bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inosine Strongly Enhances Proliferation of Human C32 Melanoma Cells through PLC‐PKC‐MEK1/2‐ERK1/2 and PI3K Pathways
Authors: Soares Ana Sofia , Costa Vera Marisa , Diniz Carmen , Fresco Paula 
Published: June 2014

AbstractMalignant melanoma is the most deadly type of skin cancer. The lack of effective pharmacological approaches for this tumour can be related to the incomplete understanding of the pathophysiological mechanisms involved in melanoma cell proliferation. Adenosine has growth‐promoting and growth inhibitory effects on tumour cells. We aimed to investigate effects of adenosine and its metabolic product, inosine, on human C32 melanoma cells and the signalling pathways involved. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) reduction and bromodeoxyuridine (BrdU) proliferation assays were used to evaluate adenosine, adenosine deaminase and inosine effects, in the absence or presence of adenosine receptor (AR), A3AR and P2Y1R antagonists and PLC, PKC, MEK1/2 and PI3K inhibitors. ERK1/2 levels were determined using an ELISA kit. Adenosine and inosine levels were quantified using an enzyme‐coupled assay. Adenosine caused cell proliferation through AR activation. Adenosine deaminase increased inosine levels (nanomolar concentrations) on the extracellular space, in a time‐dependent manner, inducing proliferation through A3AR activation. Micromolar concentrations of inosine enhanced proliferation through A3AR activation, causing an increase in ERK1/2 levels, and P2Y1R activation via ENT‐dependent mechanisms. We propose the simultaneous activation of PLC‐PKC‐MEK1/2‐ERK1/2 and PI3K pathways as the main mechanism responsible for the proliferative effect elicited by inosine and its significant role in melanoma cancer progression.
Implicit theories about intelligence and growth (personal best) goals: Exploring reciprocal relationships
Authors: Martin Andrew J. 
Published: June 2014

BackgroundThere has been increasing interest in growth approaches to students' academic development, including value‐added models, modelling of academic trajectories, growth motivation orientations, growth mindsets, and growth goals.AimsThis study sought to investigate the relationships between implicit theories about intelligence (incremental and entity theories) and growth (personal best, PB) goals – with particular interest in the ordering of factors across time.SampleThe study focused on longitudinal data of 969 Australian high school students.MethodThe classic cross‐lagged panel design (using structural equation modelling) was employed to shed light on the ordering of Time 1 growth goals, incremental theories, and entity theories relative to Time 2 (1 year later) growth goals, incremental theories, and entity theories.ResultsFindings showed that Time 1 growth goals predicted Time 2 incremental theories (positively) and entity theories (negatively); Time 1 entity and incremental theories negatively predicted Time 2 incremental and entity theories respectively; but, Time 1 incremental theories and entity theories did not predict growth goals at Time 2.ConclusionThis suggests that entity and incremental theories are negatively reciprocally related across time, but growth goals seem to be directionally salient over incremental and entity theories. Implications for promoting growth goals and growth mindsets are discussed.
Safety and diagnostic accuracy of percutaneous biopsy in upper tract urothelial carcinoma
Authors: Huang Steven Y. , Ahrar Kamran , Gupta Sanjay , Wallace Michael J. , Ensor Joe E. , Krishnamurthy Savitri , Matin Surena F. 
Published: June 2014

