bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-glandular trichomes ofSolanum carolinensedeter feeding byManduca sextacaterpillars and cause damage to the gut peritrophic matrix
Authors: Kariyat Rupesh R. , Smith Jason D. , Stephenson Andrew G. , De Moraes Consuelo M. , Mescher Mark C.
Published: February 2017

Plant trichomes constitute a first line of defence against insect herbivores. The pre- and post-ingestive defensive functions of glandular trichomes are well documented and include direct toxicity, adhesion, antinutrition and defence gene induction. By contrast, the defensive functions of non-glandular trichomes are less well characterized, although these structures are thought to serve as physical barriers that impede herbivore feeding and movement. We experimentally varied the density of stellate non-glandular trichomes in several ways to explore their pre- and post-ingestive effects on herbivores. Larvae ofManduca sexta(Sphingidae) initiated feeding faster and gained more weight onSolanum carolinense(Solanaceae) leaves having lower trichome densities (or experimentally removed trichomes) than on leaves having higher trichome densities. Adding trichomes to artificial diet also deterred feeding and adversely affected caterpillar growth relative to controls. Scanning electron and light microscopy revealed that the ingestion of stellate trichomes byM. sextacaterpillars caused extensive damage to the peritrophic membrane, a gut lining that is essential to digestion and pathogen isolation. These findings suggest that, in addition to acting as a physical barrier to deter feeding, trichomes can inhibit caterpillar growth and development via post-ingestive effects.
Shape matters: animal colour patterns as signals of individual quality
Authors: Pérez-Rodríguez Lorenzo , Jovani Roger , Stevens Martin
Published: February 2017

Colour patterns (e.g. irregular, spotted or barred forms) are widespread in the animal kingdom, yet their potential role as signals of quality has been mostly neglected. However, a review of the published literature reveals that pattern itself (irrespective of its size or colour intensity) is a promising signal of individual quality across species of many different taxa. We propose at least four main pathways whereby patterns may reliably reflect individual quality: (i) as conventional signals of status, (ii) as indices of developmental homeostasis, (iii) by amplifying cues of somatic integrity and (iv) by amplifying individual investment in maintenance activities. Methodological constraints have traditionally hampered research on the signalling potential of colour patterns. To overcome this, we report a series of tools (e.g. colour adjacency and pattern regularity analyses, Fourier and granularity approaches, fractal geometry, geometric morphometrics) that allow objective quantification of pattern variability. We discuss how information provided by these methods should consider the visual system of the model species and behavioural responses to pattern metrics, in order to allow biologically meaningful conclusions. Finally, we propose future challenges in this research area that will require a multidisciplinary approach, bringing together inputs from genetics, physiology, behavioural ecology and evolutionary-developmental biology.
High monetary reward rates and caloric rewards decrease temporal persistence
Authors: Fung Bowen J. , Bode Stefan , Murawski Carsten
Published: February 2017

Temporal persistence refers to an individual's capacity to wait for future rewards, while forgoing possible alternatives. This requires a trade-off between the potential value of delayed rewards and opportunity costs, and is relevant to many real-world decisions, such as dieting. Theoretical models have previously suggested that high monetary reward rates, or positive energy balance, may result in decreased temporal persistence. In our study, 50 fasted participants engaged in a temporal persistence task, incentivised with monetary rewards. In alternating blocks of this task, rewards were delivered at delays drawn randomly from distributions with either a lower or higher maximum reward rate. During some blocks participants received either a caloric drink or water. We used survival analysis to estimate participants' probability of quitting conditional on the delay distribution and the consumed liquid. Participants had a higher probability of quitting in blocks with the higher reward rate. Furthermore, participants who consumed the caloric drink had a higher probability of quitting than those who consumed water. Our results support the predictions from the theoretical models, and importantly, suggest that both higher monetary reward rates and physiologically relevant rewards can decrease temporal persistence, which is a crucial determinant for survival in many species.
Biological activities in Aronia melanocarpa depending on drying methods
Authors: Lee Seul , Moon Hey-Kyung , Lee Su-Won , Moon Jae-Nam , Kim Jong-Kuk
Published: February 2017

To investigate biological activities in Aronia melanocarpa various drying methods were employed such as vacuum freeze drying, hot air drying and cold air drying. DPPH radical scavenging activity and ABTS radical scavenging activity of vacuum freeze dried Aronia melanocarpa was higher than hot and cold air dried Aronia melanocarpa. Vacuum freeze drying method showed the greatest contents of total phenol (15.34 g GAE/100 g), flavonoid (3.10 g GE/100 g) and tannin (2.46 g TE/100 g). Total anthocyanin content decreased to 163.52 mg C3G/100 g and 50.15 mg C3G/100 g for hot and cold air drying, respectively. Vacuum freeze-dried method increased the total anthocyanin content (743.09 mg C3G/100 g) when compared with fresh Aronia melanocarpa (163.52 mg C3G/100 g). Total proanthocyanidin content of vacuum freeze dried Aronia melanocarpa has increased to 6.21 g CE/100 g more than eight times compared with fresh Aronia melanocarpa (0.71 g CE/100 g). Chlorogenic acid and neochlorogenic acid content of vacuum freeze dried Aronia melanocarpa were higher than hot air dried and cold air dried Aronia melanocarpa, increasing about three times compared with fresh Aronia melanocarpa. These results suggested that vacuum freeze drying is optimal drying method to enhance biological activities in Aronia melanocarpa.
GCalignR: An R package for aligning Gas-Chromatography data
Authors: Ottensmann Meinolf , Stoffel Martin A. , Nichols Hazel J. , Hoffman Joseph I.
Published: February 2017

