bluuebunny/crossref_metadata_2025 huggingface dataset:
Attractant effect of citral on Platypus koryoensis (Coleoptera: Curculionidae)
Authors: Kim Hyun Kyung , Seo Jin‐Won , Kang Won Jin , Lee Jae Seon , Cho Woo Seong , Seo Sang‐Tae , Kwon Young‐Dae , Kwon Gun Hyung , Kim Gil‐Hah
Published: August 2017

An environmentally friendly control strategy for the ambrosia beetle Platypus koryoensis (Murayama), a vector of oak wilt disease, was investigated using the citral as a pheromone component. To develop an effective attractant trap, a semi‐field experiment (Yeoju) and a field experiment (Gunpo) were performed. Different ratios of four different attractant mixtures (ethanol 100 %, ethanol + citral (90:10, 95:5), ethanol + citral + hexane extract of Quercus mongolica (90:5:5)) were investigated to determine their effects on P. koryoensis. The 95:5 mixture of ethanol + citral had the greatest attractant effect on P. koryoensis. However, other ambrosia beetle species did not exhibit a specific response to citral. Our findings indicate that the pheromone citral was effective at attracting P. koryoensis and that certain concentrations of citral could be used to develop an effective and environmentally friendly control agent.
Ultrastructure structure of antennal sensilla of carabid beetle Carabus elysii Thomson, 1856 (Coleoptera: Carabidae)
Authors: Li Wen‐Bo , Liu Nai‐Yi , Xu Qin , Sun Min , Fang Jie , Wang Shu‐Yan
Published: August 2017

The sensilla type, number and distribution in male and female adults of Carabus elysii Thomson, 1856 (Coleoptera: Carabidae) were studied using scanning electron microscopy. The results showed that there are seven categories and 12 types of sensilla in C. elysii adults: three types of S.Ch, three types of S.T, two types of S.B and one each of B.B, S.Co, S.Ca and S.Cam. There is no difference between male and female in the types of sensilla. Apart from the significant difference in the number and distribution of S.B.2, S.Co and S.Ca between male dorsal and ventral surfaces, there are no significant differences between male and female antennae. In general, the number of sensilla in females is larger than that in males. The results provide a basic reference for future ultrastructure, electrophysiological, and comparative behavioral studies of Carabus species.
Roads to advanced vaccines: influenza case study
Authors: Riese Peggy , Guzmán Carlos A.
Published: August 2017

Vaccines represent a cornerstone to ensure healthy lives and promote well‐being for all at all ages. However, there are many diseases for which vaccines are not available, are relatively ineffective or need to be adapted periodically. Advances in microbial biotechnology will contribute to overcoming these roadblocks by laying the groundwork for improving and creating new approaches for developing better vaccines, as illustrated here in the case of influenza.
The association between P selectin glycoprotein ligand 1 gene variable number of tandem repeats polymorphism and risk of thrombosis in Behçet's disease
Authors: Cosan Fulya , Oku Basar , Gedar Totuk Ozgun M. , Abaci Neslihan , Ustek Duran , Diz Kucukkaya Reyhan , Gul Ahmet
Published: August 2017

Objectives

Behçet's disease (BD) has been recognized as an unclassified type of vasculitis with an accompanying tendency to thrombosis. No disease‐specific pathology has been demonstrated so far to explain the prothrombotic state, and this predisposition is considered to be associated with endothelial activation/dysfunction. P‐selectin glycoprotein ligand‐1 (PSGL‐1) variable number of tandem repeat (VNTR) polymorphism has an impact on the protein length, and heterozygosity affect of the PSGL‐1 to P‐selectin interaction, which has been found to be associated with an increased risk of thrombosis in patients with antiphospholipid syndrome. We aimed to analyze the association of PSGL‐1 gene polymorphism, in a group of BD patients with and without thrombosis.

Methods

The study group consisted of 136 BD patients (112 male, 24 female) with thrombosis, 120 BD patients without thrombosis (54 male, 66 female) during at least 5 years disease course, and 190 healthy controls (103 male, 87 female) All patients fulfilled the International Study Group criteria for classification of BD. Genotyping for the PSGL‐1 gene exon 2 VNTR polymorphism was carried out with the amplification of genomic DNA and running of the polymerase chain reaction product on agarose gel electrophoresis.

Results

The frequency of heterozygous genotypes (AB+AC+BC) was greater in BD patients with thrombosis compared to BD patients without thrombosis (33.1% vs. 20.8%, P = 0.028, odds ratio = 1.85). However, the increased frequency of heterozygous genotypes in BD patients with thrombosis did not reach a statistically significant level compared to healthy controls (33.1% vs. 32.6%).