ObjectiveTo assess the diagnostic accuracy and safety of percutaneous biopsy for upper tract urothelial carcinoma (UTUC).Patients and MethodsFrom 2002 to 2013, 26 upper tract lesions in 24 patients (20 men; median [range] age 67.8 [51.7–85.9] years) were percutaneously biopsied. Analysis was separated based on lesion appearance: (i) mass infiltrating renal parenchyma, (ii) filling defect in the collecting system, (iii) urothelial wall thickening. We tracked immediate complications and tract seeding on follow‐up imaging.ResultsOf the 26 upper tract lesions, 15 (58%) were masses infiltrating the renal parenchyma (mean [range] size 5.4 [1.1–14.0] cm), six (23%) were urothelial wall thickenings (mean [range] size 0.8 [0.4–1.1] cm), and five (19%) were filling defects within the renal pelvis or calyx (mean [range] size 2.7 [1.0–4.6] cm). Definitive diagnosis of UTUC was made by biopsy in 22 of 26 lesions (85%). Biopsy characterised 14 of 15 infiltrative masses and five of five filling defects; biopsy characterised three of six cases of urothelial wall thickening. CT follow‐up was available for 19 patients (73%) at a median (range) of 13.6 (1.0–98.9) months. Three patients (11%) developed recurrence in the nephrectomy bed at 5.6, 9.7, and 29.0 months after biopsy; none were attributed to tract seeding after independent review, because recurrence was remote from the biopsy site.ConclusionPercutaneous biopsy is effective for diagnosis of UTUC, providing tissue diagnosis in 85% of cases. While case reports cite a risk of tract seeding, no cases of recurrence were definitely attributable to percutaneous biopsy. Thus, for upper tract urothelial lesions, which are not amenable to endoscopic biopsy, percutaneous biopsy is a safe and effective technique.
Ipsilateral renal function preservation after robot‐assisted partial nephrectomy (RAPN): an objective analysis using mercapto‐acetyltriglycine (MAG3) renal scan data and volumetric assessment
Authors: Zargar Homayoun , Akca Oktay , Autorino Riccardo , Brandao Luis Felipe , Laydner Humberto , Krishnan Jayram , Samarasekera Dinesh , Stein Robert J. , Kaouk Jihad H. 
Published: June 2014

ObjectiveTo objectively assess ipsilateral renal function (IRF) preservation and factors influencing it after robot‐assisted partial nephrectomy (RAPN).Patients and MethodsOur database was queried to identify patients who had undergone RAPN from 2007 to 2013 and had complete pre‐ and postoperative mercapto‐acetyltriglycine (MAG3) renal scan assessment. The estimated glomerular filtration rate (eGFR) for the operated kidney was calculated by multiplying the percentage of contribution from the renal scan by the total eGFR. IRF preservation was defined as a ratio of the postoperative eGFR for the operated kidney to the preoperative eGFR for the operated kidney. The percentage of total eGFR preservation was calculated in the same manner (postoperative eGFR/preoperative eGFR × 100). The amount of healthy rim of renal parenchyma removed was assessed by deducting the volume of tumour from the volume of the PN specimen assessed on pathology. Multivariable linear regression was used for analysis.ResultsIn all, 99 patients were included in the analysis. The overall median (interquartile range) total eGFR preservation and IRF preservation for the operated kidney was 83.83 (75.2–94.1)% and 72 (60.3–81)%, respectively (P < 0.01). On multivariable analysis, volume of healthy rim of renal parenchyma removed, warm ischaemia time (WIT) > 30 min, body mass index (BMI) and operated kidney preoperative eGFR were predictive of IRF preservation.ConclusionsUsing total eGFR tends to overestimate the degree of renal function preservation after RAPN. This is particularly relevant when studying factors affecting functional outcomes after nephron‐sparing surgery. IRF may be a more precise assessment method in this setting. Operated kidney baseline renal function, BMI, WIT >30 min, and amount of resected healthy renal parenchyma represent the factors with a significant impact on the IRF preservation. RAPN provides significant preservation of renal function as shown by objective assessment criteria.
Molecular determinants for the high constitutive activity of the human histamine H4 receptor: functional studies on orthologues and mutants
Authors: Wifling D , Löffel K , Nordemann U , Strasser A , Bernhardt G , Dove S , Seifert R , Buschauer A 
Published: June 2014