Chemical cues are arguably the most fundamental means of animal communication and play an important role in mate choice and kin recognition. Consequently, gas chromatography (GC) in combination with either mass spectrometry (MS) or flame ionisation detection (FID) are commonly used to characterise complex chemical samples. Both GC-FID and GC-MS generate chromatograms comprising peaks that are separated according to their retention times and which represent different substances. Across chromatograms of different samples, homologous substances are expected to elute at similar retention times. However, random and often unavoidable experimental variation introduces noise, making the alignment of homologous peaks challenging, particularly with GC-FID data where mass spectral data are lacking. Here we presentGCalignR, a user-friendly R package for aligning GC-FID data based on retention times. The package also implements dynamic visualisations to facilitate inspection and fine-tuning of the resulting alignments, and can be integrated within a broader workflow in R to facilitate downstream multivariate analyses. We demonstrate an example workflow using empirical data from Antarctic fur seals and explore the impact of user-defined parameter values by calculating alignment error rates for multiple datasets. The resulting alignments had low error rates for most of the explored parameter space and we could also show thatGCalignRperformed equally well or better than other available software. We hope thatGCalignRwill help to simplify the processing of chemical datasets and improve the standardization and reproducibility of chemical analyses in studies of animal chemical communication and related fields.
The Pax9/Wnt pathway regulates secondary palate formation in mice
Authors: Jia Shihai , Zhou Jing , Fanelli Christopher , Wee Yinshen , Bonds John , Schneider Pascal , Mues Gabriele , D’Souza Rena N.
Published: February 2017

Clefts of the palate and/or lip arise in about 1/700 human live births and are caused by multiple genetic and environmental factors. Studies of mouse knockout models of cleft palate have improved our understanding of the molecular control of palatogenesis. While it is known that Pax9 regulates palatogenesis through Bmp, Fgf and Shh signaling, there is still much to learn about its precise relationship with other pathways. Here we show that alterations of Wnt expression and decreased Wnt activity inPax9-/-palatal shelves are a result of Pax9’s ability to directly bind and repress the promoters ofDkk1andDkk2,proteins that antagonize Wnt signaling. The delivery of small-molecule Dkk inhibitors (Wnt agonists) into the tail-veins of pregnantPax9+/-mice from E10.5 to E14.5 restored Wnt signaling, promoted cell proliferation, bone formation and restored the fusion of palatal shelves inPax9-/-embryos. In contrast, other organ defects inPax9mutants were not corrected. These data uncover a unique molecular relationship betweenPax9and Wnt genes in palatogenesis and offer a new approach for treating cleft palates in humans.

Summary Statement

These studies demonstrate that the Pax9/Wnt genes regulate murine palatogenesis. This unique molecular relationship is proven by the correction of cleft defects inPax9-deficient mice through Wnt agonist therapies.
Dynactin has two antagonistic regulatory domains and exerts opposing effects on dynein motility
Authors: Kobayashi Takuya , Miyashita Takuya , Murayama Takashi , Toyoshima Yoko Y.
Published: February 2017

Dynactin is a dynein-regulating protein that increases the processivity of dynein movement on microtubules. Recent studies have shown that a tripartite complex of dynein–dynactin–Bicaudal D2 is essential for highly processive movement. To elucidate the regulation of dynein motility by dynactin, we focused on two isoforms (A and B) of dynactin 1 (DCTN1), the largest subunit of dynactin that contains both microtubule- and dynein-binding domains. The only difference between the primary structures of the two isoforms is that DCTN1B lacks the K-rich domain, a cluster of basic residues. We measured dynein motility by single molecule observation of recombinant dynein and dynactin. Whereas the tripartite complex containing DCTN1A exhibited highly processive movement, the complex containing DCTN1B dissociated from microtubules with no apparent processive movement. This inhibitory effect of DCTN1B was caused by reductions of the microtubule-binding affinities of both dynein and dynactin, which is attributed to the coiled-coil 1 domain of DCTN1. In DCTN1A, the K-rich domain antagonized these inhibitory effects. Therefore, dynactin has two antagonistic domains and promotes or suppresses dynein motility to accomplish correct localization and functions of dynein within a cell.
Mitochondrial impairment and rescue in riboflavin responsive neuropathy
Authors: Manole Andreea , Jaunmuktane Zane , Hargreaves Iain , Pandraud Amelie , Salpietro Vincenzo , Pope Simon , Ludtmann Marthe H. R. , Horga Alejandro , Scalco Renata S. , Li Abi , Ashokkumar Balasubramaniem , Lourenço Charles M. , Heales Simon , Horvath Rita , Chinnery Patrick F. , Toro Camilo , Singleton Andrew B. , Jacques Thomas S. , Abramov Andrey Y. , Muntoni Francesco , Hanna Michael G. , Reilly Mary M. , Revesz Tamas , Kullmann Dimitri M. , Jepson James E.C. , Houlden Henry
Published: February 2017

