simulation is executed in which supply chain roles are well defined, material flows are convoluted, and a “push” production strategy is followed. The first simulation as the “current state” and, for the second and third simulation runs, challenge competing student teams to leverage lean six sigma concepts to develop a “future state” that enables the fulfillment of all customer orders at the lowest cost. Results based on statistical analyses of survey response data from 194 MBA students show that the Airplane Supply Chain Simulation is an effective participative, team‐based learning tool.
Using Contests to Provide Business Students Project‐Based Learning in Humanitarian Logistics: PSAid Example
Authors: Özpolat Koray , Chen Yuwen , Hales Doug , Yu Degan , Yalcin Mehmet G.
Published: October 2014

Business students appreciate working on classroom projects that are both enjoyable and useful in preparing them for future careers. Promoting competition among project teams is also used as a method to motivate students. The Humanitarian Logistics Project (HLP) teaches undergraduate students the logistical implications of unsolicited material donations in disaster relief. To encourage competition, students are organized into teams of three and tasked with designing humanitarian public service announcements (PSAs) that improve their understanding of humanitarian issues in the general public. These announcements are then submitted to the national PSAid (Public Service Announcements for International Disasters) contest for American college students. The exercise is rigorous because it requires students to collect logistical data and use it to communicate the principle of smart compassion to the public in a creative fashion. Moreover, not only do students learn about topics related to humanitarian logistics by competing with other college students nation‐wide, but also do they make a socially responsible contribution to the public. Analysis of survey data shows that students’ learning outcomes from the HLP are significantly greater than those for other supply chain topics covered in class, and that student satisfaction with the HLP is high.
W. H. Hutt (1899–1988): Free Markets and Social Justice
Authors: Dawson Graham
Published: October 2014

W.H. Hutt reaffirmed the principles of classical economics and classical liberalism and, by applying them to urgent issues he observed in the world around him, he demonstrated the contemporary relevance of freedom and competitive institutions. A wide‐ranging critique of Keynes was founded upon a classical analysis of the labour market, while his trenchant opposition to apartheid advanced along economic and political paths. Hutt questioned the justice of the accumulation of wealth from the exploitation of monopoly power over generations. In all of these respects there are affinities between Hutt's thought and that of ‘Bleeding Heart Libertarians’.
Involvement of interleukin‐21 in the pathophysiology of aplastic anemia
Authors: Zhang Jizhou , Wu Qingqing , Shi Jun , Ge Meili , Li Xingxin , Shao Yingqi , Yao Jianfeng , Zheng Yizhou
Published: October 2014

Objective

Recently enhanced T‐helper type 17 (Th17) immune responses and deficient CD4+CD25hiFoxP3+ regulatory T cells (Tregs) have been reported in acquired aplastic anemia (AA). Interleukin‐21 (IL‐21), a CD4+ T‐cell‐derived proinflammatory cytokine, modulates the balance between Th17 cells and Tregs. However, its role in AA remains unclear.

Methods

IL‐21 gene expression was examined by quantitative real‐time PCR. Cytokines in plasma and cell culture supernatants were detected by ELISA. Cytokines‐producing T cells and Tregs were evaluated by flow cytometry.

Results

IL‐21 mRNA levels in circulating CD4+ T cells and IL‐21 levels in blood plasma were markedly increased in patients with newly diagnosed AA. Moreover, elevated IL‐21‐producing CD4+ T cells were accompanied by Th17 cells accumulation and Tregs decrease, and correlated with AA activity. In vitro, IL‐21 not only inhibited the expression of FoxP3, but also induced the expression of IL‐17 in CD4+ T cells of AA patients. More importantly, we found that T cells within the bone marrow (BM) of AA patients were in a heightened activation state, which may be related to IL‐21.

Conclusion

Our data suggested a critical role of IL‐21 in breaking immune homeostasis in AA by promoting Th17 cells, activating BM T cells and suppressing Tregs.
Runt‐related transcription factor 2 attenuates the transcriptional activity as well as DNA damage‐mediated induction of pro‐apoptotic TAp73 to regulate chemosensitivity
Authors: Ozaki Toshinori , Sugimoto Hirokazu , Nakamura Mizuyo , Hiraoka Kiriko , Yoda Hiroyuki , Sang Meixiang , Fujiwara Kyoko , Nagase Hiroki
Published: October 2014