Conclusions

PSGL‐1 VNTR polymorphism may have limited contribution to the thrombotic tendency in patients with BD.
Mergers with interfirm bundling: a case of pharmaceutical cocktails
Authors: Song Minjae , Nicholson Sean , Lucarelli Claudio
Published: August 2017

Pharmaceutical cocktails often consist of two or more drugs produced by competing firms. The component drugs are often also sold as stand‐alone products. We analyze the effects of a merger between two pharmaceutical firms selling complements for colorectal cancer treatment. In this setting there are two merger effects: the standard upward pricing pressure due to firms internalizing the substitution between the stand‐alone products, and an additional effect where the firms internalize the impact of selling complements and reduce the price of the cocktail product. The net impact of a merger is a modest price increase, or even a price decrease.
Apple's agency model and the role of most‐favored‐nation clauses
Authors: Foros Øystein , Kind Hans Jarle , Shaffer Greg
Published: August 2017

The agency model used by Apple and other digital platforms delegates retail‐pricing decisions to upstream content providers subject to a fixed revenue‐sharing rule. Given competition both upstream and downstream, we consider how, under the agency model, retail prices depend on the firms' revenue‐sharing splits and the degrees to which consumers view the platforms and the goods sold on the platforms to be substitutes. We show that the agency model may not be universally adopted even if adoption would mean higher profits for all firms. Use of most‐favored‐nation clauses in these settings can ensure industry‐wide adoption and increase retail prices.
An offer you can't refuse: early contracting with endogenous threat
Authors: Jullien Bruno , Pouyet Jerome , Sand‐Zantman Wilfried
Published: August 2017

A seller has private information on the future gains from trade with a buyer, but the buyer has the option to invest to produce the good internally. Both the buyer and the seller can efficiently trade ex post under complete information. Despite the lack of information, the buyer sometimes gains by making an early contract offer to the seller. The early contract divides the different types of sellers according to their information, which renders the threat of producing the good in‐house credible and enables the buyer to extract a larger share of the gains from trade. Several extensions are investigated.
The Interrelationships between REIT Capital Structure and Investment
Authors: Alcock Jamie , Steiner Eva
Published: August 2017

We explore the interdependence of investment and financing choices in US listed Real Estate Investment Trusts (REITs) in the period 1973–2011. We find that the investment and financing choices of REITs are interdependent, but they are not made simultaneously. Our results suggest that investment determines leverage, but leverage has no apparent effect on investment decisions. Conversely, the debt‐overhang conflict between shareholders and debt holders that theoretically drives the reverse influence of leverage on investment policy does not appear to filter through to the actual investment choices of REITs. Rather, we find that REIT managers utilize the maturity dimension of capital structure to mitigate potential investment distortions and ensure that investment remains on its value‐maximizing path. We also present novel evidence on the role of investments in driving a wedge between REIT target leverage and actual leverage levels, and on the interplay between investments and leverage adjustments toward the target ratio in explaining REIT capital structure dynamics.
Partitioning beta‐diversity through different pond hydroperiod lengths reveals predominance of nestedness in assemblages of immature odonates
Authors: Pires Mateus Marques , Stenert Cristina , Maltchik Leonardo
Published: August 2017

Patterns of freshwater invertebrate assemblage structure in the transition from permanent to non‐permanent lentic habitats are well described in the literature. However, the effects of small changes in the hydroperiod of non‐permanent ponds on invertebrate assemblage structure remain less studied, especially on β‐diversity. Thus, we tested the effects of different pond hydroperiod lengths on the assemblage structure of immature odonates, in terms of both α‐ and β‐diversity. Small high‐altitude ponds with different hydroperiod lengths (assigned to ‘short’, ‘medium’ and ‘long’ hydroperiods) were sampled in southern Brazil between 2013 and 2014. Based on the hypothesis that shorter hydroperiods filter constituents of lentic fauna, i.e. that long‐living species cannot inhabit shorter‐hydroperiod ponds, we expected to find higher α‐ and β‐diversity in longer hydroperiods, as well as predominance of the nestedness component in β‐diversity. Restricted occurrence of some genera and higher α‐diversity of immature odonate assemblages was detected in long‐hydroperiod ponds. Within‐hydroperiod β‐diversity values did not vary among hydroperiods, because the occasional occurrence of some genera with high dispersal ability of adults in short‐hydroperiod ponds yielded similar values of the β‐diversity among hydroperiods. Partitioning of β‐diversity among hydroperiods revealed a significant higher contribution of the nestedness component rather than turnover. This pattern is explained by the occurrence of some generalist genera across the whole gradient of hydroperiod, as a subset of fauna in longer‐hydroperiod ponds. Thus, our results suggest that reduction in hydroperiod length, if occurring in the future climate change, would favor habitat‐generalist taxa in lentic ecosystems.
Detrital zircon multi‐chronology, provenance, and low‐grade metamorphism of the Cretaceous Shimanto accretionary complex, eastern Shikoku, Southwest Japan: Tectonic evolution in response to igneous activity within a subduction zone
Authors: Hara Hidetoshi , Nakamura Yoshihiro , Hara Kousuke , Kurihara Toshiyuki , Mori Hiroshi , Iwano Hideki , Danhara Tohru , Sakata Shuhei , Hirata Takafumi
Published: August 2017