Background and PurposeSome histamine H4 receptor ligands act as inverse agonists at the human H4 receptor (hH4R), a receptor with exceptionally high constitutive activity, but as neutral antagonists or partial agonists at the constitutively inactive mouse H4 receptor (mH4R) and rat H4 receptor (rH4R). To study molecular determinants of constitutive activity, H4 receptor reciprocal mutants were constructed: single mutants: hH4R‐F169V, mH4R‐V171F, hH4R‐S179A, hH4R‐S179M; double mutants: hH4R‐F169V+S179A, hH4R‐F169V+S179M and mH4R‐V171F+M181S.Experimental ApproachSite‐directed mutagenesis with pVL1392 plasmids containing hH4 or mH4 receptors were performed. Wild‐type or mutant receptors were co‐expressed with Gαi2 and Gβ1γ2 in Sf9 cells. Membranes were studied in saturation and competition binding assays ([3H]‐histamine), and in functional [35S]‐GTPγS assays with inverse, partial and full agonists of the hH4 receptor.Key ResultsConstitutive activity decreased from the hH4 receptor via the hH4R‐F169V mutant to the hH4R‐F169V+S179A and hH4R‐F169V+S179M double mutants. F169 alone or in concert with S179 plays a major role in stabilizing a ligand‐free active state of the hH4 receptor. Partial inverse hH4 receptor agonists like JNJ7777120 behaved as neutral antagonists or partial agonists at species orthologues with lower or no constitutive activity. Some partial and full hH4 receptor agonists showed decreased maximal effects and potencies at hH4R‐F169V and double mutants. However, the mutation of S179 in the hH4 receptor to M as in mH4 receptor or A as in rH4 receptor did not significantly reduce constitutive activity.Conclusions and ImplicationsF169 and S179 are key amino acids for the high constitutive activity of hH4 receptors and may also be of relevance for other constitutively active GPCRs.Linked ArticlesThis article is part of a themed issue on Histamine Pharmacology Update published in volume 170 issue 1. To view the other articles in this issue visit http://onlinelibrary.wiley.com/doi/10.1111/bph.2013.170.issue-1/issuetoc
Childhood maltreatment and executive functions in adolescents
Authors: Mothes Luiza , Kristensen Christian Haag , Grassi‐Oliveira Rodrigo , Fonseca Rochele Paz , de Lima Argimon Irani Iracema , Irigaray Tatiana Quarti 
Published: June 2014

BackgroundThe aim of this study was to investigate differences in executive functions between adolescents exposed to different forms of single‐ and multitype childhood maltreatment.MethodThe sample was composed of 83 adolescents, divided into three groups: single‐type maltreatment (n = 24), multitype maltreatment (n = 19), and no history of maltreatment (n = 40), matched for education and sex.ResultsThe results showed that teenagers who suffered a single type of childhood maltreatment performed worse than the other two groups on tasks of cognitive flexibility and visual processing speed. Individuals who suffered multitype maltreatment had worse initiation and lower verbal processing speed than the other two groups.ConclusionsChildhood maltreatment may have a significant impact on executive functioning in adolescence.
Encouraging entrepreneurship with innovation vouchers: Recent experience, lessons, and research directions
Authors: Langhorn K. 
Published: June 2014

AbstractInnovation vouchers are widely used internationally by governments to support emerging small business. Traditionally, vouchers were used to subsidize social benefits such as food, education or health services, but are increasingly used to stimulate entrepreneurial effort. Innovation vouchers are usually given to small firms to subsidize the cost of business or technical services from external providers. This enables the company to have more control over their development activities, while sustaining the external service providers. International and Canadian experience suggests considerable congruence in program design but, in some settings, special features have been devised to address local business needs and development priorities. A largely untapped body of evidence could be used to assess the impact of this tool and opportunities for refinement and application.SommaireLes coupons pour l'innovation sont largement utilisés par les gouvernements à l'échelle internationale afin de soutenir les petites entreprises émergentes. Traditionnellement, les coupons étaient utilisés pour subventionner les avantages sociaux comme les repas, l'éducation ou les services de santé, mais ils servent de plus en plus à stimuler l'effort entrepreneurial. Les coupons pour l'innovation sont habituellement donnés à de petites entreprises afin de subventionner les coûts d'affaires ou les services techniques des fournisseurs externes. Cela permet à l'entreprise de mieux contrôler ses activités de développement, tout en maintenant les fournisseurs de services externes. L'expérience internationale et canadienne laisse entendre une remarquable congruence dans la conception des programmes, mais dans certains milieux, des caractéristiques spéciales ont été conçues pour répondre aux besoins des entreprises locales et aux priorités de développement. Un ensemble de données disponibles essentiellement non exploité pourrait être utilisé pour évaluer l'impact de cet outil et les possibilités d'amélioration et d'application.
Discovery of Novel 17‐Phenylethylaminegeldanamycin Derivatives as Potent Hsp90 Inhibitors
Authors: Li Zhenyu , Jia Lejiao , Wang Jifeng , Wu Xingkang , Shi Guowei , Lu Chunhua , Shen Yuemao 
Published: June 2014