Brown-Vialetto-Van Laere syndrome (BVVLS) represents a phenotypic spectrum of motor, sensory, and cranial nerve neuropathy, often with ataxia, optic atrophy and respiratory problems leading to ventilator-dependence. Loss-of-function mutations in two riboflavin transporter (RFVT) genes,SLC52A2andSLC52A3,have recently been linked to BVVLS. However, the genetic frequency, neuropathology and downstream consequences of RFVT mutations have previously been undefined. By screening a large cohort of 132 patients with early-onset severe sensory, motor and cranial nerve neuropathy we confirmed the strong genetic link between RFVT mutations and BVVLS, identifying twenty-two pathogenic mutations inSLC52A2andSLC52A3,fourteen of which were novel. Brain and spinal cord neuropathological examination of two cases withSLC52A3mutations showed classical symmetrical brainstem lesions resembling pathology seen in mitochondrial disease, including severe neuronal loss in the lower cranial nerve nuclei, anterior horns and corresponding nerves, atrophy of the spinothalamic and spinocerebellar tracts and posterior column-medial lemniscus pathways. Mitochondrial dysfunction has previously been implicated in an array of neurodegenerative disorders. Since riboflavin metabolites are critical components of the mitochondrial electron transport chain (ETC), we hypothesized that reduced riboflavin transport would result in impaired mitochondrial activity, and confirmed this usingin vitroandin vivomodels. ETC complex I and complex II activity were decreased inSLC52A2patient fibroblasts, while global knockdown of the singleDrosophilaRFVT homologue revealed reduced levels of riboflavin, downstream metabolites, and ETC complex I activity. RFVT knockdown inDrosophilaalso resulted in severely impaired locomotor activity and reduced lifespan, mirroring patient pathology, and these phenotypes could be partially rescued using a novel esterified derivative of riboflavin. Our findings indicate mitochondrial dysfunction as a downstream consequence of RFVT gene defects in BVVLS and validate riboflavin esters as a potential therapeutic strategy.
Functional Connectivity Between Somatosensory and Motor Brain Areas Predicts Individual Differences in Motor Learning by Observing
Authors: McGregor Heather R. , Gribble Paul L.
Published: February 2017

Action observation can facilitate the acquisition of novel motor skills, however, there is considerable individual variability in the extent to which observation promotes motor learning. Here we tested the hypothesis that individual differences in brain function or structure can predict subsequent observation-related gains in motor learning. Subjects underwent an anatomical MRI scan and resting-state fMRI scans to assess pre-observation grey matter volume and pre-observation resting-state functional connectivity (FC), respectively. On the following day, subjects observed a video of a tutor adapting her reaches to a novel force field. After observation, subjects performed reaches in a force field as a behavioral assessment of gains in motor learning resulting from observation. We found that individual differences in resting-state FC, but not grey matter volume, predicted post-observation gains in motor learning. Pre-observation resting-state FC between left S1 and bilateral PMd, M1, S1 and left SPL was positively correlated with behavioral measures of post-observation motor learning. Sensory-motor resting-state FC can thus predict the extent to which observation will promote subsequent motor learning.

New & Noteworthy

We show that individual differences in pre-observation brain function can predict subsequent observation-related gains in motor learning. Pre-observation resting-state functional connectivity within a sensory-motor network may be used as a biomarker for the extent to which observation promotes motor learning. This kind of information may be useful if observation is to be used as a way to boost neuroplasticity and sensory motor recovery for patients undergoing rehabilitation for diseases that impair movement such as stroke.
Do maternal antibodies facilitate hemagglutinin imprinting to influenza A viruses encountered early in childhood?
Authors: Gostic Katelyn M. , Ambrose Monique , Worobey Michael , Lloyd-Smith James O.
Published: February 2017

In a recent study, we showed evidence for childhood HA imprinting, a phenomenon in which children develop preferential, lifelong immune memory against zoonotic influenza viruses with hemagglutinin (HA) antigens in the same phylogenetic group as the first influenza virus encountered in childhood (Gostic et al. 2016). Although our original study showed strong, population-level HA imprinting effects, it did not resolve the underlying immunological mechanisms.

Similar immune imprinting phenomena, where individuals preferentially recall immune responses primed early in life, also influence seasonal influenza epidemiology via antigenic seniority (Lessler et al. 2012) and original antigenic sin (Francis 1960), yet the mechanisms underlying all these childhood immune imprinting phenomena remain poorly understood (Cobey & Hensley 2017). A recent letter from Dr. H. Lemke (Lemke 2017) suggested that these childhood imprinting effects might be mediated by the combined action of maternal antibodies (mAbs) and influenza antigen. In other words, that imprinting may require that children are exposed to influenza A virus in the first year of life, while maternal antibodies are still present.
Genetic Architecture and Molecular Networks Underlying Leaf Thickness in Desert-Adapted TomatoSolanum pennellii
Authors: Coneva Viktoriya , Frank Margaret H. , de Luis Balaguer Maria A. , Li Mao , Sozzani Rosangela , Chitwood Daniel H.
Published: February 2017