Detrital zircon multi‐chronology combined with provenance and low‐grade metamorphism analyses enables the reinterpretation of the tectonic evolution of the Cretaceous Shimanto accretionary complex in Southwest Japan. Detrital zircon U–Pb ages and provenance analysis defines the depositional age of trench‐fill turbidites associated with igneous activity in provenance. Periods of low igneous activity are recorded by youngest single grain zircon U–Pb ages (YSG) that approximate or are older than the depositional ages obtained from radiolarian fossil‐bearing mudstone. Periods of intensive igneous activity recorded by youngest cluster U–Pb ages (YC1σ) that correspond to the younger limits of radiolarian ages. The YC1σ U–Pb ages obtained from sandstones within mélange units provide more accurate younger depositional ages than radiolarian ages derived from mudstone. Determining true depositional ages requires a combination of fossil data, detrital zircon ages, and provenance information. Fission‐track ages using zircons estimated YC1σ U–Pb ages are useful for assessing depositional and annealing ages for the low‐grade metamorphosed accretionary complex. These new dating presented here indicates the following tectonic history of the accretionary wedge. Evolution of the Shimanto accretionary complex from the Albian to the Turonian was caused by the subduction of the Izanagi plate, a process that supplied sediments via the erosion of Permian and Triassic to Early Jurassic granitic rocks and the eruption of minor amounts of Early Cretaceous intermediate volcanic rocks. The complex subsequently underwent intensive igneous activity from the Coniacian to the early Paleocene as a result of the subduction of a hot and young oceanic slab, such as the Kula–Pacific plate. Finally, the major out‐of‐sequence thrusts of the Fukase Fault and the Aki Tectonic Line formed after the middle Eocene, and this reactivation of the Shimanto accretionary complex as a result of the subduction of the Pacific plate.
Practice characteristics and service provision rates of dental hygienists in Australia
Authors: Amarasena N , Teusner DN , Brennan DS , Satur J
Published: August 2017

Introduction

Dental hygienists (DHs) have been practising in Australia since the early 1970s.

Objective

This study describes the clinical activity of Australian DHs.

Methods

A questionnaire was mailed to members of two professional associations representing DHs. Practitioner characteristics, employment characteristics and clinical activity on a self‐reported typical practice day were collected. The proportion of each service item of all services provided was estimated. Associations between practice characteristics and service provision were assessed by log‐binomial regression models.

Results

Adjusted response rate was 60.6%. Of the DHs included in analysis (n=341), 80% were employed in general practice, and nearly all (96%) worked in the private sector. About half (53.7%) of all service provided were preventive services, and one‐fourth (23.9%) were diagnostic. Service provision varied by practice and practitioner characteristics, with the largest variations observed by practice type. Unadjusted analysis showed that general practice DHs provided a higher mean number of periodontal instrumentation and coronal polishing (0.92 vs 0.26), fluoride applications (0.64 vs 0.08), oral examinations (0.51 vs 0.22) and intraoral radiographs (0.33 vs 0.07) per patient visit and a lower mean number of impressions (0.05 vs 0.17) and orthodontic services (0.02 vs 0.59) than specialist practice DHs. In adjusted analysis, rates of periodontal services also significantly varied by practice type; other associations persisted.

Conclusion

Service provision of DHs varied by practice type. Practice activity was dominated by provision of preventive services while provision of periodontal treatments, fissure sealants and oral examinations was relatively limited indicating areas in which DHs are possibly underutilized.
The meaning of work among immigrants living in poverty in Israel: Replanting roots of belonging
Authors: Sigad Laura I. , Eisikovits Zvi , Strier Roni , Buchbinder Eli
Published: August 2017

The global financial crisis has increased the number of working immigrants living in poverty around the world. This article presents and analyses the interaction of work, immigration and poverty among working immigrants in Israel. Methodologically, this study has combined hermeneutic phenomenological and social constructivist approaches and in so doing has aimed to describe the realities of immigrants living and working in poverty. Presenting both men's and women's perspectives, we found that immigrants who work and live in poverty attribute crucial significance to work, which serves as a primary route of integration into the new culture as well as a means of coping with both the uprootedness caused by immigration and the difficulties of living in poverty. However, immigrants’ construction of work as the sole conduit for integration leaves them particularly vulnerable to discriminatory workplace practices.
Cross‐Sectional and Time Series Momentum Returns and Market States
Authors: Cheema Muhammad A. , Nartea Gilbert V. , Man Yimei
Published: August 2017

Recent evidence on momentum returns shows that the time series (TS) strategy outperforms the cross‐sectional (CS) strategy. We present new evidence that this happens only when the market continues in the same state, up or down. In fact, we find that the TS strategy underperforms the CS strategy when the market transitions to a different state. Our results also show that the difference in momentum returns between TS and CS strategies is related to both the net long and net short positions of the TS strategy.
A quantitative evaluation of physical and digital approaches to centre of mass estimation
Authors: Macaulay Sophie , Hutchinson John R. , Bates Karl T.
Published: August 2017

Centre of mass is a fundamental anatomical and biomechanical parameter. Knowledge of centre of mass is essential to inform studies investigating locomotion and other behaviours, through its implications for segment movements, and on whole body factors such as posture. Previous studies have estimated centre of mass position for a range of organisms, using various methodologies. However, few studies assess the accuracy of the methods that they employ, and often provide only brief details on their methodologies. As such, no rigorous, detailed comparisons of accuracy and repeatability within and between methods currently exist. This paper therefore seeks to apply three methods common in the literature (suspension, scales and digital modelling) to three ‘calibration objects’ in the form of bricks, as well as three birds to determine centre of mass position. Application to bricks enables conclusions to be drawn on the absolute accuracy of each method, in addition to comparing these results to assess the relative value of these methodologies. Application to birds provided insights into the logistical challenges of applying these methods to biological specimens. For bricks, we found that, provided appropriate repeats were conducted, the scales method yielded the most accurate predictions of centre of mass (within 1.49 mm), closely followed by digital modelling (within 2.39 mm), with results from suspension being the most distant (within 38.5 mm). Scales and digital methods both also displayed low variability between centre of mass estimates, suggesting they can accurately and consistently predict centre of mass position. Our suspension method resulted not only in high margins of error, but also substantial variability, highlighting problems with this method.
Men wielding the plough: Changing patterns of production and reproduction among the Balanta of Guinea‐Bissau
Authors: Temudo Marina Padrão
Published: August 2017

