bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of entrepreneurial passion on entrepreneurial orientation with the mediating role of entrepreneurial alertness for technology-based firms in Mexico
Authors: Montiel Campos Héctor
Published: April 2017

Purpose

The purpose of this paper is to analyze the mediating role of entrepreneurial alertness in the relationship between entrepreneurial passion and entrepreneurial orientation (EO).

Design/methodology/approach

This is a quantitative study using a self-report survey for information gathering. The hypotheses are tested with a sample of 112 entrepreneurs from technology-based firms in Mexico using hierarchical regression analysis. The study follows procedural and statistical recommendations from previous studies in order to strengthen the results.

Findings

The results demonstrate a significant and positive relationship between entrepreneurial passion and EO, and this relationship is mediated for each dimension of entrepreneurial alertness.

Research limitations/implications

Although there are interesting results in the study, some limitations should be recognized. First, it is important to consider the stage in which the firm is operating because it influences the firm’s behavior. Second, the generalization of the results should be validated in non-technology-based firms that operate in different contexts and conditions. The study’s findings have implications for small business support programs and entrepreneurs.

Originality/value

The study contributes to the emerging research of entrepreneurial passion in the field of entrepreneurship and to the scarce empirical research on entrepreneurial alertness. Both constructs are related to one of the most representative topics in the field, as is EO.
The design process of corporate universities: a stakeholder approach
Authors: Patrucco Andrea Stefano , Pellizzoni Elena , Buganza Tommaso
Published: April 2017

Purpose

Corporate universities (CUs) have been experiencing tremendous growth during the past years and can represent a real driving force for structured organizations. The paper aims to define the process of CU design shaped around company strategy. For each step, the authors propose specific roles, activities and methods.

Design/methodology/approach

The paper exploits some managerial theories and past research on CUs to draw a two-step framework for their design and development process, then tests (and validating) it through action research and applies its guidelines to two different case studies.

Findings

The authors conclude the CU design process can be divided into two steps (development and management), with specific roles assigned to the different activities, and this allocation represents a prerequisite for the CU project success. Moreover, flexibility and potential recycles should be considered when configuring the process.

Originality/value

The paper is original in two ways: it proposes a framework for CU design and development (which is unique in its type) and an application of this framework to two real cases, discussing its benefits, criticalities and limitations (thus ensuring generalizability).
Solder joint defect classification based on ensemble learning
Authors: Wu Hao
Published: April 2017

Purpose

This paper aims to inspect the defects of solder joints of printed circuit board in real-time production line, simple computing and high accuracy are primary consideration factors for feature extraction and classification algorithm.

Design/methodology/approach

In this study, the author presents an ensemble method for the classification of solder joint defects. The new method is based on extracting the color and geometry features after solder image acquisition and using decision trees to guarantee the algorithm’s running executive efficiency. To improve algorithm accuracy, the author proposes an ensemble method of random forest which combined several trees for the classification of solder joints.

Findings

The proposed method has been tested using 280 samples of solder joints, including good and various defect types, for experiments. The results show that the proposed method has a high accuracy.

Originality/value

The author extracted the color and geometry features and used decision trees to guarantee the algorithm's running executive efficiency. To improve the algorithm accuracy, the author proposes using an ensemble method of random forest which combined several trees for the classification of solder joints. The results show that the proposed method has a high accuracy.
Study of direct soldering of silicon and copper substrate by use of Bi-based solders with lanthanides addition
Authors: Kolenak Roman
Published: April 2017

Purpose

This paper aims to investigate the effect of solder alloying with a small amount of La and Y on bond formation with the Si and Cu substrates.

Design/methodology/approach

Bi2La and Bi2Y solders were studied. Soldering was performed using a fluxless method in air and with ultrasonic activation.

Findings

It was found that in the process of ultrasonic soldering, the La and Y were distributed at the interface with Si and Cu substrates, which enhanced the bond formation. Addition of La or Y elements in a Bi-based solder also ensured wetting of non-metallic materials such as Si, Al2O3 and SiC ceramics.

Originality/value

The addition of lanthanides offers a method for ensuring wetting of non-metallic materials. The bond with Si was of an adhesive character without the formation of a new contact interlayer. This resulted in lower shear strength of the bond with Si (8-10 MPa). The shear strength of the bond with a Cu substrate was 22-30 MPa.
The role of transcriptomes linked with responses to light environment on seedling mortality in a subtropical forest, China
Authors: Han Baocai , Umaña María Natalia , Mi Xiangcheng , Liu Xiaojuan , Chen Lei , Wang Yunquan , Liang Yu , Wei Wei , Ma Keping
Published: April 2017

Differences in seedling survival in trees have a lasting imprint on seedling, juvenile and adult community structure. Identifying the drivers of these differences, therefore, is a critical research objective that ultimately requires knowledge regarding how organismal function interacts with the local environment to influence survival rates.

In tree communities, differences in light use strategies are frequently invoked to explain differences in seedling demographic performance through growth and survival trade‐offs. For example, shade‐tolerant species grow slowly and have higher survival rates, whereas shade‐intolerant species grow quickly but have lower survival rates. Thus, functional traits related to photosynthesis should be strong predictors of demographic rates, but results in the literature are mixed indicating that additional or alternative information regarding organismal function should be considered.