Thicker leaves allow plants to grow in water-limited conditions. However, our understanding of the genetic underpinnings of this highly functional leaf shape trait is poor. We used a custom-built confocal profilometer to directly measure leaf thickness in a set of introgression lines (ILs) derived from the desert tomato speciesSolanum pennellii, and identified quantitative trait loci (QTL). We report evidence of a complex genetic architecture of this trait and roles for both genetic and environmental factors. Several ILs with thick leaves have dramatically elongated palisade mesophyll cells and, in some cases, increased leaf ploidy. We characterized thick ILs 2-5 and 4-3 in detail and found increased mesophyll cell size and leaf ploidy levels, suggesting that endoreduplication underpins leaf thickness in tomato. Next, we queried the transcriptomes and inferred Dynamic Bayesian Networks of gene expression across early leaf ontogeny in these lines to compare the molecular networks that pattern leaf thickness. We show that thick ILs shareS. pennellii-like expression profiles for putative regulators of cell shape and meristem determinacy, as well as a general signature of cell cycle related gene expression. However, our network data suggest that leaf thickness in these two lines is patterned by at least partially distinct mechanisms. Consistent with this hypothesis, double homozygote lines combining introgression segments from these two ILs show additive phenotypes including thick leaves, higher ploidy levels and larger palisade mesophyll cells. Collectively, these data establish a framework of genetic, anatomical, and molecular mechanisms that pattern leaf thickness in desert-adapted tomato.
Tuning transcriptional regulation through signaling: A predictive theory of allosteric induction
Authors: Razo-Mejia Manuel , Barnes Stephanie L. , Belliveau Nathan M. , Chure Griffin , Einav Tal , Lewis Mitchell , Phillips Rob
Published: February 2017

Allosteric regulation is found across all domains of life, yet we still lack simple, predictive theories that directly link the experimentally tunable parameters of a system to its input-output response. To that end, we present a general theory of allosteric transcriptional regulation using the Monod-Wyman-Changeux model. We rigorously test this model using the ubiquitous simple repression motif in bacteria by first predicting the behavior of strains that span a large range of repressor copy numbers and DNA binding strengths and then constructing and measuring their response. Our model not only accurately captures the induction profiles of these strains but also enables us to derive analytic expressions for key properties such as the dynamic range and [EC50]. Finally, we derive an expression for the free energy of allosteric repressors which enables us to collapse our experimental data onto a single master curve that captures the diverse phenomenology of the induction profiles.
The role of accounting for managing innovation processes when relationships matter
Authors: Lind Johnny
Published: February 2017

Purpose

This paper studies how accounting information is used by actors in an innovation process. It investigates how accounting information influences and is influenced by the different actors. The purpose of this paper is to develop a more thorough understanding of the role of accounting in making the choices that form temporary solutions.

Design/methodology/approach

An in-depth case study of the development of a standard software release within the telecom industry.

Findings

This study has shown that accounting was a key ingredient when temporary solutions were formed in the innovation processes. Actors used accounting to stabilize the content of the release in the formation of the gate documents and used accounting to destabilize the content between the temporary solutions. It is difficult to evaluate whether the use of accounting improved or harmed the innovation. Further, the study also revealed that the use of accounting influenced and was influenced by previous and prospective future deals. This put new challenges on the use of accounting because it involved negotiation processes that influenced the accounting figures.

Practical implications

The findings provide insights into the procedures for finding temporary solutions in the innovation process and the role of accounting in these procedures.

Originality/value

This paper contributes by providing a more thorough understanding of the role of accounting regarding the choices that comprise the temporary solutions within the innovation process. In addition, it shows how accounting has a critical role both for settling on and modifying temporary solutions. Hence, the research demonstrated how studies of the role of accounting in innovation processes can contribute to the industrial network approach by giving a more thorough understanding of network dynamics and the process of attaining stability and instability in business networks.
Health monitoring impact on non-repairable component supply methods
Authors: Vandawaker Robert M. , Jacques David R. , Ryan Erin T. , Huscroft Joseph R. , Freels Jason K.
Published: February 2017

Purpose

From on-board automotive diagnostics to real-time aircraft state of health, the implementation of health monitoring and management systems are an increasing trend. Further, reductions in operating budgets are forcing many companies and militaries to consider new operating and support environments. Combined with longer service lives for aircraft and other systems, maintenance and operations processes must be reconsidered. The majority of research efforts focus on health monitoring techniques and technologies, leaving others to determine the maintenance and logistics impact on the systems. The paper aims to discuss these issues.

Design/methodology/approach

This research analyzes the impact of a health monitoring system on a squadron of aircraft. Flight, maintenance and logistics operations are stochastically modeled to determine the impact of program decisions on supply metrics. An arena discrete event simulation is utilized to conduct this research on 20 components on each of the 12 aircraft modeled. Costs and availability are recorded for comparison across three sparing scenarios to include economic order quantity (EOQ) for baseline and health monitoring cases and a just-in-time (JIT) health monitoring set of simulations.

Findings

Data are presented for EOQ and JIT supply methods. A comparison of health monitoring enabled supply to current methods shows cost savings and availability gains. The different methodologies are compared and discussed as a trade-space for programmatic decisions.