This paper is centred on the fast‐track changes occurring among the Balanta of Guinea‐Bissau—at present, the only ethnic group in West Africa still able to produce a mangrove swamp rice surplus with a manual plough—in their traditionally intensive farming system and their social organization, and on the consequences that these changes have had for gender relations, especially with regard to married women's spatial mobility, sexual and economic independence, and access to land, labour, and capital. In doing so, the paper contributes to old debates about the relationship between means of production and gendered power dynamics in contexts where African societies based on domestic modes of production progressively embrace the market economy. The Balanta case offers a new layer of complexity to this debate due to their long‐term resistance to westernization and market integration, their particular conjugal relations, and the paradoxical way in which women have been losing their traditional rights.
Transdifferentiation of myoblasts into osteoblasts – possible use for bone therapy
Authors: Lin Daphne P L , Carnagarin Revathy , Dharmarajan Arun , Dass Crispin R
Published: August 2017

Objectives

Transdifferentiation is defined as the conversion of one cell type to another and is an ever-expanding field with a growing number of cells found to be capable of such a process. To date, the fact remains that there are limited treatment options for fracture healing, osteoporosis and bone repair post-destruction by bone tumours. Hence, this review focuses on the transdifferentiation of myoblast to osteoblast as a means to further understand the transdifferentiation process and to investigate a potential therapeutic option if successful.

Key findings

The potent osteoinductive effects of the bone morphogenetic protein-2 are largely implicated in the transdifferentiation of myoblast to osteoblast. Bone morphogenetic protein-2-induced activation of the Smad1 protein ultimately results in JunB synthesis, the first transcriptional step in myoblast dedifferentiation. The upregulation of the activating protein-1 binding activity triggers the transcription of the runt-related transcription factor 2 gene, a transcription factor that plays a major role in osteoblast differentiation.

This potential transdifferentiation treatment may be utilised for dental implants, fracture healing, osteoporosis and bone repair post-destruction by bone tumours.
Floating solid cellulose nanofibre nanofoams for sustained release of the poorly soluble model drug furosemide
Authors: Svagan Anna Justina , Müllertz Anette , Löbmann Korbinian
Published: August 2017

Objectives

This study aimed to prepare a furosemide-loaded sustained release cellulose nanofibre (CNF)-based nanofoams with buoyancy.

Methods

Dry foams consisting of CNF and the model drug furosemide at concentrations of 21% and 50% (w/w) have been prepared by simply foaming a CNF-drug suspension followed by drying. The resulting foams were characterized towards their morphology, solid state properties and dissolution kinetics.

Key findings

Solid state analysis of the resulting drug-loaded foams revealed that the drug was present as an amorphous sodium furosemide salt and in form of furosemide form I crystals embedded in the CNF foam cell walls. The foams could easily be shaped and were flexible, and during the drug release study, the foam pieces remained intact and were floating on the surface due to their positive buoyancy. Both foams showed a sustained furosemide release compared to a marketed tablet. It was found that the extent of sustained release from both foams was dependent on the drug loading, the dimension of the foam piece, as well as the solid state of the drug.

Conclusions

Furosemide-loaded CNF-based foams with sustained release and buoyancy have been successfully prepared in a simple casting and drying procedure.
Stimulation of human osteoblast cells (MG63) proliferation using decanoic acid and isopropyl amine fractions of Wattakaka volubilis leaves
Authors: Venugopal Elakkiya , Ramadoss Govindarajan , Krishnan Kannan , Eranezhath Sujith Subash , Bhattacharyya Amitava , Rajendran Selvakumar
Published: August 2017

Objectives

This study was carried out to investigate the impact of various isolated phytochemical components present in the Wattakaka volubilis leaves for the growth and proliferation of human osteoblast like cells (MG63).

Key findings

Ethyl acetate was found to be the best solvent for potential extraction of phytocompounds. Further, the MTT assay was carried out to deduce the viability of 44 isolated phytochemicals. Ten phytochemical fractions found to increase the cell growth were subjected to statistical tool namely Plackett–Burman and Central composite design to screen the optimum phytochemical fraction and its dosage. The active phytochemical constituents were analysed and identified as hexadeconoic acid, octadeconoic acid, N,N-diisopropyl(2,2,3,3,3-pentafluoropropyl)amine using GC-MS and HPLC techniques. The impact of optimized concentration was assessed on osteoblast cells. The maximum % cell viability, % DNA and collagen content were found to be 164.44, 159.32 and 3.81, respectively.