Although runt‐related transcription factor 2 (RUNX2) is known to be an essential key transcription factor for osteoblast differentiation and bone formation, RUNX2 also plays a pivotal role in the regulation of p53‐dependent DNA damage response. In the present study, we report that, in addition to p53, RUNX2 downregulates pro‐apoptotic TAp73 during DNA damage‐dependent cell death. Upon adriamycin (ADR) exposure, human osteosarcoma‐derived U2OS cells underwent cell death in association with an upregulation of TAp73 and various p53/TAp73‐target gene products together with RUNX2. Small interfering RNA‐mediated silencing of p73 resulted in a marked reduction in ADR‐induced p53/TAp73‐target gene expression, suggesting that TAp73 is responsible for the ADR‐dependent DNA damage response. Immunoprecipitation and transient transfection experiments demonstrated that RUNX2 forms a complex with TAp73 and impairs its transcriptional activity. Notably, knockdown of RUNX2 stimulated ADR‐induced cell death accompanied by a massive induction of TAp73 expression, indicating that RUNX2 downregulates TAp73 expression. Consistent with this notion, the overexpression of RUNX2 suppressed ADR‐dependent cell death, which was associated with a remarkable downregulation of TAp73 and p53/TAp73‐target gene expression. Collectively, our present findings strongly suggest that RUNX2 attenuates the transcriptional activity and ADR‐mediated induction of TAp73, and may provide novel insights into understanding the molecular basis behind the development and/or maintenance of chemoresistance. Thus, we propose that the silencing of RUNX2 might be an attractive strategy for improving the chemosensitivity of malignant cancers.

Structured digital abstract

p73 and RUNX2 colocalize by fluorescence microscopy (View interaction)

RUNX2 physically interacts with p73 by anti bait coip (1, 2)
Market Liquidity and Ambiguity: The Certification Role of Corporate Governance
Authors: X. Jiang Christine , Kim Jang‐Chul , Kuvvet Emre
Published: October 2014

We investigate how firm‐specific certification practices through corporate governance can reduce perceived ambiguity and thus enhance liquidity of a firm in the stock market. We show that better corporate governance helps reduce ambiguity. In addition, a reduction in ambiguity is significantly related to higher liquidity of firms. Our results are robust to alternative model specifications and measures of ambiguity, and remain statistically significant after controlling for other known determinants of ambiguity and liquidity. Our results shed light on how ambiguity can be moderated through firm‐level certification practices and on the channel through which a moderation of ambiguity affects shareholder wealth.
Long‐term change in a behavioural trait: truncated spawning distribution and demography in Northeast Arctic cod
Authors: Opdal Anders Frugård , Jørgensen Christian
Published: October 2014

Harvesting may be a potent driver of demographic change and contemporary evolution, which both may have great impacts on animal populations. Research has focused on changes in phenotypic traits that are easily quantifiable and for which time series exist, such as size, age, sex, or gonad size, whereas potential changes in behavioural traits have been under‐studied. Here, we analyse potential drivers of long‐term changes in a behavioural trait for the Northeast Arctic stock of Atlantic cod Gadus morhua, namely choice of spawning location. For 104 years (1866–1969), commercial catches were recorded annually and reported by county along the Norwegian coast. During this time period, spawning ground distribution has fluctuated with a trend towards more northerly spawning. Spawning location is analysed against a suite of explanatory factors including climate, fishing pressure, density dependence, and demography. We find that demography (age or age at maturation) had the highest explanatory power for variation in spawning location, while climate had a limited effect below statistical significance. As to potential mechanisms, some effects of climate may act through demography, and explanatory variables for demography may also have absorbed direct evolutionary change in migration distance for which proxies were unavailable. Despite these caveats, we argue that fishing mortality, either through demographic or evolutionary change, has served as an effective driver for changing spawning locations in cod, and that additional explanatory factors related to climate add no significant information.
Genetic background and risk of postpartum haemorrhage: results from an Italian cohort of 3219 women
Authors: Biguzzi E. , Franchi F. , Acaia B. , Ossola W. , Nava U. , Paraboschi E. M. , Asselta R. , Peyvandi F.
Published: October 2014

Postpartum haemorrhage (PPH) is a leading cause of maternal mortality, particularly in the developing countries, and of severe maternal morbidity worldwide. To investigate the impact of genetic influences on postpartum haemorrhage, in association with maternal and intrapartum risk factors, using a candidate gene approach. All women (n = 6694) who underwent a vaginal delivery at the Obstetric Unit of a large University hospital in Milan (Italy) between July 2007 and September 2009 were enrolled. The first consecutive 3219 women entered the genetic study. Postpartum haemorrhage was defined as ≥500 mL blood loss. Eight functional polymorphisms in seven candidate genes were chosen because of their potential role in predisposing to or protecting from haemorrhagic conditions: tissue factor (F3), factor V (F5), tissue factor pathway inhibitor (TFPI), platelet glycoprotein Ia/IIa (ITGA2), prothrombin (F2), platelet glycoproteins Ibα (GP1BA) and angiotensin‐converting enzyme (ACE). After correction for the already known PPH risk factors, only the promoter polymorphism of the tissue factor gene (F3 ‐603A>G) showed a significant association with PPH, the G allele exerting a protective effect (P = 0.00053; OR = 0.79, 95% CI = 0.69–0.90). The protective effect against PPH of the TF ‐603A>G polymorphism is biologically plausible since the G allele is associated with an increased protein expression and Tissue Factor is strongly represented in the placenta at term, particularly in decidual cells of maternal origin.
Postpartum von Willebrand factor levels in women with and without von Willebrand disease and implications for prophylaxis
Authors: James A. H. , Konkle B. A. , Kouides P. , Ragni M. V. , Thames B. , Gupta S. , Sood S. , Fletcher S. K. , Philipp C. S.
Published: October 2014