Here, we provide a community‐wide inventory of transcriptomes in a subtropical tree community. This information is utilized to determine the degree to which species share homologous genes related to gene ontologies for light use and harvesting. These species similarities are used in neighbourhood generalized linear mixed‐effects models of seedling survival that evaluated seedling survival as a function of the transcriptomic, functional trait and phylogenetic composition of the local neighbourhood. The results show neighbourhood similarity in three of the 15 gene ontologies evaluated are significantly related to survival rates based on neighbourhood composition. For two of these ontologies, survival rates increase when neighbours are similar in their gene tree composition indicating the importance of abiotic filtering and performance hierarchies.

Synthesis. The present work takes a novel approach by sequencing the transcriptomes of naturally co‐occurring tree species in a subtropical forest in China. The results show that the transcriptomic similarity of species is a significant predictor of differential survival. The study demonstrates that exploring the functional genomic similarity of non‐model species in nature has the potential to increase the breadth and depth of our understanding of how gene function influences species co‐occurrence and population dynamics in communities.
Evaluation of iron‐fortified Feta cheese for physicochemical and sensory properties
Authors: Jalili Maryam , Ehsani Mohammad Reza , Mazloumi Mohammad Taghi
Published: April 2017

Standardised cow's milk (fat 3 g/100 g) was used to manufacture Feta cheese fortified with 40, 60 and 80 mg of iron/kg cheese using ferrous sulphate (FeSO4), ferric chloride (FeCl3), ferric pyrophosphate (Fe4 (P2O7)3) and microencapsulated ferrous sulphate. Chemical composition and sensory characteristics of fortified cheeses were determined after 60 days of ripening, during which the iron content and thiobarbituric acid (TBA) values were measured. The metallic taste, colour, flavour, overall score and TBA values were statistically (P < 0.05) affected by the source and concentration of iron. The best quality was found in cheeses fortified with 40 mg/kg of microencapsulated ferrous sulphate.
Brazilian Agriculture: Is it all about the Large Farms?
Authors: Helfand Steven M. , Rada Nicholas E. , Magalhães Marcelo M.
Published: April 2017

Too often Brazil's agricultural sector is associated primarily with farms operating thousands of hectares in the vast savannah known as the cerrado. Our purpose is to demonstrate that this association is inaccurate, that there exists enormous heterogeneity within the sector across farm sizes. To this end, we separately examine how 1985–2006 total factor productivity (TFP) growth and 2006 production scale vary over farm sizes. We draw on microdata from Brazil's agricultural censuses, aggregated into five farm size classes at the municipality level. While TFP growth has been high on the largest farms, it has been slightly higher on the smallest farms. And when attention is restricted to the 9.5 per cent of farms that accounted for 86 per cent of total production value – those that we designate as ‘large scale’ – it is clear that most were small and medium‐sized farms located in the South and Southeast. Taken together, these results indicate that Brazil's agricultural success has not been only about the large farms. As scholars and policymakers debate the costs and benefits of replicating Brazil's ‘Agricultural Miracle’ in other parts of the world, it is critical not to overlook the contributions of small and medium‐sized farms.
Squamate Conserved Loci (SqCL): A unified set of conserved loci for phylogenomics and population genetics of squamate reptiles
Authors: Singhal Sonal , Grundler Maggie , Colli Guarino , Rabosky Daniel L.
Published: April 2017

The identification of conserved loci across genomes, along with advances in target capture methods and high‐throughput sequencing, has helped spur a phylogenomics revolution by enabling researchers to gather large numbers of homologous loci across clades of interest with minimal upfront investment in locus design. Target capture for vertebrate animals is currently dominated by two approaches—anchored hybrid enrichment (AHE) and ultraconserved elements (UCE)—and both approaches have proven useful for addressing questions in phylogenomics, phylogeography and population genomics. However, these two sets of loci have minimal overlap with each other; moreover, they do not include many traditional loci that that have been used for phylogenetics. Here, we combine across UCE, AHE and traditional phylogenetic gene locus sets to generate the Squamate Conserved Loci set, a single integrated probe set that can generate high‐quality and highly complete data across all three loci types. We use these probes to generate data for 44 phylogenetically disparate taxa that collectively span approximately 33% of terrestrial vertebrate diversity. Our results generated an average of 4.29 Mb across 4709 loci per individual, of which an average of 2.99 Mb was sequenced to high enough coverage (≥10×) to use for population genetic analyses. We validate the utility of these loci for both phylogenomic and population genomic questions, provide a comparison among these locus sets of their relative usefulness and suggest areas for future improvement.
Effective mosquito and arbovirus surveillance using metabarcoding
Authors: Batovska J. , Lynch S. E. , Cogan N. O. I. , Brown K. , Darbro J. M. , Kho E. A. , Blacket M. J.
Published: April 2017