Conclusions

The results confirmed that the optimized fraction containing decanoic acid and isopropyl amine at particular concentration stimulated the proliferation of human osteoblast (MG63) cells. Hence, the optimized concentration of this compound from W. volubilis may used for treatment of bone related injuries externally.
Preventing childhood obesity: Early‐life messages from epidemiology
Authors: Robinson S. M.
Published: August 2017

The high rates of overweight and obesity, currently seen in young children, underline the urgent need for preventive strategies in early life, before excess weight is gained. However, alongside such practical considerations, a body of epidemiological evidence now links experience in fetal and early postnatal life to an individual's later risk of obesity – pointing to the importance and role of ‘developmental influences’, such as maternal obesity, excess gestational weight gain and short duration of breastfeeding, in the aetiology of childhood obesity. Differences in early experience are linked to lifelong differences in predisposition to gain weight and, as the associated differences in obesity risk are large, real benefits could be achieved by early intervention. Such messages, regarding the need for efforts to address these early influences to prevent obesity, are now embedded in national and international health policy. Whilst successful prevention initiatives are needed early in life, the most effective strategies may need to be focused even earlier in the life course, in the period before conception. Although the challenges of changing behaviour are considerable, such changes have the potential to impact both on the health of future mothers and future generations.
Dietary energy density: Applying behavioural science to weight management
Authors: Rolls B. J.
Published: August 2017

Studies conducted by behavioural scientists show that the energy density (kcal/g) of food provides effective guidance for healthy food choices to control intake and promote satiety. Energy density depends upon a number of dietary components, especially water (0 kcal/g) and fat (9 kcal/g). Increasing the proportion of water or water‐rich ingredients, such as vegetables or fruit, lowers a food's energy density. A number of studies show that when the energy density of the diet is reduced, both adults and children spontaneously decrease their ad libitum energy intake. Other studies show that consuming a large volume of a low‐energy‐dense food, such as soup, salad or fruit, as a first course preload can enhance satiety and reduce overall energy intake at a meal. Current evidence suggests that energy density influences intake through a complex interplay of cognitive, sensory, gastrointestinal, hormonal and neural influences. Other studies that focus on practical applications show how the strategic incorporation of foods lower in energy density into the diet allows people to eat satisfying portions while improving dietary patterns. This review discusses studies that have led to greater understanding of the importance of energy density for food intake regulation and weight management.
Saturated fats, dairy foods and health: A curious paradox?
Authors: Givens D. I.
Published: August 2017

Cardiovascular diseases (CVD) remain a major cause of death and morbidity worldwide. Dietary guidelines aim to restrict the intake of saturated fatty acids (SFA) as they are regarded as an important risk factor for CVD due to their association with increased blood cholesterol. As dairy foods are major contributors of dietary SFA, there have been guidelines to reduce consumption of these foods. However, it is now generally accepted that the effects of reducing intake of SFA are dependent on what replaces them in the diet. Reduced CVD risk has been associated with replacement of SFA with cis‐polyunsaturated fatty acids (cis‐PUFA) and/or cis‐monounsaturated fatty acids (cis‐MUFA), with replacement by carbohydrate leading to no reduction or even increased CVD risk. Most studies on the effect of diet/food on CVD risk have used total cholesterol (TC) and/or low‐density lipoprotein cholesterol (LDL‐C) in blood as the marker(s) of risk. However, because of potentially attenuating effects of dairy foods (e.g. effect of protein on blood lipids and blood pressure; food matrix effects on fat bioavailability), a wider range of markers is needed to more fully evaluate disease risk. Nevertheless, whilst prospective evidence shows no increase in CVD risk from high dairy consumption, it is still unclear whether replacing a proportion of SFA in dairy fat with cis‐MUFA will lead to reduced CVD risk. The relatively few randomised controlled trials that have examined this using TC/LDL‐C as risk markers give some indications of reduced CVD risk from consumption of milk and dairy products with modified fatty acid composition, compared with those of normal milk fat composition. The results of ongoing studies will add valuable new evidence on this issue.
A Research on Mathematical Thinking Skills: Mathematical Thinking Skills of Athletes in Individual and Team Sports
Authors: Onal Halil , Inan Mehmet , Bozkurt Sinan
Published: August 2017

The aim of this research is to examine the mathematical thinking skills of licensed athletes engaged in individual and team sports. The research is designed as a survey model. The sample of the research is composed of 59 female and 170 male licensed athletes (n = 229) and (aged 14 to 52) licensed who do the sports of shooting, billiards, archery, tennis, basketball, football, volleyball in various clubs in Turkey. The "Mathematical Thinking Scale" developed by Ersoy (2012) has been employed in the research. Individual sports athletes are more likely to have higher mathematical thinking scores than team athletes. In sports types; those who play billiards and archery have higher scores of mathematical thinking skills compared to other sports types. According to the type of sports the lowest scores of thinking skills were obtained by basketball players. These differences are valid for higher-level thinking tendencies, reasoning, mathematical thinking skills and problem-solving skills, which are sub-dimensions of the mathematical thinking scale.
Loss of SPDEF and gain of TGFBI activity after androgen deprivation therapy promote EMT and bone metastasis of prostate cancer
Authors: Chen Wei-Yu , Tsai Yuan-Chin , Yeh Hsiu-Lien , Suau Florent , Jiang Kuo-Ching , Shao Ai-Ning , Huang Jiaoti , Liu Yen-Nien
Published: August 2017