The aim of this study was to elucidate the fall in von Willebrand factor (VWF) and factor VIII activity (FVIII) after childbirth in women with and without von Willebrand disease (VWD). VWF:RCo, VWF:Ag, and FVIII were obtained in the third trimester of pregnancy, on admission for childbirth, and 10 times postpartum. Specimens were processed within 4 h and analysed centrally. Means were calculated at each time point. Forty women (40 pregnancies) without VWD and 32 women (35 pregnancies) with VWD were enrolled. 15/32 with VWD were treated (30% of those with type 1 and all of those with type 2) in 17 pregnancies. Treatments prior to delivery consisted of desmopressin (2/17), VWF concentrate (15/17) and after delivery VWF concentrate (16/17). Duration of treatment was 0–21 days (median 6). VWF levels peaked at 250% of baseline – 4 h postpartum in women with VWD and 12 h postpartum in women without VWD. Thereafter, VWF levels fell rapidly, approached baseline at 1 week and reached baseline at 3 weeks. Except immediately postpartum, when the levels among treated cases were higher, levels among women with VWD appeared to parallel, but were lower than those among women without VWD. Levels were lowest among those who received treatment. VWF levels fall rapidly after childbirth. Except immediately postpartum, current treatment strategies do not raise VWF levels to the levels of women without VWD or even to the levels of women with milder, untreated VWD. Consequently, women with VWD may be at risk of postpartum haemorrhage despite treatment.
An artificial nesting substrate for Osmia species that nest under stones, with focus on Osmia inermis (Hymenoptera: Megachilidae)
Authors: Sheffield Cory S. , Wilkes Margie A. , Christopher Cutler G. , Hermanutz Luise
Published: October 2014

Several megachilid bees are excellent crop pollinators, and many species show potential for management as they nest in pre‐existing cavities in artificial substrates. Some species, particularly in the Osmiini, however, have nesting habits not conducive to conventional trap‐nesting. Here we report on an artificial nest for species of Osmia bees which normally build nests on the underside of stones.

The Holarctic species Osmia inermis accepted overturned terracotta saucers as nesting sites, with 10% of the saucers occupied in the fall of 2011.

These saucers are inexpensive and available in many sizes, facilitating further scientific study of this, and other species. Implications of using artificial nests for managing this bee for crop pollination, and for its conservation, are discussed.
Discapacidad y absentismo. Análisis empírico sobre seis países europeos
Authors: GARCÍA SERRANO Carlos , MALO Miguel Á.
Published: October 2014

A partir de datos del Panel de Hogares de la Unión Europea (PHOGUE) sobre Austria, España, Grecia, Irlanda, Italia y Portugal de 1995–2001 se examina la influencia de la discapacidad en el absentismo laboral utilizando tres variables: el estado de salud autoevaluado, el número de visitas al médico y el número de noches de ingreso en hospital. Según los resultados, el absentismo entre los trabajadores con discapacidad es mayor. La gravedad de la discapacidad también tiene influencia. El efecto total de la discapacidad en el absentismo representa un incremento marginal de entre 6 y 26 días de ausencia al año (dependiendo del país).
The Absorption Profile of Pregabalin in Chronic Pancreatitis
Authors: Olesen Anne E. , Olofsen Erik , Olesen Søren S. , Staahl Camilla , Andresen Trine , Dahan Albert , Drewes Asbjørn M.
Published: October 2014