Effective vector and arbovirus surveillance requires timely and accurate screening techniques that can be easily upscaled. Next‐generation sequencing (NGS) is a high‐throughput technology that has the potential to modernize vector surveillance. When combined with DNA barcoding, it is termed ‘metabarcoding.’ The aim of our study was to establish a metabarcoding protocol to characterize pools of mosquitoes and screen them for virus. Pools contained 100 morphologically identified individuals, including one Ross River virus (RRV) infected mosquito, with three species present at different proportions: 1, 5, 94%. Nucleic acid extracted from both crude homogenate and supernatant was used to amplify a 269‐bp section of the mitochondrial cytochrome c oxidase subunit I (COI) locus. Additionally, a 67‐bp region of the RRV E2 gene was amplified from synthesized cDNA to screen for RRV. Amplicon sequencing was performed using an Illumina MiSeq, and bioinformatic analysis was performed using a DNA barcode database of Victorian mosquitoes. Metabarcoding successfully detected all mosquito species and RRV in every positive sample tested. The limits of species detection were also examined by screening a pool of 1000 individuals, successfully identifying the species and RRV from a single mosquito. The primers used for amplification, number of PCR cycles and total number of individuals present all have effects on the quantification of species in mixed bulk samples. Based on the results, a number of recommendations for future metabarcoding studies are presented. Overall, metabarcoding shows great promise for providing a new alternative approach to screening large insect surveillance trap catches.
Improving models of urban greenspace: from vegetation surface cover to volumetric survey, using waveform laser scanning
Authors: Casalegno Stefano , Anderson Karen , Hancock Steven , Gaston Kevin J.
Published: April 2017

Urban greenspace has a major impact on human health and quality of life, and thus the way in which such green infrastructure is constructed, managed and maintained is of critical importance. A range of studies have demonstrated the relationship between the areal coverage and distribution of vegetation and the provision of multiple urban ecosystem services. It is not known how sensitive findings are to the spatial resolution of the underlying data relative to the grain size of urban land cover heterogeneity. Moreover, little is known about the three‐dimensional (3D) structure of urban vegetation and delivery of services, and addressing such questions is limited by the availability of data describing canopy structure from the tree tops to the ground.

Waveform airborne laser scanning (lidar) offers a new way of capturing 3D data describing vegetation structure. We generated voxels (volumetric pixels) from waveform lidar (1·5 m resolution), differentiated vegetation layers using height as a determinant, and computed statistics on surface cover, volume and volume density per stratum. We then used a range of widely available remote sensing products with varying spatial resolution (1 to 100 m) to map the same greenspace, and compared results to those from the waveform lidar survey.

We focused on data from three urban zones in the UK with distinct patterns of vegetation cover. We found −3%, +7·5% and +26·1% differences in green surface cover compared with, respectively, town planning maps (<10 m resolution), national land cover maps (25 m) and European land cover maps (100 m). There were differences of −59·1%, +12·4% and −2·4% in tree cover compared with global (30 m resolution), European (25 m) and national (1 m) estimates. Waveform lidar captured sub‐canopy structure and detected empty spaces in the understorey which contributed a 16% bias in the total green volume derived from non‐waveform lidar observations.

We conclude that waveform lidar has a key role to play in estimating important quantitative metrics of urban green infrastructure, which is important because urban greenspace is highly fragmented and shows high levels of spatial and volumetric heterogeneity.
Comparison of markers predicting litter size in different pig breeds
Authors: Kwon W.‐S. , Rahman M. S. , Ryu D.‐Y. , Khatun A. , Pang M.‐G.
Published: April 2017

To overcome the limitations of conventional analysis of male fertility in animals and humans, proteomic studies have been performed to develop fertility‐related biomarkers for prognosis and diagnosis of male fertility. However, the studies were focused on specific species or breeds. Therefore, a study is required to validate whether fertility‐related markers would apply to other breeds in pigs. In this study, previously developed fertility‐related biomarkers from Landrace were validated to use for prognosis of male fertility in commercially available breeds. Expression level of eight biomarkers in non‐capacitated and capacitated (C) spermatozoa from Yorkshire and Duroc boars was analyzed. And then, to explore the validity of these markers for prognosis of male fertility, i.e. litter size, artificial insemination was performed. Among them, RAB2A (NC) and UQCRC1 (NC) turned out to be highest efficient markers for Yorkshire. RAB2A (C) was most efficient marker for Duroc. Average litter size has increased as much as 1.41 live born after prediction using eight fertility‐related biomarkers in Yorkshire. In addition, average 2.52 litter size was increased after prediction using eight fertility‐related biomarkers in Duroc. Average litter sizes were especially highly increased after prediction of fertility using RAB2A (NC) in Yorkshire (1.57 piglets) and TPI (NC) in Duroc (3.14 piglets), respectively. As a result, all biomarkers were significantly correlated with litter size. However, overall accuracy to predict litter size in three breeds was different in response with each marker. Average litter size after artificial insemination was also significantly affected by marker selection. Therefore, this study suggests that developed fertility‐related markers may be used for prognosis and diagnosis of male fertility irrespective of breed. However, selection of efficient markers for breeds should be considered to obtain more accurate and efficient outcomes.
Therapeutic protein deimmunization by T‐cell epitope removal: antigen‐specific immune responses in vitro and in vivo
Authors: Asgari Saeme , Ebrahim‐Habibi Azadeh , Mahdavi Mehdi , Choopani Mohammad , Mirzahoseini Hasan
Published: April 2017