Twenty‐six 17‐phenylethylamine‐modified geldanamycin derivatives were synthesized and evaluated for antiproliferation activity in human cancer cell lines, LNCaP and MDA‐MB‐231. Five derivatives (2j, 2q, 2v, 2x, and 2y) showed excellent in vitro antitumor activities. Among them, compound 2y was the most potent lead, with IC50 values of 0.27 ± 0.11 and 0.86 ± 0.23 μm for LNCaP and MDA‐MB‐231, respectively. In particular, compound 2y was more active than its precursor geldanamycin against LNCap cells. Liver injury test in mice demonstrated that 2y group showed no significant difference for serum alanine aminotransferase (ALT) activity versus vehicle control, indicating that 2y was a promising antitumor candidate. Preliminary structure–activity relationship (SAR) and molecular dynamics (MD) simulations of this new series of geldanamycin derivatives were also investigated, suggesting a theoretical model of 17‐phenylethylaminegeldanamycins binding to Hsp90.
Physical environments, policies and practices for physical activity and screen‐based sedentary behaviour among preschoolers within child care centres in Melbourne, Australia and Kingston, Canada
Authors: Hinkley T. , Carson V. , Hesketh K. D. 
Published: June 2014

AbstractBackgroundCharacteristics of preschool and child care centres have previously been shown to be associated with children's health behaviours such as physical activity and screen‐based sedentary behaviour. This paper investigates differences in physical environments, policies and practices between child care centres in Melbourne, Australia and Kingston, Canada which may be associated with such behaviours.MethodsAudits of child care centres were undertaken by trained research assistants for the Healthy Active Preschool and Primary Years (Melbourne, Australia; n = 136) study and the Healthy Living Habits in Pre‐School Children (Kingston, Canada; n = 46) study. Twenty‐one of the audit items (nine physical environment; 12 policies and practices) were assessed in both samples. Example items included outdoor play and shaded areas, availability of equipment, physical activity instruction for children and staff, opportunities to use electronic media and staff/child interaction during physical activity time. Analyses were completed using SAS version 9.2.ResultsCompared with Australian centres, a higher per cent of Canadian centres had a formal physical activity policy, reported children sat more frequently for 30 min or more and allowed children to watch television. A higher per cent of Australian centres provided an indoor area for physical activity, shade outdoors and physical activity education to staff. Children in Australian centres had access to more fixed play equipment and spent more time outdoors than in Canadian centres.ConclusionsThese findings may help inform the development of best practice and policy guidelines to enhance opportunities for healthy levels of physical activity and screen‐based sedentary behaviour within child care centres in both countries.
Computer science and parsimony: a reappraisal, with discussion of methods for poorly structured datasets
Authors: Goloboff Pablo A. 
Published: June 2014

AbstractIn recent years, several publications in computer science journals have proposed new heuristic methods for parsimony analysis. This contribution discusses those papers, including methods highly praised by their authors, such as Hydra, Sampars and GA + PR + LS. Trees of comparable or better scores can be obtained using the program TNT, but from one to three orders of magnitude faster. In some cases, the search methods are very similar to others long in use in phylogenetics, but the enormous speed differences seem to correspond more to poor implementations than to actual differences in the methods themselves.
Muscle echo intensity: reliability and conditioning factors
Authors: Caresio Cristina , Molinari Filippo , Emanuel Giorgio , Minetto Marco Alessandro 
Published: June 2014