It was recently shown that pregabalin decreased pain associated with chronic pancreatitis. It is well known that pancreatitis patients suffer from fat malabsorption with accompanying diarrhoea because of loss of exocrine pancreatic enzyme production. This may lead to changes in the mucosal surface in the small intestine and possibly affect the absorption of pregabalin. The pharmacokinetics of pregabalin has never been investigated in patients suffering from chronic pancreatitis. The aim of this study was to develop a population pharmacokinetic model of pregabalin administered to patients with chronic pancreatitis. The pregabalin population pharmacokinetic analysis was conducted on data from fifteen patients with chronic pancreatitis. Each patient received 75 mg of pregabalin (oral capsule). Pregabalin concentrations were measured using a validated liquid chromatographic method. Data analysis was performed using non‐linear mixed effects modelling methodology as implemented by NONMEM. A one‐compartment model with first‐order absorption and elimination adequately described pregabalin pharmacokinetics. Time to maximum observed plasma concentration (Tmax) was 1.53 (95% CI 1.09–2.05). The maximum plasma concentration (Cmax) was 1.98 μg/ml (95% CI 1.69–2.34), and area under the plasma concentration–time profile (area under the curve) was 18.2 μg*hr/ml (95% CI 14.7–26.3). Pregabalin is well absorbed in patients with chronic pancreatitis, and the pharmacokinetic profile of pregabalin is not extensively affected by chronic pancreatitis.
Measuring cognitive load in test items: static graphics versus animated graphics
Authors: Dindar M. , Kabakçı Yurdakul I. , Dönmez F. I.
Published: October 2014

The majority of multimedia learning studies focus on the use of graphics in learning process but very few of them examine the role of graphics in testing students' knowledge. This study investigates the use of static graphics versus animated graphics in a computer‐based English achievement test from a cognitive load theory perspective. Three hundred and three 7th‐grade students were randomly split into two groups and given the test questions either with static graphics or with animated graphics accompanied with text. Students' response time, response accuracy, self‐reported ratings on cognitive load and secondary task approach were used to measure their cognitive load. Findings revealed that animating graphics increased the response time and secondary task scores of the students but did not have any significant effect on their test success. Furthermore, no difference was observed in self‐reported cognitive loads. The relationship between the four different cognitive load measures was also examined in the study. No direct relation was found between self‐reported ratings and secondary task scores. On the other hand, self‐ratings and response accuracy were found to be more sensitive to intrinsic cognitive load, whereas response time and secondary task measures were found to be more sensitive to extraneous cognitive load in our testing environment.
Mortality and weight loss of Atlantic salmon, Salmon salar L., experimentally infected with salmonid alphavirus subtype 2 and subtype 3 isolates from Norway
Authors: Taksdal T , Bang Jensen B , Böckerman I , McLoughlin M F , Hjortaas M J , Ramstad A , Sindre H
Published: October 2014

Pancreas disease (PD) caused by salmonid alphavirus (SAV) has a significant negative economic impact in the salmonid fish farming industry in northern Europe. Until recently, only SAV subtype 3 was present in Norwegian fish farms. However, in 2011, a marine SAV 2 subtype was detected in a fish farm outside the PD‐endemic zone. This subtype has spread rapidly among fish farms in mid‐Norway. The PD mortality in several farms has been lower than expected, although high mortality has also been reported. In this situation, the industry and the authorities needed scientific‐based information about the virulence of the marine SAV 2 strain in Norway to decide how to handle this new situation. Atlantic salmon post‐smolts were experimentally infected with SAV 2 and SAV 3 strains from six different PD cases in Norway. SAV 3‐infected fish showed higher mortality than SAV 2‐infected fish. Among the SAV 3 isolates, two isolates gave higher mortality than the third one. At the end of the experiment, fish in all SAV‐infected groups had significantly lower weight than the uninfected control fish. This is the first published paper on PD to document that waterborne infection produced significantly higher mortality than intraperitoneal injection.
Global Supply Chains of Coltan
Authors: Moran Daniel , McBain Darian , Kanemoto Keiichiro , Lenzen Manfred , Geschke Arne
Published: October 2014

The spot price for tantalum, a metal used in high‐performance consumer electronics, spiked in 2000, triggering a boom in artisanal mining of surface deposits in the Democratic Republic of Congo (DRC). The profit from columbite‐tantalite ore, or coltan, is alleged to have funded militants during that country's civil war. One warlord famously claimed that in 2000, coltan delivered a million dollars per month. While coltan mining was neither a necessary nor sufficient cause for the civil war, there is nevertheless a clear association between mining and conflict. In order to trace global flows of coltan out of the DRC, we used a high‐resolution multiregion input‐output (MRIO) table and a hybrid life cycle assessment (LCA) approach to trace exports through international supply chains in order to estimate a “coltan footprint” for various products. In this case study, our aim is to highlight the power and utility of hybrid LCA analysis using high‐resolution global MRIO accounts. We estimate which supply chains, nations, and consumer goods carry the largest loads of embodied coltan. This hybrid LCA case study provides estimates on illicit flows of coltan, estimates a coltan footprint of consumption, and highlights the advantages and challenges of using hybrid monetary‐physical input‐output/LCA approaches to study and quantify a negative social impact as an input to production. If successful, the hybrid LCA approach could be a useful and expedient measurement tool for understanding flows of conflict minerals embodied in supply chains.
Assessment of effects of mifepristone administration to lactating mice on the development and fertility of their progeny
Authors: Su Qian‐Qian , Huang Xiao‐Li , Qin Jiao , Liu Quan‐Sheng
Published: October 2014

Aim

Mifepristone, a synthetic steroid compound that induces abortion, was recently found to potentially pass into human milk. This study aimed to determine the effects of mifepristone administration to lactating mice on the development and reproduction of their progeny.