Originality/value

This work demonstrates the ability of health monitoring systems and condition based maintenance to affect supply ordering decisions. The development of trade-spaces within operating environments is demonstrated along with the ability to conduct cost benefit analyses.
Operational integration in a craft-oriented small enterprise
Authors: Gamme Inger , Seim Eva Amdahl , Lodgaard Eirin , Andersen Bjørn
Published: February 2017

Purpose

Many leisure boat manufacturers have thrived on designing and building highly customized boats based on longstanding traditions of craftsmanship. To achieve efficient value chains, it is not enough to optimize each process step, but also important to achieve a smooth flow through the dependencies between each process steps. The purpose of this paper is to focus on assessing enablers and disablers for operational integration in a craft-oriented small enterprise.

Design/methodology/approach

One case company has been studied, to identify enablers and disablers for operational integration in the value chain. The research methodology is based on semi-structured interviews with selected persons from different levels within the company.

Findings

The results indicate the importance of management promotion and support of integration and a strong relationship between foremen and operators. Furthermore, to avoid functional myopias, mechanisms to encourage horizontal integration could be useful. Small company and informal culture make integration easier. However, to further establish a common standardized platform, could be necessary. Even small physical barriers in the layout were experienced to affect the integration negatively.

Research limitations/implications

This has been an exploratory study of one single craft-oriented enterprise; hence it is difficult to generalize.

Practical implications

Based on empirical findings from the case study, recommendations on how to achieve better operational integration will be presented.

Originality/value

The research initiative provides knowledge experience of operational integration from a case study in one company within craft and artisan sector in Norway.
An Unexpected Finding in SUDEP Involving a Child: Focal Myocardial Infarct Adjacent to Bundle of His
Authors: Neff Jadee L. , Lin Peter T.
Published: February 2017

Sudden unexpected death in epilepsy (SUDEP) is a nontraumatic, nondrowning death of an individual with epilepsy in which an autopsy with appropriate ancillary studies does not identify a cause of death. The mechanism of death in SUDEP is unknown, but is thought to involve cardiac and/or respiratory mechanisms. Research in SUDEP is hindered by a lack of consensus regarding required components of a death investigation before a cause of death may be certified as SUDEP. Histopathologic examination of the cardiac conduction system is not routinely performed in SUDEP death investigations. We present a case of SUDEP where histopathologic examination of the cardiac conduction system revealed a focal myocardial infarct of the summit of the ventricular septum abutting the bundle of His, which potentially provides insight into the mechanism of SUDEP for this particular case, and suggests that routine examination of the cardiac conduction system in SUDEP may be beneficial.
Suppression of anti‐drug antibodies to infliximab or adalimumab with the addition of an immunomodulator in patients with inflammatory bowel disease
Authors: Strik A. S. , van den Brink G. R. , Ponsioen C. , Mathot R. , Löwenberg M. , D'Haens G. R.
Published: February 2017

Background

Loss of response to anti‐tumour necrosis factor (TNF) therapy in patients with inflammatory bowel disease (IBD) is often caused by anti‐drug antibody formation with neutralisation of drug effect. Addition of an immunomodulator has been suggested to reduce immunogenicity, leading to regained response.

Aim

To investigate whether addition of an immunomodulator to anti‐TNF monotherapy could lead to anti‐drug antibody suppression and regained clinical response in IBD patients.

Methods

We retrospectively collected measurements of infliximab or adalimumab serum concentrations and anti‐drug antibodies to identify anti‐drug positive patients with loss response who were given an immunomodulator.

Results

Anti‐drug antibodies against infliximab and adalimumab were detected in 98/376 (26%) and in 61/226 (27%) patients, respectively. Immunomodulators were given to 17/159 patients. Clinical response was recaptured in 6/10 patients receiving a thiopurine and in all (7/7) patients receiving methotrexate. In 7/8 patients on infliximab, serum concentrations increased (median 2.84 μg/mL; IQR: 1.19–4.98) and in 6/9 patients on adalimumab (median 3.10 μg/mL; IQR: 1.45–4.45). This was accompanied by a decrease in anti‐drug antibodies to undetectable levels (median 11 months for both anti‐TNF agents). In 23 patients, no immunomodulator was added but anti‐TNF interval was shortened (17/23) or dosage was increased (6/23), which resulted in a clinical response in 10/17 and 2/6 patients, respectively.

Conclusion

In 77% of IBD patients with loss of response due to immunogenicity, addition of immunomodulator resulted in undetectable anti‐drug antibody levels, increased serum drug concentrations and regained clinical response. This strategy should be considered in this patient population before switching to other agents.
Desire to be ethical or ability to self‐control: Which is more crucial for ethical behavior?
Authors: Rua Tuvana , Lawter Leanna , Andreassi Jeanine
Published: February 2017

Promoting ethical decisions and behaviors is challenging for any organization. Yet managers are still required to make ethical decisions under conditions which deplete their self‐control resources, such as high stress and long hours. This study examines the relationships among symbolic and internal moral identity, self‐control, and ethical behavior, and investigates whether self‐control acts as the mechanism through which moral identity leads to ethical behavior. Findings indicate that internal moral identity overrides symbolic moral identity in the relationship with self‐control and that self‐control fully mediates the relationship between internal moral identity and ethical behavior. The implications for organizations is that while rules, procedures, and ethics training are useful, managers with a strong moral compass will be more likely to practice self‐control leading to more ethical behaviors.
From piloting e‐submission to electronic management of assessment (EMA): Mapping grading journeys
Authors: Vergés Bausili Anna
Published: February 2017

