bluuebunny/crossref_metadata_2025 huggingface dataset:
TheC. elegansephrin EFN-4 functions non-cell autonomously with heparan sulfate proteoglycans to promote axon outgrowth and branching
Authors: Schwieterman Alicia A. , Steves Alyse N. , Yee Vivian , Donelson Cory J. , Pital Aaron , Voyles Taylor , Howard Austin M. , Ereddia Danielle E. , Effrein Kelsie S. , McMurry Jonathan L. , Ackley Brian D. , Chisholm Andrew D. , Hudson Martin L.
Published: July 2015

The Eph receptors and their cognate ephrin ligands play key roles in many aspects of nervous system development. These interactions typically occur within an individual tissue type, serving either to guide axons to their terminal targets or to define boundaries between the rhombomeres of the hindbrain. We have identified a novel role for theCaenorhabditis elegansephrin EFN-4 in promoting primary neurite outgrowth in AIY interneurons and D-class motor neurons. Rescue experiments reveal that EFN-4 functions non-cell autonomously in the epidermis to promote primary neurite outgrowth. We also find that EFN-4 plays a role in promoting ectopic axon branching in aC. elegansmodel of X-linked Kallmann syndrome. In this context, EFN-4 functions non-cell autonomously in the body wall muscle, and in parallel with HS biosynthesis genes and HSPG core proteins, which function cell autonomously in the AIY neurons. This is the first report of an epidermal ephrin providing a developmental cue to the nervous system.
Adaptive divergence in the bovine genome
Authors: Barendse William , McWilliam Sean , Bunch Rowan J. , Harrison Blair E.
Published: July 2015

Cattle diverged during the Pleistocene into two subspecies, one in temperate and one in tropical environments. Here we have used next generation sequencing of the indicine subspecies of cattle and compared it to the taurine subspecies. Although 23.8 million single nucleotide polymorphisms (SNP) were found, the number of fixed amino acid substitutions between the taurine and indicine subspecies was low and consistent with the Haldane predictions for adaptive selection rather than with Neutral Theory. We noted 33 regions of enhanced divergence of nonsynonymous SNP between the subspecies, which included an increased rate of deleterious variants. Signals of positive selection were found for genes associated with immunity, including the Bovine Major Histocompatibility Complex, which also showed an increased rate of deleterious amino acid variants. The genes important in sensing the environment, especially the olfactory system, showed a network wide signal of positive selection.
Cancer evolution simulation identifies possible principles underlying intratumor heterogeneity
Authors: Niida Atsushi , Ito Satoshi , Tremmel Georg , Imoto Seiya , Uchi Ryutaro , Takahashi Yusuke , Mimori Koshi , Miyano Satoru
Published: July 2015

Cancer arises from accumulation of somatic mutations and accompanying evolutionary selection for growth advantage. During the evolutionary process, an ancestor clone branches into multiple clones, yielding intratumor heterogeneity. However, principles underlying intratumor heterogeneity have been poorly understood. Here, to explore the principles, we built a cellular automaton model, termed the BEP model, which can reproduce the branching cancer evolution in silico. We then extensively searched for conditions leading to high intratumor heterogeneity by performing simulations with various parameter settings on a supercomputer. Our result suggests that multiple driver genes of moderate strength can shape subclonal structures by positive natural selection. Moreover, we found that high mutation rate and a stem cell hierarchy can contribute to extremely high intratumor heterogeneity, which is characterized by fractal patterns, through neutral evolution. Collectively, This study identified the possible principles underlying intratumor heterogeneity, which provide novel insights into the origin of cancer robustness and evolvability.
Roles of the three L‐domains in β‐retrovirus budding
Authors: Narahara Chisato , Yasuda Jiro
Published: July 2015

Retroviral Gag protein plays a critical role during the late stage of virus budding and possesses a so‐called L‐domain containing PT/SAP, PPxY, YxxL or FPIV motifs that are critical for efficient budding. Mason–Pfizer monkey virus (M‐PMV) contains PSAP, PPPY, and YADL sequences in Gag. This study was performed to investigate the roles of these three L‐domain‐like sequences in virus replication in three different cell lines, 293T, COS‐7 and HeLa cells. It was found that the PPxY motif plays an essential role in progeny virus production as a major L‐domain in all three cell lines. The PSAP sequence was shown to function as an additional L‐domain in HeLa cells and to promote efficient release of M‐PMV; however, this sequence was dispensable for M‐PMV production in 293T and COS‐7 cells, suggesting that the role of the PSAP motif as an L‐domain in M‐PMV budding is cell type‐dependent. Viruses possessing multiple L‐domains appear to change the L‐domain usage to replicate in various cells. On the other hand, the YADL motif was required for M‐PMV production as a transport signal of Gag to the plasma membrane, but not as an L‐domain.
Birds and butterflies respond to soil‐induced habitat heterogeneity in experimental plantings of tallgrass prairie species managed as agroenergy crops in Iowa, USA
Authors: Myers Mark C. , Mason James T. , Hoksch Benjamin J. , Cambardella Cynthia A. , Pfrimmer Jarrett D.
Published: July 2015

The maintenance of habitat heterogeneity in agricultural landscapes has been promoted as a key strategy to conserve biodiversity. Animal response to grassland heterogeneity resulting from spatiotemporal variation in disturbance is well documented; however, the degree to which edaphic variation generates heterogeneity detectable by grassland wildlife has proven more difficult to study in natural settings.