Methods

Lactating mice were gavage fed with mifepristone (8 mg/kg) daily for 4 days either from days 1–4 or from days 7–10 of lactation; controls received only peanut oil. Growth, mortality rate, organ weight to bodyweight ratio, sex hormone at 20, 40 and 60 days, fertility of these F1 progeny and litter size, sex ratio and mortality rate of the second generation were recorded.

Results

No significant differences were observed in the average bodyweight, mortality rate of the female or male pups, and organ coefficient of uterus and ovaries of females in adulthood in comparison with the controls. However, the organ coefficient of testis at day 20 and 40 and testosterone concentration at day 60 were increased in male pups. Moreover, the reproductive capacity of the F1 pups was unaffected by 4 days exposure to mifepristone via their mother's milk: time to birth of F2 pups, litter size, sex ratio and mortality rate were similar to control F1 pups.

Conclusion

The study showed that treating lactating mice with 8 mg/kg mifepristone influenced only the organ coefficient of testis at day 40 and the testosterone concentration in male pups at day 60, however, it did not affect the development and fertility of female and male pups.
Sooty Mould on Hibiscus rosa‐sinensis Caused by Leptoxyphium kurandae is Associated with Extrafloral Nectaries
Authors: Park Ji‐Hyun , Cho Sung‐Eun , Hong Sun‐Hee , Choi In‐Young , Shin Hyeon‐Dong
Published: October 2014

In August 2013, sooty mould was observed on Chinese hibiscus (Hibiscus rosa‐sinensis) in a propagation nursery in Seoul, Korea. The sooty mould initially developed at the junction between the leaf blade and leaf petiole and then dispersed along the vein on the abaxial surface. The fungal growth pattern on the plants was quite different from general sooty moulds growing on honeydew secreted by insects on the plants. On the basis of the morphological characteristics and phylogenetic analysis using the internal transcribed spacer rDNA, this fungus was identified as Leptoxyphium kurandae. A pathogenicity test was carried out to fulfil Koch's postulates. Through field observation and a pathogenicity test, we found an association between the sooty mould and extrafloral nectaries. To our knowledge, this is the first report of sooty mould caused by L. kurandae on the extrafloral nectaries of H. rosa‐sinensis.
The Effects of Knowledge Depth and Scope on the Relationship betweenR&DAlliances and New Product Development
Authors: Caner Turanay , Tyler Beverly B.
Published: October 2014

In this study, we extend the new product development (NPD) literature that proposes that firms' knowledge depth, defined as the reuse of well understood technical knowledge, and scope, defined as the use of newly acquired technical knowledge, and new knowledge accessed fromR&Dalliances all positively impactNPD. Building on the knowledge‐based view of the firm, we posit that the impact of firms'R&Dalliances is limited when their internal knowledge depth and scope are adequate forNPDneeds. We suggest that although firms formR&Dalliances to gain the right to access external knowledge ofR&Dalliance partners, they are not obligated to invest in resources to integrate external knowledge fromR&Dalliances. We propose that they wait to see if their internal knowledge depth and scope prove sufficient forNPD. If the external knowledge proves to be unnecessary, firms choose not to invest the resources required to integrate this knowledge with their internal knowledge. Alternatively, we suggest an increased impact ofR&Dalliances onNPDwhen firms are more limited in their internal knowledge depth and scope. We propose that when knowledge depth and scope prove insufficient, firms make the additional investments required to integrate external knowledge fromR&Dalliances with their internal knowledge stock. This reasoning is consistent with real options theory as it has been applied in alliance research, where strategic alliances are characterized as real options. We find support for our hypotheses using panel data of 738 firm year observations for 143U.S. biopharmaceutical firms operating in 2007. Our study contributes to theNPDliterature and suggests new directions for future research.
Interspecies allometric meta‐analysis of the comparative pharmacokinetics of 85 drugs across veterinary and laboratory animal species
Authors: Huang Q. , Gehring R. , Tell L. A. , Li M. , Riviere J. E.
Published: October 2014