Hirudin III is an effective anti‐coagulant; however, in 40% of treated patients, a high‐titer of anti‐Hirudin III IgG antibodies is observed. Development of antibody responses requires the activation of helper T lymphocyte (HTL), which is dependent on peptide epitopes binding to HLA class II molecules. Based on computational prediction softwares, four new mutants of Hirudin III, T4K, S9G, V21G, and V21K, had been designed with the aim of reducing the binding affinity of these HTL epitopes. The constructed mutants have been purified and assayed for bioactivity. Finally in vitro and in vivo cell‐mediated responses were assessed and humoral immune assays were performed. All modified forms of Hirudin III were active, and showed significantly reduced human T‐cell responses. All mutants indicated lower human IFN‐γ level compared to native Hirudin, and V21K indicated lowest IFN‐γ level. Mice immunized with T4K and V21K showed a significant reduction in total antibody responses and mouse IFN‐γ levels. Mice immunized with V21K after 3rd immunization had lower T‐cell proliferation compared to native Hirudin and other mutants. Based on these results, V21K is proposed as the best alternate Hirudin III candidate with lowest antigenicity. These findings validate our rational design strategy aimed at providing new active analogs of therapeutic proteins with reduced immunogenicity.
Editorial: inflammatory bowel disease risk reduction after migration – are early life events important?
Authors: Lamba M. J. , Tharayil V. S. , Gearry R. B.
Published: April 2017

Linked Content

This article is linked to Hammer et al paper. To view this article visit https://doi.org/10.1111/apt.13975.
Editorial: accumulating data about ustekinumab in refractory Crohn's disease in real world experience
Authors: Khorrami S. , Gisbert J. P.
Published: April 2017

Linked Content

This article is linked to Ma et al paper. To view this article visit https://doi.org/10.1111/apt.14016.
Evaluating the Quality of the Deliberation in Moral Case Deliberations: A Coding Scheme
Authors: Jellema Hylke , Kremer Swanny , Mackor Anne‐Ruth , Molewijk Bert
Published: April 2017

Moral Case Deliberation (MCD) is an up and coming form of ethics support wherein clinical professionals deliberate about moral questions they face in their work. So far, it has been unclear what quality of deliberation in MCD is entailed and how to evaluate this quality. This article proposes a coding scheme that fits the theoretical background of MCD and allows researchers to evaluate the quality of the deliberation in MCDs. We consider deliberation in MCD to be of good quality when participants enrich their own understanding of a case by being exposed to the viewpoints of others. In order to have such an enriching effect, the deliberation in an MCD ought to involve different kinds of arguments from the perspectives of different stakeholders and in favour of different resolutions to the case; and the process of deliberation ought to be critical but constructive.
Evaluating Clinical Ethics Support: A Participatory Approach
Authors: Metselaar Suzanne , Widdershoven Guy , Porz Rouven , Molewijk Bert
Published: April 2017

The current process towards formalization within evaluation research, in particular the use of pre‐set standards and the focus on predefined outcomes, implies a shift of ownership from the people who are actually involved in real clinical ethics support services (CESS) in a specific context to external stakeholders who increasingly gain a say in what ‘good CESS’ should look like. The question is whether this does justice to the insights and needs of those who are directly involved in actual CESS practices, be it as receivers or providers. We maintain that those actually involved in concrete CESS practices should also be involved in its evaluation, not only as respondents, but also in setting the agenda of the evaluation process and in articulating the criteria by which CESS is evaluated. Therefore, we propose a participatory approach to CESS evaluation. It focuses on (1) the concrete contexts in which CESS takes place, (2) reflective and dialogical learning processes, and (3) how to be democratic and inclusive. In particular, this approach to CESS evaluation is akin to realist evaluation, dialogical evaluation, and responsive evaluation. An example of a participatory approach to evaluating CESS is presented and some critical issues concerning this approach are discussed.
What Outcomes do Dutch Healthcare Professionals Perceive as Important Before Participation in Moral Case Deliberation?
Authors: de Snoo‐Trimp Janine , Widdershoven Guy , Svantesson Mia , de Vet Riekie , Molewijk Bert
Published: April 2017

Background

There has been little attention paid to research on the outcomes of clinical ethics support (CES) or critical reflection on what constitutes a good CES outcome. Understanding how CES users perceive the importance of CES outcomes can contribute to a better understanding, use of and normative reflection on CES outcomes.

Objective

To describe the perceptions of Dutch healthcare professionals on important outcomes of moral case deliberation (MCD), prior to MCD participation, and to compare results between respondents.

Methods

This mixed‐methods study used both the Euro‐MCD instrument and semi‐structured interviews. Healthcare professionals who were about to implement MCD were recruited from nursing homes, hospitals, psychiatry and mentally disabled care institutions.

Results

331 healthcare professionals completed the Euro‐MCD instrument, 13 healthcare professionals were interviewed. The outcomes perceived as most important were ‘more open communication’, ‘better mutual understanding’, ‘concrete actions’, ‘see the situation from different perspectives’, ‘consensus on how to manage the situation’ and ‘find more courses of action’. Interviewees also perceived improving quality of care, professionalism and the organization as important. Women, nurses, managers and professionals in mentally disabled care rated outcomes more highly than other respondents.