SummaryObjectiveTo assess the issue of muscle echo intensity reliability and to investigate the relationship between muscle echo intensity and size, shape and location of the region of interest (ROI) used for echo intensity quantification.MethodsUltrasonographic scans of the following five muscles were acquired in twenty healthy subjects: biceps brachii, rectus femoris, vastus lateralis, tibialis anterior and medial gastrocnemius. Muscle echo intensity was quantified in each scan.ResultsWe found that the agreement between the different sized ROIs considered in each scan ranged from moderate (ICC: 0·54) to high (ICC: 0·86) and that the echo intensity consistency between equal sized ROIs of the three scans ranged from low (ICC: 0·42) to very high (0·91). The echo intensity of tibialis anterior and rectus femoris was different between different sized, shaped and located ROIs. The echo intensity of biceps brachii and tibialis anterior was higher than that of all other muscles, and females had higher echo intensity than males. Moreover, the muscle echo intensity was positively correlated with the subcutaneous layer thickness in three of five muscles.ConclusionThe echo intensity reliability was function of the ROI size. Muscle and gender variability in echo intensity was likely due to differences in fibrous and adipose tissue content and distribution. Possible explanations for the observed correlations between muscle echo intensity and subcutaneous layer thickness include the dependence of both variables on total body adiposity or the direct dependence of the extent of intramuscular fat on the amount of subcutaneous fat.
An evaluation of synthetic and natural supravital stains for the cytological examination of dissociated cells in a microfluidic channel
Authors: Mojica W. D. , Bassey R. 
Published: June 2014

ObjectiveAdvances in biotechnology will result in paradigm shifts in both oncology and diagnostics. In pathology, methods such as microfluidics are being explored as delivery tools so that processed cells can serve dual purposes: conventional cytology‐based diagnostics and recovery of the same cells for molecular assays. This wet mount‐based approach to diagnosis will require staining of these cells by supravital dyes. This study was undertaken to determine the optimal supravital stain for the examination of cells in the wet mount preparations present in microfluidic platforms.MethodsCells were dissociated from portions of tissue similar in size to a traditional core biopsy. These tissue‐free cells were separately examined with two synthetic dyes and two natural dyes at varying dilutions.ResultsDifferent dilutions of the synthetic dyes toluidine blue and methylene blue resulted in varying degrees of staining, whereas different dilutions of the natural dyes resulted in fairly constant intensities of colour. These characteristics affected the visualization of cells in wet mount preparations: optimally titered synthetic dyes gave better nuclear detail and cytoplasmic contrast.ConclusionsAll four dyes stained the test cells, but to different degrees and intensities. In our assessment, optimally titered synthetic dyes were better suited to the wet mount approach of microfluidics when compared with natural dyes.
From regionally predictable to locally complex population structure in a freshwater top predator: river systems are not always the unit of connectivity in Northern Pike Esox lucius
Authors: Bekkevold Dorte , Jacobsen Lene , Hemmer‐Hansen Jakob , Berg Søren , Skov Christian 
Published: June 2014

AbstractContemporary genetic diversity is the product of both historical and contemporary forces, such as climatic and geological processes affecting range distribution and continuously moulded by evolutionary forces selection, gene flow and genetic drift. Predatory freshwater fishes, such as Northern Pike Esox lucius, commonly exhibit small population sizes, and several local populations are considered endangered. Pike inhabit diverse habitat types, including lakes, rivers and brackish marine waters, thus spanning from small isolated patches to large open marine systems. However, pike population structure from local to regional scales is relatively poorly described, in spite of its significance to developing conservation measures. We analysed microsatellite variation in a total of 1185 North European pike from 46 samples collected across both local and regional scales, as well as over time, to address two overarching questions: Is pike population structure associated with local and/or regional connectivity patterns, and which factors likely have the main influence on the contemporary distribution of genetic diversity? To answer this, we combined estimators of population diversity and structure to assess evidence of whether populations within (i) habitats, (ii) drainage systems and (iii) geographical regions are closer related than among these ranges, and whether patterns are temporally stable. Contrasting previous predictions that genetic drift obscures signals of postglacial colonisation history, we identified clear regional differences in population genetic signatures, suggesting a major effect of drainage divides on colonisation history and connectivity. However, several populations deviated from the general pattern, showing that local processes may be complex and need to be examined case‐by‐case.