Allometric scaling is widely used for the determination of first dosage regimen and the interpolation or extrapolation of pharmacokinetic parameters across many animal species during drug development. In this article, 85 drugs used in veterinary medicine obtained from the Food Animal Residue Avoidance Databank database were selected for allometric scaling analysis. Outlier species were identified by statistical methods. The results showed that 77% and 88% of drugs displayed significant correlations between total systemic clearance (CL) and volume of distribution at steady status (Vss) vs. body weight (P < 0.05) on a log‐log scale, respectively. The distribution of the allometric exponent b for CL and Vss displays approximate normal distribution, with means (0.87 and 0.99) and standard deviations (0.143 and 0.157) for CL and Vss, respectively. Twelve drugs were identified to have at least one outlier species for CL and ten drugs for Vss. The human CL and Vss were predicted for selected drugs by the obtained allometric equations. The predicted CL and Vss were within a threefold error compared to observed values, except the predicted CL values for antipyrine, warfarin and diazepam. The results can be used to estimate cross‐species pharmacokinetic profiles for predicting drug dosages in veterinary species, and to identify those species for which interpolation or extrapolation of pharmacokinetics properties may be problematic.
The hidden side of plant invasions: the role of genome size
Authors: Suda Jan , Meyerson Laura A. , Leitch Ilia J. , Pyšek Petr
Published: October 2014

The ecological role of genome size in plant biology, biogeography, and morphology has garnered increasing attention as the methods and technology associated with measuring cytological characteristics have become more reliable and accessible. However, how plant genome size influences plant invasions and at what stage in the invasion this influence occurs have been little explored. Several large‐scale analyses of published data have yielded valuable interspecific comparisons, but experimental studies that manipulate environmental factors are needed, particularly below the species level, to fully understand the role that genome size plays in plant invasion. In this review, we summarize the available knowledge, discuss the integration of genome size data into invasion research, and suggest how it can be applied to detect and manage invasive species. We also explore how global climate change could exert selective pressures on plant populations with varying genome sizes, thereby increasing the distribution range and invasiveness of some populations while decreasing others. Finally, we outline avenues for future research, including considerations of large‐scale studies of intraspecific variation in genome size of invasive populations, testing the interaction of genome size with other factors in macroecological analyses of invasions, as well as the role this trait may play in plant–enemy interactions.

Contents

Summary
994

I.
Introduction
994

II.
Genome size research meets invasion science: ecological, phenotypic and evolutionary consequences of variation in the amount of nuclear DNA in plants
997

III.
Applications of genome size data in species‐level invasion research
1001

IV.
Effect of climate change on genome size and invasion success
1002

V.
Gaps in knowledge and avenues for future research: towards closer integration of genome size knowledge into invasion ecology
1003

VI.
Conclusions
1004

Acknowledgements
1004

References
1005
Whole‐of‐society monitoring framework for sugar, salt, and fat consumption and noncommunicable diseases in India
Authors: Arora Narendra K. , Pillai Rakesh , Dasgupta Rajib , Garg Priyanka Rani
Published: October 2014

India has experienced a rising prevalence of cardiometabolic risk factors in the past 15 years: the prevalence of diabetes has increased from 5.9% to 9.1%, hypertension from 17.2% to 29.2%, and obesity from 4% to 15%. The increase is among all socioeconomic groups and in urban and rural populations, though the quantum of change varies. A concomitant increase in per capita consumption of sugar from 22 to 55.3 g/day and total fat from 21.2 to 54 g/day was observed, with significant differences between states of high and low human development index (HDI). Per capita consumption of sugar, salt, and fat is consistently and significantly associated with overweight and obesity but variably associated with the occurrence of hypertension and diabetes. Market research shows that approximately 50–60% of total salt, sugar, and fat in Indian markets is procured by bulk purchasers, generally for manufacturing processed food items. This sector of the Indian economy is among the fastest growing, with several policy incentives. It is not clear from most of the data sets whether available information on per capita sugar, salt, and fat consumption has considered the contribution of processed and ready‐to‐eat food items. The unprecedented changes of rapid urbanization, mechanization, and globalization demand close monitoring of social, developmental, and economic determinants. This paper provides pieces of evidence to justify a whole‐of‐society (WoS) framework for monitoring the inputs, processes, and behavioral components of the National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Disease and Stroke (NPCDCS) in India.
Mapping of minor quantitative trait loci (QTLs) conferring fertility restoration of wild abortive cytoplasmic male sterility and QTLs conferring stigma exsertion in rice
Authors: Li Pingbo , Su Gongche , Feng Fuchun , Wang Peng , Yu Sibin , He Yuqing
Published: October 2014