Conclusions

Dutch healthcare professionals perceived the MCD outcomes related to collaboration as most important. The empirical findings can contribute to shared ownership of MCD and a more specific use of MCD in different contexts. They can inform international comparative research on different CES types and contribute to normative discussions concerning CES outcomes. Future studies should reflect upon important MCD outcomes after having experienced MCD.
Selective and state‐dependent activation of TRESK (K2P18.1) background potassium channel by cloxyquin
Authors: Lengyel Miklós , Dobolyi Alice , Czirják Gábor , Enyedi Péter
Published: April 2017

Background and Purpose

Cloxyquin (5‐cloroquinolin‐8‐ol) has been described as an activator of TRESK (K2P18.1, TWIK‐related spinal cord K+ channel) background potassium channel. We have examined the specificity of the drug by testing several K2P channels. We have investigated the mechanism of cloxyquin‐mediated TRESK activation, focusing on the differences between the physiologically relevant regulatory states of the channel.

Experimental Approach

Potassium currents were measured by two‐electrode voltage clamp in Xenopus oocytes and by whole‐cell patch clamp in mouse dorsal root ganglion (DRG) neurons.

Key Results

Cloxyquin (100 µM) activated mouse and human TRESK 4.4 ± 0.3 (n = 28) and 3.9 ± 0.3‐fold (n = 8), respectively. The drug selectively targeted TRESK in the K2P channel family and exerted state‐dependent effects. TRESK was potently activated by cloxyquin in the resting state. However, after robust activation of the current by the calcium signal, evoked by stimulation of Gq‐coupled receptors, the compound did not influence mouse TRESK and only slightly affected the human channel. The constitutively active mutant channels, mimicking the dephosphorylated state (S276A) or containing altered channel pore (F156A and F364A), were not further stimulated by cloxyquin. In a subpopulation of isolated DRG neurons, cloxyquin substantially activated the background potassium current.

Conclusions and Implications

Cloxyquin activates TRESK by a Ca2+/calcineurin‐independent mechanism. The drug is specific for TRESK within the K2P channel family and useful for studying TRESK currents in native cells. The state‐dependent pharmacological profile of this channel should be considered in the development of therapeutics for migraine and other nociceptive disorders.
Head‐to‐head comparison of structurally unrelated dipeptidyl peptidase 4 inhibitors in the setting of renal ischemia reperfusion injury
Authors: Reichetzeder Christoph , von Websky Karoline , Tsuprykov Oleg , Mohagheghi Samarin Azadeh , Falke Luise Gabriele , Dwi Putra Sulistyo Emantoko , Hasan Ahmed Abdallah , Antonenko Viktoriia , Curato Caterina , Rippmann Jörg , Klein Thomas , Hocher Berthold
Published: April 2017

Background and Purpose

Results regarding protective effects of dipeptidyl peptidase 4 (DPP4) inhibitors in renal ischaemia–reperfusion injury (IRI) are conflicting. Here we have compared structurally unrelated DPP4 inhibitors in a model of renal IRI.

Experimental Approach

IRI was induced in uninephrectomized male rats by renal artery clamping for 30 min. The sham group was uninephrectomized but not subjected to IRI. DPP4 inhibitors or vehicle were given p.o. once daily on three consecutive days prior to IRI: linagliptin (1.5 mg·kg−1·day−1), vildagliptin (8 mg·kg−1·day−1) and sitagliptin (30 mg·kg−1·day−1). An additional group received sitagliptin until study end (before IRI: 30 mg·kg−1·day−1; after IRI: 15 mg·kg−1·day−1).

Key Results

Plasma‐active glucagon‐like peptide type 1 (GLP‐1) increased threefold to fourfold in all DPP4 inhibitor groups 24 h after IRI. Plasma cystatin C, a marker of GFR, peaked 48 h after IRI. Compared with the placebo group, DPP4 inhibition did not reduce increased plasma cystatin C levels. DPP4 inhibitors ameliorated histopathologically assessed tubular damage with varying degrees of drug‐specific efficacies. Renal osteopontin expression was uniformly reduced by all DPP4 inhibitors. IRI‐related increased renal cytokine expression was not decreased by DPP4 inhibition. Renal DPP4 activity at study end was significantly inhibited in the linagliptin group, but only numerically reduced in the prolonged/dose‐adjusted sitagliptin group. Active GLP‐1 plasma levels at study end were increased only in the prolonged/dose‐adjusted sitagliptin treatment group.

Conclusions and Implications

In rats with renal IRI, DPP4 inhibition did not alter plasma cystatin C, a marker of glomerular function, but may protect against tubular damage.
The isoprenoid derivative N6‐benzyladenosine CM223 exerts antitumor effects in glioma patient‐derived primary cells through the mevalonate pathway
Authors: Ciaglia Elena , Grimaldi Manuela , Abate Mario , Scrima Mario , Rodriquez Manuela , Laezza Chiara , Ranieri Roberta , Pisanti Simona , Ciuffreda Pierangela , Manera Clementina , Gazzerro Patrizia , D'Ursi Anna Maria , Bifulco Maurizio
Published: April 2017

Background and Purpose

N6‐Isopentenyladenosine (i6A) is a modified nucleoside exerting in vitro and in vivo antiproliferative effects. We previously demonstrated that the actions of i6A correlate with the expression and activity of farnesyl pyrophosphate synthase (FPPS), a key enzyme involved in the mevalonate (MVA) pathway, which is aberrant in brain cancer. To develop new anti‐glioma strategies, we tested related compounds exhibiting greater activity than i6A.