Loss of a TGFβ signaling repressor by androgen deprivation therapy shows how a common treatment for primary prostate cancer may promote metastasis.
New connections: From understanding to targeting S1P
1
on endothelial cells
Authors: Wong Wei
Published: August 2017

Understanding how the S1P receptor S1P
1
is specifically activated in endothelial cells may lead to drugs with fewer side effects.
Papers of note in
Science
357
(6351)
Authors: Ferrarelli Leslie K.
Published: August 2017

This week’s articles describe a second messenger that coordinates CRISPR-Cas immunity in bacteria and show how metabolism mediates protective crosstalk between the gut and resident microbes.
Using Population Pharmacokinetic Modeling and Monte Carlo Simulations To Determine whether Standard Doses of Piperacillin in Piperacillin-Tazobactam Regimens Are Adequate for the Management of Febrile Neutropenia
Authors: Sime Fekade Bruck , Hahn Uwe , Warner Morgyn S. , Tiong Ing Soo , Roberts Michael S. , Lipman Jeffrey , Peake Sandra L. , Roberts Jason A.
Published: August 2017

Changes in the pharmacokinetics of piperacillin in febrile neutropenic patients have been reported to result in suboptimal exposures. This study aimed to develop a population pharmacokinetic model for piperacillin and perform dosing simulation to describe optimal dosing regimens for hematological malignancy patients with febrile neutropenia. Concentration-time data were obtained from previous prospective observational pharmacokinetic and interventional therapeutic drug monitoring studies. Nonparametric population pharmacokinetic analysis and Monte Carlo dosing simulations were performed with the Pmetrics package for R. A two-compartment model, with between-subject variability for clearance (CL), adequately described the data from 37 patients (21 males, age of 59 ± 12 years [means ± standard deviations] and weight of 77 ± 16 kg). Parameter estimates were CL of 18.0 ± 4.8 liters/h, volume of distribution of the central compartment of 14.3 ± 7.3 liters, rate constant for piperacillin distribution from the central to peripheral compartment of 1.40 ± 1.35 h
−1
, and rate constant for piperacillin distribution from the peripheral to central compartment of 4.99 ± 7.81 h
−1
. High creatinine clearance (CL
CR
) was associated with reduced probability of target attainment (PTA). Extended and continuous infusion regimens achieved a high PTA of >90% for an unbound concentration of piperacillin remaining above the MIC (
fT
>MIC
) of 50%. Only continuous regimens achieved >90% PTA for 100%
fT
>MIC
when CL
CR
was high. The cumulative fraction of response (FTA, for fractional target attainment) was suboptimal (<85%) for conventional regimens for both empirical and directed therapy considering 50% and 100%
fT
>MIC
. FTA was maximized with prolonged infusions. Overall, changes in piperacillin pharmacokinetics and the consequences on therapeutic dosing requirements appear similar to those observed in intensive care patients. Guidelines should address the altered dosing needs of febrile neutropenic patients exhibiting high CL
CR
or with known/presumed infections from high-MIC bacteria.
Original Chemical Series of Pyrimidine Biosynthesis Inhibitors That Boost the Antiviral Interferon Response
Authors: Lucas-Hourani Marianne , Dauzonne Daniel , Munier-Lehmann Hélène , Khiar Samira , Nisole Sébastien , Dairou Julien , Helynck Olivier , Afonso Philippe V. , Tangy Frédéric , Vidalain Pierre-Olivier
Published: August 2017

De novopyrimidine biosynthesis is a key metabolic pathway involved in multiple biosynthetic processes. Here, we identified an original series of 3-(1H-indol-3-yl)-2,3-dihydro-4H-furo[3,2-c]chromen-4-one derivatives as a new class of pyrimidine biosynthesis inhibitors formed by two edge-fused polycyclic moieties. We show that identified compounds exhibit broad-spectrum antiviral activity and immunostimulatory properties, in line with recent reports linkingde novopyrimidine biosynthesis with innate defense mechanisms against viruses. Most importantly, we establish that pyrimidine deprivation can amplify the production of both type I and type III interferons by cells stimulated with retinoic acid-inducible gene 1 (RIG-I) ligands. Altogether, our results further expand the current panel of pyrimidine biosynthesis inhibitors and illustrate how the production of antiviral interferons is tightly coupled to this metabolic pathway. Functional and structural similarities between this new chemical series and dicoumarol, which was reported before to inhibit pyrimidine biosynthesis at the dihydroorotate dehydrogenase (DHODH) step, are discussed.
24-Hour Pharmacokinetic Relationships for Vancomycin and Novel Urinary Biomarkers of Acute Kidney Injury
Authors: O'Donnell J. Nicholas , Rhodes Nathaniel J. , Lodise Thomas P. , Prozialeck Walter C. , Miglis Cristina M. , Joshi Medha D. , Venkatesan Natarajan , Pais Gwendolyn , Cluff Cameron , Lamar Peter C. , Briyal Seema , Day John Z. , Gulati Anil , Scheetz Marc H.
Published: August 2017