Cytoplasmic male sterility (CMS) hybrid rice has made a great contribution to the increase of rice yield globally. To facilitate the development of high‐quality pairs of the wild abortive (WA) male sterile and maintainer lines, the genetic basis of fertility restoration of WA‐CMS and stigma exsertion was investigated in this study using a testcross population with the WA‐CMS background. Seed‐setting rate and stigma exsertion rate were used as the indicators of the two traits, respectively. Results showed that four minor QTL regions from 9311 were responsible for the variation of seed‐setting rate, while a few minor QTLs and epistatic QTL pairs influenced stigma exsertion rate. These results would be of great use in the development of high‐quality pairs of WA male sterile and maintainer lines in rice.
Life concerns of elderly people living at home determined as by Community General Support Center staff: Implications for organizing a more effective integrated community care system. The Kurihara Project
Authors: Takada Junko , Meguro Kenichi , Sato Yuko , Chiba Yumiko ,   Kurihara Project members
Published: October 2014

Background

In Japan, the integrated community care system aims to enable people to continue to live in their homes. Based on the concept, one of the activities of a Community General Support Center (CGSC) is to provide preventive intervention based on a Community Support Program. Currently, a Basic Checklist (BC) is sent to elderly people to identify persons appropriate for a Secondary Prevention Program.

Methods

To find people who had not responded to the BC, CGSC staff evaluated the files of 592 subjects who had participated in the Kurihara Project to identify activities they cannot do that they did in the past, decreased activity levels at home, loss of interaction with people other than their family, and the need for medical interventions. This information was classified, when applicable, into the following categories: (A) ‘no life concerns’; (B) ‘undecided’; and (C) ‘life concerns’. The relationships between these classifications and clinical information, certified need for long‐term care, and items on the BC were examined.

Results

The numbers of subjects in categories A, B, and C were 291, 42, and 186, respectively. Life concerns were related to scores on the Clinical Dementia Rating, global cognitive function, depressive state, and apathy. Most items on the BC were not associated with classification into category C, but ≥25% of the subjects had life concerns related to these items.

Discussion

Assessment of life concerns by the CGSC staff has clinical validity. The results suggest that there are people who do not respond to the checklist or apply for Long‐Term Care Insurance, meaning that they ‘hide’ in the community, probably due to apathy or depressive state. To organize a more effective integrated community care system, the CGSC staff should focus mainly on preventive care.
Robust influence diagnostics for generalized linear models with continuous responses
Authors: Chien Li‐Chu , Tsou Tsung‐Shan
Published: October 2014

This article introduces two parametric robust diagnostic methods for detecting influential observations in the setting of generalized linear models with continuous responses. The legitimacy of the two proposed methods requires no knowledge of the true underlying distributions so long as their second moments exist. The performance of the two proposed influence diagnostic tools is investigated through limited simulation studies and the analyses of an illustration.
Urinary antibiotic activity in paediatric patients attending an outpatient department in north‐western Cambodia
Authors: Emary Katherine R. W. , Carter Michael J. , Pol Sreymom , Sona Soeng , Kumar Varun , Day Nicholas P. J. , Parry Christopher M. , Moore Catrin E.
Published: October 2014

Objective

Antibiotic resistance is a prominent public and global health concern. We investigated antibiotic use in children by determining the proportion of unselected children with antibacterial activity in their urine attending a paediatric outpatient department in Siem Reap, Cambodia.

Methods

Caregiver reports of medication history and presence of possible infection symptoms were collected in addition to urine samples. Urine antibiotic activity was estimated by exposing bacteria to urine specimens, including assessment against multiresistant bacteria previously isolated from patients in the hospital (a methicillin‐resistant Staphylococcus aureus (MRSA), a multiresistant Salmonella typhi and an extended‐spectrum β‐lactamase (ESBL)‐producing Escherichia coli isolate).

Results

Medication information and urine were collected from 775 children. Caregivers reported medication use in 69.0% of children in the preceding 48 h. 31.7% samples showed antibacterial activity; 16.3% showed activity against a local multiresistant organism. No specimens demonstrated activity against an ESBL‐producing E. coli.

Conclusions

Antibiotics are widely used in the community setting in Cambodia. Parents are often ill‐informed about drugs given to treat their children. Increasing the regulation and training of private pharmacies in Cambodia may be necessary. Regional surveillance of antibiotic use and resistance is also essential in devising preventive strategies against further development of antibiotic resistance, which would have both local and global consequences.
Sublethal effects of environmentally relevant run‐off concentrations of glyphosate in the root zone of Ludwigia peploides (creeping water primrose) and Polygonum hydropiperoides (smartweed)
Authors: Saunders Lyndsay E. , Pezeshki Reza
Published: October 2014