The increasing interest in electronic management of assessment is a sign of a gradual institutionalisation of e‐submission and e‐marking technologies in UK Higher Education. The effective adoption of these technologies requires a managed approach, especially a detailed understanding of current assessment practices within the institution and the development of new or adapted business processes. The findings from close participant observation of assessment processes over a 2‐year period across a large Faculty reveal that three independent variables around (1) initial marking, (2) internal quality assurance and (3) the timing of the return of e‐feedback to students, determine variance in grading journeys. Despite the apparent wide variety of processes, five major grading journeys prevail: three varieties of moderation (moderation of multiple markers and moderation of single markers either before or after grades and feedback are released to students); and two forms of second marking (either blind or open to peers). Within an institution, the identification of major workflows is fundamental to both an effective implementation of assessment technologies and in conducting change. The identification of major workflows across UK Higher Education Institutions remains critical to attain the necessary software development from global vendors.
Transcriptomic analyses of RNA‐binding proteins reveal eIF3c promotes cell proliferation in hepatocellular carcinoma
Authors: Li Tangjian , Li Shengli , Chen Di , Chen Bing , Yu Tao , Zhao Fangyu , Wang Qifeng , Yao Ming , Huang Shenglin , Chen Zhiao , He Xianghuo
Published: February 2017

RNA‐binding proteins (RBPs) play fundamental roles in the RNA life cycle. The aberrant expression of RBPs is often observed in human disease, including cancer. In this study, we screened for the expression levels of 1542 human RBPs in The Cancer Genome Atlas liver hepatocellular carcinoma samples and found 92 consistently upregulated RBP genes in HCC compared with normal samples. Additionally, we undertook a Kaplan–Meier analysis and found that high expression of 15 RBP genes was associated with poor prognosis in patients with HCC. Furthermore, we found that eIF3c promotes HCC cell proliferation in vitro as well as tumorigenicity in vivo. Gene Set Enrichment Analysis showed that high eIF3c expression is positively associated with KRAS, vascular endothelial growth factor, and Hedgehog signaling pathways, all of which are closely associated with specific cancer‐related gene sets. Our study provides the basis for further investigation of the molecular mechanism by which eIF3c promotes the development and progression of HCC.
MicroRNA‐135a‐3p as a promising biomarker and nucleic acid therapeutic agent for ovarian cancer
Authors: Fukagawa Satoshi , Miyata Kohei , Yotsumoto Fusanori , Kiyoshima Chihiro , Nam Sung Ouk , Anan Haruchika , Katsuda Takahiro , Miyahara Daisuke , Murata Masaharu , Yagi Hiroshi , Shirota Kyoko , Yasunaga Shin'ichiro , Kato Kiyoko , Miyamoto Shingo
Published: February 2017

Ovarian cancer is the most lethal gynecologic malignancy. Recently, several molecularly targeted anticancer agents have been developed for ovarian cancer; however, its prognosis remains extremely poor. The development of molecularly targeted therapy, as well as companion diagnostics, is required to improve outcomes for patients with ovarian cancer. In this study, to identify microRNAs (miRNAs) involved in the progression of ovarian cancer we analyzed serum miRNAs in patients with ovarian cancer using miRNA array and quantitative RT‐PCR and examined the anticancer properties of miRNA expression in ovarian cancer cells. In patients with ovarian cancer, high amount of miR‐135a‐3p in serum samples was significantly associated with favorable clinical prognosis. The amount of miR‐135a‐3p was significantly decreased in patients with ovarian cancer compared with patients with ovarian cysts or normal ovaries. In SKOV‐3 and ES‐2 human ovarian cancer cells, enhanced expression of miR‐135a‐3p induced drug sensitivity to cisplatin and paclitaxel and suppressed cell proliferation and xenograft tumor growth. These findings suggest that miR‐135a‐3p may be considered as a biomarker and a therapeutic agent in ovarian cancer.
Drinkers' identification with varying alcohol consumption prototypes
Authors: Pettigrew Simone , Jongenelis Michelle I. , Pratt Iain S. , Slevin Terry , Chikritzhs Tanya
Published: February 2017

Introduction and Aims

Efforts to reduce excessive alcohol consumption need to take into account drinkers' perceptions of their risk of alcohol‐related harm. The aim of the present study was to profile adult Australian drinkers according to their self‐identification with various drinker prototypes to determine the extent to which these prototypes are associated with perceived and actual risk of alcohol‐related harm.

Design and Methods

A large web panel provider disseminated an online survey to a national sample of 2168 drinkers aged 18+ years who consumed alcohol at least twice per month. Respondents reported whether they considered themselves to be a light, occasional, social, heavy or binge drinker. The nominated category was compared with perceived and actual risk of alcohol‐related harm.

Results

The prototype most commonly nominated by respondents was ‘social drinker’ (45%), and the least common was ‘binge drinker’ (7%). Although the heaviest drinkers in terms of actual reported consumption typically selected prototypes indicative of harmful consumption, many of those selecting prototypes indicative of moderate consumption were at risk of alcohol‐related harm.