Vancomycin has been associated with acute kidney injury in preclinical and clinical settings; however, the precise exposure profiles associated with vancomycin-induced acute kidney injury have not been defined. We sought to determine pharmacokinetic/pharmacodynamics indices associated with the development of acute kidney injury using sensitive urinary biomarkers. Male Sprague-Dawley rats received clinical-grade vancomycin or normal saline as an intraperitoneal injection. Total daily doses between 0 and 400 mg/kg of body weight were administered as a single dose or 2 divided doses over a 24-h period. At least five rats were utilized for each dosing protocol. A maximum of 8 plasma samples per rat were obtained, and urine was collected over the 24-h period. Kidney injury molecule-1 (KIM-1), clusterin, osteopontin, cystatin C, and neutrophil gelatinase-associated lipocalin levels were determined using Milliplex multianalyte profiling rat kidney panels. Vancomycin plasma concentrations were determined via a validated high-performance liquid chromatography methodology. Pharmacokinetic analyses were conducted using the Pmetrics package for R. Bayesian maximal
a posteriori
concentrations were generated and utilized to calculate the 24-h area under the concentration-time curve (AUC), the maximum concentration (
C
max
), and the minimum concentration. Spearman's rank correlation coefficient (

r
s

) was used to assess the correlations between exposure parameters, biomarkers, and histopathological damage. Forty-seven rats contributed pharmacokinetic and toxicodynamic data. KIM-1 was the only urinary biomarker that correlated with both composite histopathological damage (

r
s

= 0.348,
P
= 0.017) and proximal tubule damage (

r
s

= 0.342,
P
= 0.019). The vancomycin AUC and
C
max
were most predictive of increases in KIM-1 levels (

r
s

= 0.438 and
P
= 0.002 for AUC and

r
s

= 0.451 and
P
= 0.002 for
C
max
). Novel urinary biomarkers demonstrate that kidney injury can occur within 24 h of vancomycin exposure as a function of either AUC or
C
max
.
Amplification of Antimicrobial Resistance in Gut Flora of Patients Treated with Ceftriaxone
Authors: Meletiadis J. , Turlej-Rogacka A. , Lerner A. , Adler A. , Tacconelli E. , Mouton J. W.
Published: August 2017

Although antibacterial therapy has an impact on human intestinal flora and the emergence of resistant bacteria, its role in the amplification of antimicrobial resistance and the quantitative exposure-effect relationship is not clear. An observational prospective study was conducted to determine whether and how ceftriaxone exposure is related to amplification of resistance in non-intensive care unit (non-ICU) patients. Serial stool samples from 122 extended-spectrum β-lactamase-positive (ESBL
+
) hospitalized patients were analyzed by quantitative real-time PCR to quantify the resistant gene
bla
CTX-M
. Drug exposure was calculated for each patient by using a population pharmacokinetic model. Multi- and univariate regression and classification regression tree (CART) analyses were used to explore relationships between measures of exposure and amplification of
bla
CTX-M
genes. Amplification of
bla
CTX-M
was observed in 0% (0/11) of patients with no treatment and 33% (20/61) of patients treated with ceftriaxone. Stepwise regression analysis showed a significant association between amplification of
bla
CTX-M
and the plasma area under the concentration-time curve from 0 to 24 h for the unbound fraction of the drug (
f
AUC
0–24
), the maximum concentration of drug in serum for the unbound fraction of the drug (
fC
max
), and the duration of ceftriaxone therapy. Using CART analysis, amplification of
bla
CTX-M
was observed in 11/16 (69%) patients treated for >14 days and in 9/40 (23%) patients treated for ≤14 days (
P
= 0.0019). In the latter group, amplification was observed in 5/7 (71%) patients with an
f
AUC
0–24
of ≥222 mg · h/liter and in 4/33 (12%) patients with lower drug exposures (
P
= 0.0033). A similar association was found for an
fC
max
of ≥30 mg/liter (63% versus 13%,
P
= 0.0079). A significant association was found between the amplification of
bla
CTX-M
resistance genes and exposure to ceftriaxone. Both duration of treatment and degree of ceftriaxone exposure have a significant impact on the amplification of resistance genes. (The project described in this paper has been registered at ClinicalTrials.gov under identifier NCT01208519.)
Inhibition of Calcineurin or IMP Dehydrogenase Exerts Moderate to Potent Antiviral Activity against Norovirus Replication
Authors: Dang Wen , Yin Yuebang , Wang Yijin , Wang Wenshi , Su Junhong , Sprengers Dave , van der Laan Luc J. W. , Felczak Krzysztof , Pankiewicz Krzysztof W. , Chang Kyeong-Ok , Koopmans Marion P. G. , Metselaar Herold J. , Peppelenbosch Maikel P. , Pan Qiuwei
Published: August 2017