As one of the most widely applied agricultural chemicals in the world, glyphosate has many effects on the environment. The present study quantified plant responses to exposure by glyphosate through the root zone for a range of concentrations (0, 10, 100 and 1000 μg L−1). Ludwigia peploides and Polygonum hydropiperoides were grown in a greenhouse and given a single exposure to glyphosate via the root zone. The growth and physiological parameters were measured before exposure and for 18 days postexposure. The growth variables that were measured included the relative growth rate, stem length increase, biomass and root‐to‐shoot‐ratios. The physiological variables that were measured were the chlorophyll content index and chlorophyll fluorescence. The data analyses revealed that the root‐zone glyphosate affected some of the measured variables in P. hydropiperoides more than for L. peploides. Polygonum hydropiperoides showed a significant decrease in the root‐to‐shoot ratios for the 100 μg L−1 treatment, compared to the 10 μg L−1 treatment. The chlorophyll content index of the treated plants was significantly reduced in P. hydropiperoides, compared to the untreated plants on Days 7 and 18. Ludwigia peploides was affected only on the day after exposure, with the chlorophyll fluorescence parameters being significantly less for the 1000 μg L−1 treatment, compared to the 10 μg L−1 treatment. Glyphosate‐treated P. hydropiperoides showed a decreased chlorophyll content and reduced chlorophyll fluorescence parameters. In contrast, L. peploides showed a decrease in the chlorophyll fluorescence parameters but no reduction in its chlorophyll content. In addition to demonstrating the adverse effects of root exposure to glyphosate for the study species, these data help to partially explain the highly invasive and persistent nature of L. peploides in marginal aquatic environments, such as agricultural ditches.
The diet and distribution of Pentacoelum kazukolinda (Kawakatsu & Mitchell, 1984), a maricolan planarian with a freshwater ecology
Authors: Sluys Ronald , Vila‐Farré Miquel , Álvarez‐Presas Marta , Riutort Marta , Kawakatsu Masaharu , Tulp Arnold S.
Published: October 2014

Among the marine triclads or Maricola, the genus Pentacoelum represents one of the few exceptions in that species occur in brackish water or in freshwater. We examined specimens of a maricolan triclad that externally looked remarkably similar to the continental Spanish representatives of freshwater Pentacoelum hispaniense, albeit that these new samples came from habitats in Germany, the Netherlands, Mallorca and Japan. Comprehensive comparative morphological studies revealed that the animals from these populations are identical to a species described earlier from Hawaii, viz. Oahuhawaiiana kazukolinda Kawakatsu & Mitchell, 1984. It is argued that the species now should be called Pentacoelum kazukolinda (Kawakatsu & Mitchell, 1984) comb. nov. Remarkably, Dutch and German specimens of P. kazukolinda almost completely lack any signs of the presence of the lateral gonopore system, being the defining feature of their taxonomic family, the Bdellouridae. The reason for this reduction or even complete absence of this structure remains obscure. Nonetheless, morphological similarities and 18S rDNA sequences strongly suggest that all animals belong to the same species. Analyses of the mitochondrial gene sequences Cox1 and 16SrDNA of the gut content of P. kazukolinda revealed that the flatworm has a preference for different species of gastropods, while in one population annelids were detected. Our study suggests that gastropods may form the food refuge of P. kazukolinda. Circumstantial evidence suggests that the worldwide distribution of P. kazukolinda may result from human‐mediated transport of the aroid Colocasia esculenta and/or the introduced snail Potamopyrgus antipodarum. The use of P. antipodarum as a food resource may have facilitated the spread and establishment of new populations of P. kazukolinda.
Time-Domain Optimal Experimental Design in Human Seated Postural Control Testing
Authors: Cody Priess M. , Choi Jongeun , Radcliffe Clark , Popovich John M. , Cholewicki Jacek , Peter Reeves N.
Published: October 2014

We are developing a series of systems science-based clinical tools that will assist in modeling, diagnosing, and quantifying postural control deficits in human subjects. In line with this goal, we have designed and constructed a seated balance device and associated experimental task for identification of the human seated postural control system. In this work, we present a quadratic programming (QP) technique for optimizing a time-domain experimental input signal for this device. The goal of this optimization is to maximize the information present in the experiment, and therefore its ability to produce accurate estimates of several desired seated postural control parameters. To achieve this, we formulate the problem as a nonconvex QP and attempt to locally maximize a measure (T-optimality condition) of the experiment’s Fisher information matrix (FIM) under several constraints. These constraints include limits on the input amplitude, physiological output magnitude, subject control amplitude, and input signal autocorrelation. Because the autocorrelation constraint takes the form of a quadratic constraint (QC), we replace it with a conservative linear relaxation about a nominal point, which is iteratively updated during the course of optimization. We show that this iterative descent algorithm generates a convergent suboptimal solution that guarantees monotonic nonincreasing of the cost function value while satisfying all constraints during iterations. Finally, we present successful experimental results using an optimized input sequence.