Discussion and Conclusions

Many adult drinkers may be unaware of their risk of alcohol‐related harm. The results suggest that there may be a need to recalibrate Australian drinkers' perceptions of high‐risk drinking. [Pettigrew S, Jongenelis MI, Pratt IS, Slevin T, Chikritzhs T. Drinkers' identification with varying alcohol consumption prototypes. Drug Alcohol Rev 2017;36:464‐467]
Children's selective trust decisions: rational competence and limiting performance factors
Authors: Hermes Jonas , Behne Tanya , Bich Anna Elisa , Thielert Christa , Rakoczy Hannes
Published: February 2017

Recent research has amply documented that even preschoolers learn selectively from others, preferring, for example, reliable over unreliable and competent over incompetent models. It remains unclear, however, what the cognitive foundations of such selective learning are, in particular, whether it builds on rational inferences or on less sophisticated processes. The current study, therefore, was designed to test directly the possibility that children are in principle capable of selective learning based on rational inference, yet revert to simpler strategies such as global impression formation under certain circumstances. Preschoolers (N = 75) were shown pairs of models that either differed in their degree of competence within one domain (strong vs. weak or knowledgeable vs. ignorant) or were both highly competent, but in different domains (e.g., strong vs. knowledgeable model). In the test trials, children chose between the models for strength‐ or knowledge‐related tasks. The results suggest that, in fact, children are capable of rational inference‐based selective trust: when both models were highly competent, children preferred the model with the competence most predictive and relevant for a given task. However, when choosing between two models that differed in competence on one dimension, children reverted to halo‐style wide generalizations and preferred the competent models for both relevant and irrelevant tasks. These findings suggest that the rational strategies for selective learning, that children master in principle, can get masked by various performance factors.
Functional connectivity in amygdalar‐sensory/(pre)motor networks at rest: new evidence from the Human Connectome Project
Authors: Toschi Nicola , Duggento Andrea , Passamonti Luca
Published: February 2017

The word ‘e‐motion’ derives from the Latin word ‘ex‐moveo’ which literally means ‘moving away from something/somebody’. Emotions are thus fundamental to prime action and goal‐directed behavior with obvious implications for individual's survival. However, the brain mechanisms underlying the interactions between emotional and motor cortical systems remain poorly understood. A recent diffusion tensor imaging study in humans has reported the existence of direct anatomical connections between the amygdala and sensory/(pre)motor cortices, corroborating an initial observation in animal research. Nevertheless, the functional significance of these amygdala‐sensory/(pre)motor pathways remain uncertain. More specifically, it is currently unclear whether a distinct amygdala‐sensory/(pre)motor circuit can be identified with resting‐state functional magnetic resonance imaging (rs‐fMRI). This is a key issue, as rs‐fMRI offers an opportunity to simultaneously examine distinct neural circuits that underpin different cognitive, emotional and motor functions, while minimizing task‐related performance confounds. We therefore tested the hypothesis that the amygdala and sensory/(pre)motor cortices could be identified as part of the same resting‐state functional connectivity network. To this end, we examined independent component analysis results in a very large rs‐fMRI data‐set drawn from the Human Connectome Project (n = 820 participants, mean age: 28.5 years). To our knowledge, we report for the first time the existence of a distinct amygdala‐sensory/(pre)motor functional network at rest. rs‐fMRI studies are now warranted to examine potential abnormalities in this circuit in psychiatric and neurological diseases that may be associated with alterations in the amygdala‐sensory/(pre)motor pathways (e.g. conversion disorders, impulse control disorders, amyotrophic lateral sclerosis and multiple sclerosis).
Randomized, double‐blind, placebo‐controlled phase 2 study of ganaxolone as add‐on therapy in adults with uncontrolled partial‐onset seizures
Authors: Sperling Michael R. , Klein Pavel , Tsai Julia
Published: February 2017

Objective

To evaluate the efficacy and safety of ganaxolone as adjunctive therapy in adults with uncontrolled partial‐onset seizures despite taking up to three concomitant antiepileptic drugs (AEDs).

Methods

Adults aged 18–69 years and refractory to conventional AEDs were enrolled in a multicenter, double‐blind, placebo‐controlled trial. After an 8‐week baseline period, patients were randomized 2:1 to ganaxolone 1,500 mg/day or placebo for a 10‐week treatment period (2‐week forced titration and 8‐week maintenance) followed by either tapering or entry into an open‐label extension study. The primary endpoint was mean weekly seizure frequency. Secondary endpoints included the proportion of patients experiencing ≥50% reduction in seizure frequency (responder rate), percent change in mean weekly seizure frequency, seizure‐free days, and quality of life. Safety and tolerability assessments included adverse events (AEs), treatment discontinuation, and clinical laboratory evaluations. Efficacy analyses were performed on the intent‐to‐treat population.