Experimental Approach

We designed and synthesized i6A derivatives characterized by the introduction of diverse chemical moieties in the N6 position of adenosine and tested for their efficacy in U87 cells and in primary glioma cultures, derived from patients. NMR‐based structural analysis, molecular docking calculations and siRNA mediated knockdown were used to clarify the molecular basis of their action, targeting FPPS protein.

Key Results

CM223, the i6A derivative including a benzyl moiety in N6 position of adenine, showed marked activity in selectively targeting glioma cells, but not normal human astrocytes. This was due to induction of intrinsic pathways of apoptosis and inhibition of proliferation, along with blockade of FPPS‐dependent protein prenylation, which counteracted oncogenic signalling mediated by EGF receptors.

Conclusion and Implications

The biological effects together with structural data on interaction of CM223 with FPPS, provided additional evidence for the correlation of the i6A/CM223 antitumor activity with FPPS modulation. Because the MVA pathway is an important promising target, CM223 and its derivatives should be considered interesting active molecules in antiglioma research.
Rho GDP‐dissociation inhibitor α is a potential prognostic biomarker and controls telomere regulation in colorectal cancer
Authors: Huang Dandan , Lu Weisi , Zou Shaomin , Wang Huaiming , Jiang Yuanling , Zhang Xiya , Li Pengqing , Songyang Zhou , Wang Lei , Wang Jianping , Huang Junjiu , Fang Lekun
Published: April 2017

Rho GDP‐dissociation inhibitor α (RhoGDIα) is an essential regulator for Rho GTPases. Although RhoGDIα may serve as an oncogene in colorectal cancer (CRC), the underlying mechanism is still unclear. We investigated the function, mechanism, and clinical significance of RhoGDIα in CRC progression. We founded that downregulation of RhoGDIα repressed CRC cell proliferation, motility, and invasion. Overexpression of RhoGDIα increased DNA damage response signals at telomeres, and led to telomere shortening in CRC cells, also being validated in 26 pairs of CRC tissues. Mechanistic studies revealed that RhoGDIα could promote telomeric repeat factor 1 (TRF1) expression through the phosphatidylinositol 3‐kinase–protein kinase B signal pathway. Moreover, RhoGDIα protein levels were strongly correlated with TRF1 in CRC tissues. A cohort of 297 CRC samples validated the positive relationship between RhoGDIα and TRF1, and revealed that RhoGDIα and TRF1 levels were negatively associated with CRC patients' survival. Taken together, our results suggest that RhoGDIα regulate TRF1 and telomere length and may be novel prognostic biomarkers in colorectal cancer.
Non‐alcoholic fatty liver disease (NAFLD) prevalence and its metabolic associations in patients with type 1 diabetes and type 2 diabetes
Authors: Cusi Kenneth , Sanyal Arun J. , Zhang Shuyu , Hartman Mark L. , Bue‐Valleskey Juliana M. , Hoogwerf Byron J. , Haupt Axel
Published: April 2017

We investigated non‐alcoholic fatty liver disease (NAFLD) prevalence and its metabolic associations in patients with type 1 diabetes (T1D), and in insulin‐naïve and insulin‐treated patients with type 2 diabetes (T2D). Baseline data from patients who had liver fat content (LFC) evaluated by magnetic resonance imaging in four phase 3 studies of basal insulin peglispro (BIL) were analysed. Associations of NAFLD with clinical characteristics, glycaemic control and diabetes therapy were evaluated. The prevalence of NAFLD (defined as LFC ≥ 6%) was low in T1D (8.8%) but high in T2D, with greater prevalence in insulin‐naïve (75.6%) vs insulin‐treated (61.7%) T2D patients. LFC (mean ± SD) was higher in T2D patients (insulin‐naïve, 13.0% ± 8.4%; insulin‐treated, 10.2% ± 7.8%) than in T1D patients (3.2% ± 3.2%). In T2D, NAFLD was associated with several markers of insulin resistance. In all three populations, there was an absence of association of HbA1c with LFC, but insulin doses were higher in patients with NAFLD.
Public Credit Programmes and Firm Performance in Brazil
Authors: Maffioli Alessandro , de Negri Joao A. , Rodriguez Cesar M. , Vazquez‐Bare Gonzalo
Published: April 2017

Credit rationing is a common phenomenon faced by firms, one that has negative implications for long‐term investments. In Brazil, public credit plays a key role in supporting firms: state‐owned banks account for almost half of the outstanding credit. Public credit programmes aim at reducing credit restrictions, increasing competitiveness and job creation for small and medium enterprises. This article analyzes the effectiveness of the credit lines managed by two main public institutions in Brazil. Results show that access to public credit lines has a significant positive impact on firms’ employment growth and exports, while no effect was found on wage differential. The impact on exports is driven by the increase in volumes among exporting firms rather than the probability of becoming an exporter.
Not so different from non‐traders
Authors: Francis David C. , Schweiger Helena
Published: April 2017