Norovirus is a major cause of acute gastroenteritis worldwide and has emerged as an important issue of chronic infection in transplantation patients. Since no approved antiviral is available, we evaluated the effects of different immunosuppressants and ribavirin on norovirus and explored their mechanisms of action by using a human norovirus (HuNV) replicon-harboring model and a surrogate murine norovirus (MNV) infectious model. The roles of the corresponding drug targets were investigated by gain- or loss-of-function approaches. We found that the calcineurin inhibitors cyclosporine (CsA) and tacrolimus (FK506) moderately inhibited HuNV replication. Gene silencing of their cellular targets, cyclophilin A, FKBP12, and calcineurin, significantly inhibited HuNV replication. A low concentration, therapeutically speaking, of mycophenolic acid (MPA), an uncompetitive IMP dehydrogenase (IMPDH) inhibitor, potently and rapidly inhibited norovirus replication and ultimately cleared HuNV replicons without inducible resistance following long-term drug exposure. Knockdown of the MPA cellular targets IMPDH1 and IMPDH2 suppressed HuNV replication. Consistent with the nucleotide-synthesizing function of IMPDH, exogenous guanosine counteracted the antinorovirus effects of MPA. Furthermore, the competitive IMPDH inhibitor ribavirin efficiently inhibited norovirus and resulted in an additive effect when combined with immunosuppressants. The results from this study demonstrate that calcineurin phosphatase activity and IMPDH guanine synthase activity are crucial in sustaining norovirus infection; thus, they can be therapeutically targeted. Our results suggest that MPA shall be preferentially considered immunosuppressive medication for transplantation patients at risk of norovirus infection, whereas ribavirin represents as a potential antiviral for both immunocompromised and immunocompetent patients with norovirus gastroenteritis.
Phase 2 Randomized Trial of the Safety and Efficacy of MHAA4549A, a Broadly Neutralizing Monoclonal Antibody, in a Human Influenza A Virus Challenge Model
Authors: McBride Jacqueline M. , Lim Jeremy J. , Burgess Tracy , Deng Rong , Derby Michael A. , Maia Mauricio , Horn Priscilla , Siddiqui Omer , Sheinson Daniel , Chen-Harris Haiyin , Newton Elizabeth M. , Fillos Dimitri , Nazzal Denise , Rosenberger Carrie M. , Ohlson Maikke B. , Lambkin-Williams Rob , Fathi Hosnieh , Harris Jeffrey M. , Tavel Jorge A.
Published: August 2017

MHAA4549A, a human monoclonal antibody targeting the hemagglutinin stalk region of influenza A virus (IAV), is being developed as a therapeutic for patients hospitalized with severe IAV infection. The safety and efficacy of MHAA4549A were assessed in a randomized, double-blind, placebo-controlled, dose-ranging study in a human IAV challenge model. One hundred healthy volunteers were inoculated with A/Wisconsin/67/2005 (H3N2) IAV and, 24 to 36 h later, administered a single intravenous dose of either placebo, MHAA4549A (400, 1,200, or 3,600 mg), or a standard oral dose of oseltamivir. Subjects were assessed for safety, pharmacokinetics (PK), and immunogenicity. The intent-to-treat-infected (ITTI) population was assessed for changes in viral load, influenza symptoms, and inflammatory biomarkers. MHAA4549A was well tolerated in all IAV challenge subjects. The 3,600-mg dose of MHAA4549A significantly reduced the viral burden relative to that of the placebo as determined by the area under the curve (AUC) of nasopharyngeal virus infection, quantified using quantitative PCR (98%) and 50% tissue culture infective dose (TCID50) (100%) assays. Peak viral load, duration of viral shedding, influenza symptom scores, mucus weight, and inflammatory biomarkers were also reduced. Serum PK was linear with a half-life of ∼23 days. No MHAA4549A-treated subjects developed anti-drug antibodies. In conclusion, MHAA4549A was well tolerated and demonstrated statistically significant and substantial antiviral activity in an IAV challenge model. (This study has been registered at ClinicalTrials.gov under identifier NCT01980966.)
Activity of the β-Lactamase Inhibitor LN-1-255 against Carbapenem-Hydrolyzing Class D β-Lactamases from Acinetobacter baumannii
Authors: Vázquez-Ucha Juan Carlos , Maneiro María , Martínez-Guitián Marta , Buynak John , Bethel Christopher R. , Bonomo Robert A. , Bou Germán , Poza Margarita , González-Bello Concepción , Beceiro Alejandro
Published: August 2017

The number of infections caused by Gram-negative pathogens carrying carbapenemases is increasing, and the group of carbapenem-hydrolyzing class D β-lactamases (CHDLs) is especially problematic. Several clinically important CHDLs have been identified in
Acinetobacter baumannii
, including OXA-23, OXA-24/40, OXA-58, OXA-143, OXA-235, and the chromosomally encoded OXA-51. The selection and dissemination of carbapenem-resistant
A. baumannii
strains constitutes a serious global threat. Carbapenems have been successfully utilized as last-resort antibiotics for the treatment of multidrug-resistant
A. baumannii
infections. However, the spread of OXA carbapenemases is compromising the continued use of these antimicrobials. In response to this clinical issue, it is necessary and urgent to design and develop new specific inhibitors with efficacy against these enzymes. The aim of this work was to characterize the inhibitory activity of LN-1-255 (a 6-alkylidene-2-substituted penicillin sulfone) and compare it to that of two established inhibitors (avibactam and tazobactam) against the most relevant enzymes of each group of class D carbapenemases in
A. baumannii
. The β-lactamase inhibitor LN-1-255 demonstrated excellent microbiological synergy and inhibition kinetics parameters against all tested CHDLs and a significantly higher activity than tazobactam and avibactam. A combination of carbapenems and LN-1-255 was effective against
A. baumannii
class D carbapenemases. Docking assays confirmed the affinity of LN-1-255 for the active site of these enzymes. LN-1-255 represents a potential new β-lactamase inhibitor that may have a significant role in eradicating infections caused by
A. baumannii
isolates carrying CHDLs.