Results

Of 147 randomized patients (98 ganaxolone, 49 placebo), 131 completed the study; 95% of participants titrated up to 1,500 mg/day and 78% maintained this dose. From baseline to endpoint, mean weekly seizure frequency decreased with ganaxolone (6.5–5.2) versus placebo (9.2–10.8), representing an 11.4% decrease versus placebo (p = 0.0489, analysis of covariance [ANCOVA]). Mean percent change from baseline was −17.6% with ganaxolone versus 2.0% with placebo (p = 0.0144, Kruskal‐Wallis test). Responder rates were 24% with ganaxolone versus 15% with placebo (p = 0.19). Discontinuation due to adverse events was similar with ganaxolone (7.1%) and placebo (6.1%). Common adverse events were mild to moderate in severity and included dizziness (16.3% vs. 8.2%), fatigue (16.3% vs. 8.2%), and somnolence (13.3% vs. 2.0%).

Significance

Ganaxolone 1,500 mg/day reduced partial‐onset seizure frequency and was generally safe and well tolerated in this phase 2 study. These results support continued development of ganaxolone for adult patients with refractory partial‐onset seizures.
Modelling of overload effects on fatigue crack initiation in case of carbon steel
Authors: Mlikota M. , Schmauder S. , Božić Ž. , Hummel M.
Published: February 2017

This paper deals with the modelling of short crack initiation within a microstructure of medium carbon steel under fatigue loading, as well as with the influence of overload on the crack initiation period. Studies on the long crack growth show that the overload introduces first an increase in the crack growth rate that is then followed with a decrease, a so‐called retardation. A micro‐model containing the microstructure of the material is analysed using the finite element method in combination with a model for crack development – the assessment of number of cycles needed for crack initiation was based on the Tanaka–Mura equation. The analysis brings in a correlation between the crack growth rate and the crack length together with the effects of the overload on the crack growth rate. The overload is found to accelerate the short crack growth; however, the following retardation could not be captured due to the inability of the model to produce residual stresses, which are considered to be the main cause of the retardation effect.
Honokiol protects skin cells against inflammation, collagenolysis, apoptosis, and senescence caused by cigarette smoke damage
Authors: Costa Adilson , Facchini Gustavo , Pinheiro Ana Lúcia T. A. , da Silva Michelle S. , Bonner Michael Y. , Arbiser Jack , Eberlin Samara
Published: February 2017

Background

Pollution, especially cigarette smoke, is a major cause of skin damage.

Objectives

To assess the effects of the small molecule polyphenol, honokiol, on reversing cigarette smoke‐induced damage in vitro to relevant skin cells.

Methods

Keratinocytes (HaCat) cultures were exposed to cigarette smoke and, after 48 hours, IL‐1α and IL‐8 were measured in cell supernatants. Moreover, TIMP‐2 production, apoptosis rate, and senescence β‐galactosidase expression were evaluated in primary human foreskin fibroblasts (HFF‐1) cultures.

Results

Honokiol at 10 μm reduced IL‐1α production by 3.4 folds (P < 0.05) and at 10 and 20 μm reduced IL‐8 by 23.9% and 53.1% (P < 0.001), respectively, in HaCat keratinocytes. In HFF‐1, honokiol restored TIMP‐2 production by 96.9% and 91.9% (P < 0.001), respectively, at 10 and 20 μm, as well as reduced apoptosis by 47.1% (P < 0.001) and 41.3% (P < 0.01), respectively. Finally, honokiol reduced senescence‐associated β‐galactosidase expression in HFF‐1.

Conclusion

Honokiol protects both HFF‐1 and HaCat against cigarette smoke‐induced inflammation, collagenolysis, apoptosis, and senescence.
Expression levels of transcription factor PU.1 and interleukin‐9 in atopic dermatitis and their relation to disease severity and eruption types
Authors: Hamza Ashraf M. , Omar Salma S. , Abo El‐Wafa Reham A. H. , Elatrash Marwa J.
Published: February 2017

Background

The role of immunological factors in atopic dermatitis (AD) pathogenesis is well established. T‐helper (TH) cells are central in AD pathogenesis. A relatively new subset of T cells, Th9 cells, was shown to be involved in the development of allergic asthma and allergic rhinitis, while its role in AD is still to be investigated. This study aimed to measure gene expression levels of interleukin‐9 (IL‐9) and PU.1, and to examine relationships with disease severity, serum IgE, and eruption types in AD patients.

Methods

The study enrolled 30 AD patients, 30 psoriasis patients, and 30 healthy subjects. The severity of AD was assessed using the SCORAD index. IL‐9 and PU.1 expressions were measured by using real‐time quantitative polymerase chain reaction (RQ‐PCR). Serum IgE was measured by IgE (human) enzyme‐linked immunosorbent assay (ELISA) Kit.

Results

IL‐9 and PU.1 gene expressions were significantly higher in AD patients than in controls (P1 = 0.007, P2 < 0.001, respectively). In the atopic dermatitis patients, expression of IL‐9 and PU.1 were significantly positively correlated with SCORAD index (P1 = 0.004, P2 = 0.002) and clinically with erythema and edema scores. IL‐9 and PU.1 expressions were positively significantly correlated (P = 0.005) and positively correlated with serum IgE in the AD group (P1 = 0.017, P2 = 0.023). No significant difference was noted between AD patients with or without histories of other atopies regarding expression levels of IL‐9 and PU.1 (P1 = 0.677, P2 = 0.135).

Conclusions

PU.1 and IL‐9 may play a role in AD pathogenesis and relate to disease severity and clinical eruption types.