This paper uses a unique, comparable firm‐level dataset covering more than 80 developing middle‐income economies to provide a novel set of stylized facts on firms engaging in international trade, focusing on the Middle East and North Africa (MENA) region. We show that firms in MENA are more likely to export and/or import than their counterparts elsewhere. However, we only find the expected positive and significant productivity premia for exporters outside of MENA. While MENA's larger exporters are indeed more productive than non‐exporters, a large share of exporters – the comparatively low‐volume ones – are not. We also confirm positive and significant size and productivity premia for manufacturers that import only, with productivity premia in MENA at least double of those in middle‐income economies elsewhere. In contrast, we find no size or productivity premia for MENA's manufacturers that export, but do not import. These patterns are consistent with substantial distortions in the relative fixed and variable costs of trading, likely a reflection of selectively applied policies.
Pious populists at the gate
Authors: Meyersson Erik
Published: April 2017

In this paper, I evaluate the economic track record of the Justice and Development Party (AKP) in Turkey, using the synthetic control method (SCM). This methodology compares the post‐AKP development trajectory of Turkey with that of a weighted combination of similar but untreated countries. The SCM is particularly useful in this setting as it allows construction of a synthetic control to Turkey that replicates the pre‐AKP development dynamics. I find that Turkey under AKP grew no faster in terms of GDP per capita when compared with a synthetic counterpart from a wide pool of other countries. Restricting the pool of control units to only include Muslim countries shows Turkey growing slower than its Muslim counterparts. Moreover, analysis of post‐crisis recovery periods shows Turkey growing no faster than comparable post‐crisis cases across time. However, expanding the outcome set to health and education reveals large positive differences in both infant and maternal mortality as well as university enrolment, consistent with stated AKP policies to improve access to health and education sectors for the relatively poorer segments of the population. Nonetheless, increased access in these fields is not matched by improved labour market access, as both labour force participation as well as unemployment have deteriorated, and especially so for women. As for measures of institutions, I fail to find any durable positive differences in measures related to democracy or human rights early on during the post‐intervention period, and in several instances there is evidence of significant declines over the long run. A particularly salient feature of the AKP's reign is reduced political power of the military, consistent with the military in Turkey receiving lower economic rents than its synthetic counterpart during AKP's reign.
Barriers and facilitators to implementing family support and education in Early Psychosis Intervention programmes: A systematic review
Authors: Selick Avra , Durbin Janet , Vu Nhi , O'Connor Karen , Volpe Tiziana , Lin Elizabeth
Published: April 2017

Family support is a core component of the Early Psychosis Intervention (EPI) model, yet it continues to have relatively low rates of implementation in practice. This paper reports results of a literature review on facilitators and barriers to delivering family interventions in EPI programmes. A search was conducted of 4 electronic databases, Medline, EMBASE, PsycINFO and Joanna Briggs, from 2000 to 2015 using terms related to early onset psychosis, family work and implementation. Four thousand four hundred and two unique studies were identified, 7 of which met inclusion criteria. Barriers and facilitators were coded and aggregated to higher‐level themes using a consensus approach. Five of 7 studies examined structured multifamily psychoeducation. Uptake by families was affected by: family/client interest and readiness to participate; ability to access supports; and support needs/preferences. Implementation by programmes was affected by staff access to training and resources to provide family support. A key finding across the identified studies was that families have different needs and preferences regarding the timing, length, intensity and content of the intervention. One size does not fit all and many families do not require the intensive psychoeducational programmes typically provided. The reviewed literature suggests that flexible, tiered approaches to care may better meet family needs and increase rates of uptake of family support. However, more research is needed on the effectiveness of different models of family support in early psychosis and how they can be successfully implemented.
Sexual selection reinforces a higher flight endurance in urban damselflies
Authors: Tüzün Nedim , Op de Beeck Lin , Stoks Robby
Published: April 2017

Urbanization is among the most important and globally rapidly increasing anthropogenic processes and is known to drive rapid evolution. Habitats in urbanized areas typically consist of small, fragmented and isolated patches, which are expected to select for a better locomotor performance, along with its underlying morphological traits. This, in turn, is expected to cause differentiation in selection regimes, as populations with different frequency distributions for a given trait will span different parts of the species’ fitness function. Yet, very few studies considered differentiation in phenotypic traits associated with patterns in habitat fragmentation and isolation along urbanization gradients, and none considered differentiation in sexual selection regimes. We investigated differentiation in flight performance and flight‐related traits and sexual selection on these traits across replicated urban and rural populations of the scrambling damselfly Coenagrion puella. To disentangle direct and indirect paths going from phenotypic traits over performance to mating success, we applied a path analysis approach. We report for the first time direct evidence for the expected better locomotor performance in urban compared to rural populations. This matches a scenario of spatial sorting, whereby only the individuals with the best locomotor abilities colonize the isolated urban populations. The covariation patterns and causal relationships among the phenotypic traits, performance and mating success strongly depended on the urbanization level. Notably, we detected sexual selection for a higher flight endurance only in urban populations, indicating that the higher flight performance of urban males was reinforced by sexual selection. Taken together, our results provide a unique proof of the interplay between sexual selection and adaptation to human‐altered environments.
Attribution of seasonal leaf area index trends in the northern latitudes with “optimally” integrated ecosystem models
Authors: Zhu Zaichun , Piao Shilong , Lian Xu , Myneni Ranga B. , Peng Shushi , Yang Hui
Published: April 2017

Significant increases in remotely sensed vegetation indices in the northern latitudes since the 1980s have been detected and attributed at annual and growing season scales. However, we presently lack a systematic understanding of how vegetation responds to asymmetric seasonal environmental changes. In this study, we first investigated trends in the seasonal mean leaf area index (LAI) at northern latitudes (north of 30°N) between 1982 and 2009 using three remotely sensed long‐term LAI data sets. The most significant LAI increases occurred in summer (0.009 m2 m−2 year−1, p < .01), followed by autumn (0.005 m2 m−2 year−1, p < .01) and spring (0.003 m2 m−2 year−1, p < .01). We then quantified the contribution of elevating atmospheric CO2 concentration (eCO2), climate change, nitrogen deposition, and land cover change to seasonal LAI increases based on factorial simulations from 10 state‐of‐the‐art ecosystem models. Unlike previous studies that used multimodel ensemble mean (MME), we used the Bayesian model averaging (BMA) to optimize the integration of model ensemble. The optimally integrated ensemble LAI changes are significantly closer to the observed seasonal LAI changes than the traditional MME results. The BMA factorial simulations suggest that eCO2 provides the greatest contribution to increasing LAI trends in all seasons (0.003–0.007 m2 m−2 year−1), and is the main factor driving asymmetric seasonal LAI trends. Climate change controls the spatial pattern of seasonal LAI trends and dominates the increase in seasonal LAI in the northern high latitudes. The effects of nitrogen deposition and land use change are relatively small in all seasons (around 0.0002 m2 m−2 year−1 and 0.0001–0.001 m2 m−2 year−1, respectively). Our analysis of the seasonal LAI responses to the interactions between seasonal changes in environmental factors offers a new perspective on the response of global vegetation to environmental changes.
Investigation of Arsenotrophic Microbiome in Arsenic‐Affected Bangladesh Groundwater
Authors: Sultana Munawar , Mou Taslin Jahan , Sanyal Santonu Kumar , Diba Farzana , Mahmud Zahid Hayat , Parvez Anowar Khasru , Hossain M. Anwar
Published: April 2017

Arsenotrophic bacteria contribute to the nutrient cycling in arsenic (As) affected groundwater. This study employed a culture‐independent and ‐dependent investigation of arsenotrophic microbiomes in As affected groundwater samples collected from Madhabpur, Sonatengra, and Union Porishod in Singair Upazila, Manikganj, Bangladesh. Total As contents, detected by Atomic Absorption Spectrophotometry (AAS) of the samples, were 47 µg/L (Madhabpur, SNGW‐1), 53 µg/L (Sonatengra, SNGW‐2), and 12 µg/L (Union porishod, SNGW‐3), whereas the control well (SNGW‐4; depths >150 m) showed As content of 6 µg/L. Denaturing Gradient Gel Electrophoresis (DGGE) analysis of the amplified 16S rRNA gene from As‐affected groundwater samples revealed the dominance of aerobic bacteria Pseudomonas within heterogeneous bacterial populations. DGGE of heterotrophic enrichments supplemented with arsenite [As (III)] for 4 weeks showed the dominance of Chryseobacterium, Flavobacterium, and Aquabacterium, whereas the dominant genera in that of autotrophic enrichments were Aeromonas, Acinetobacter, and Pseudomonas. Cultured bacteria retrieved from both autotrophic and heterotrophic enrichments were distinguished into nine genotypes belonging to Chryseobacterium, Acinetobacter, Escherichia, Pseudomonas, Stenotrophomonas, Janibacter, Staphylococcus, and Bacillus. They exhibited varying range of As(III) tolerance from 4 to 27 mM. As(III) transformation potential was confirmed within the isolates with oxidation rate as high as 0.143 mM/h for Pseudomonas sp. Sn 28. The arsenotrophic microbiome specifies their potential role in groundwater As‐cycling and their genetic information provide the scientific basis for As‐bioremediation.
Physical function was related to mortality in patients with chronic kidney disease and dialysis
Authors: Morishita Shinichiro , Tsubaki Atsuhiro , Shirai Nobuyuki
Published: April 2017

Previous studies have shown that exercise improves aerobic capacity, muscular functioning, cardiovascular function, walking capacity, and health‐related quality of life (QOL) in patients with chronic kidney disease (CKD) and dialysis. Recently, additional studies have shown that higher physical activity contributes to survival and decreased mortality as well as physical function and QOL in patients with CKD and dialysis. Herein, we review the evidence that physical function and physical activity play an important role in mortality for patients with CKD and dialysis. During November 2016, Medline and Web of Science databases were searched for published English medical reports (without a time limit) using the terms “CKD” or “dialysis” and “mortality” in conjunction with “exercise capacity,” “muscle strength,” “activities of daily living (ADL),” “physical activity,” and “exercise.” Numerous studies suggest that higher exercise capacity, muscle strength, ADL, and physical activity contribute to lower mortality in patients with CKD and dialysis. Physical function is associated with mortality in patients with CKD and dialysis. Increasing physical function may decrease the mortality rate of patients with CKD and dialysis. Physicians and medical staff should recognize the importance of physical function in CKD and dialysis. In addition, exercise is associated with reduced mortality among patients with CKD and dialysis.