We conducted a field experiment to study how soils directly affect vegetation structure and composition and indirectly affect bird and butterfly assemblages using plantings of tallgrass prairie species managed as agroenergy crops in Iowa, USA. The experimental design included four vegetation treatments of varying species richness replicated on three soil types.

Habitat characteristics varied widely among soils. Crops on sandy loam, the driest, most acidic soil with the lowest nutrient content, developed shorter, less dense vegetation with sparse litter accumulation and more bare ground compared to crops on loam and clay loam.

Birds and butterflies responded similarly to soil‐induced variation in habitat characteristics. Their abundance and species richness were similar on all soils, but their assemblage compositions varied among soils in certain vegetation treatments.

In low‐diversity grass crops, bird assemblages using sandy loam were dominated by species preferring open ground and sparse vegetation for foraging and nesting, whereas assemblages using loam and clay loam were dominated by birds preferring tall, dense vegetation with abundant litter. In high‐diversity prairie crops, the species composition of forbs in bloom varied among soils and strongly influenced butterfly assemblages.

Synthesis and applications. Prairie agroenergy crops established with identical management practices developed variable habitat characteristics due to natural edaphic variation, and this heterogeneity influenced the spatial distribution of bird and butterfly assemblages due to differential habitat use among species. This finding suggests that if unfertilized prairie crops were grown for agroenergy by land managers large‐scale, soil‐induced habitat heterogeneity would promote wildlife diversity within and among fields, further increasing the habitat value of these crops compared to the fertilized, annual monocultures that currently dominate the agricultural landscape. Our study also highlights the need for managers to consider soil properties when selecting sites to restore grassland habitat for species of conservation concern.
Predictors of comorbid polysubstance use and mental health disorders in young adults—a latent class analysis
Authors: Salom Caroline L. , Betts Kim S. , Williams Gail M. , Najman Jackob M. , Alati Rosa
Published: July 2015

Aim

The co‐occurrence of mental health and substance use disorders adds complexity to already‐significant health burdens. This study tests whether mental health disorders group differently across substance use disorder types and compares associations of early factors with the development of differing comorbidities.

Design

Consecutive antenatal clinic attendees were recruited to the longitudinal Mater‐University of Queensland Study of Pregnancy (MUSP). Mother/offspring dyads were followed over 21 years.

Setting

Mater‐Misericordiae Public Hospital, Brisbane, Australia.

Participants

MUSP offspring with maternal baseline information (n = 7223), offspring behaviour data at 14 (n = 4815) and psychiatric diagnoses at 21 (n = 2575).

Measurements

The Composite International Diagnostic Interview yielded life‐time diagnoses of mental health (MH) and substance use (SU) disorders for offspring, then latent class modelling predicted membership of polydisorder groups. We fitted the resulting estimates in multinomial logistic regression models, adjusting for maternal smoking, drinking and mental health, adolescent drinking, smoking and behaviour and mother–child closeness.

Findings

Fit indices [Bayesian information criterion (BIC) = 12 415; Akaike information criterion (AIC) = 12 234] from LCA supported a four‐class solution: low disorder (73.6%), MH/low SU disorder (10.6%), alcohol/cannabis/low MH disorder (12.2%) and poly SU/moderate MH disorder (3.5%). Adolescent drinking predicted poly SU/MH disorders [odds ratio (OR) = 3.34, 95% confidence interval (CI) = 1.42–7.84], while externalizing predicted membership of both SU disorder groups (ORalcohol/cannabis = 2.04, 95% CI = 1.11–3.75; ORpolysubstance = 2.65, 95% CI = 1.1–6.08). Maternal smoking during pregnancy predicted MH (OR = 1.53, 95% CI = 1.06–2.23) and alcohol/cannabis‐use disorders (OR = 1.73; 95% CI = 1.22–2.45). Low maternal warmth predicted mental health disorders only (OR = 2.21, 95% CI = 1.32–3.71).

Conclusions

Mental health disorders are more likely in young adults with polysubstance use disorders than those with alcohol/cannabis use disorders. Predictors of comorbid mental health/polysubstance use disorders differ from those for alcohol/cannabis use disorders, and are detectable during adolescence.
Drug use in Australian nightlife settings: estimation of prevalence and validity of self‐report
Authors: Miller Peter , Curtis Ashlee , Jenkinson Rebecca , Droste Nicolas , Bowe Steven J. , Pennay Amy
Published: July 2015

Aims

This study aimed to (1) estimate the prevalence of illicit drug use in night‐time entertainment districts across five major cities in Australia; and (2) validate self‐reported drug use using biochemical marker oral swabs.

Design

Street intercept surveys and oral drug swabs conducted over a 7‐month period during 2011–12.

Setting

The night‐time entertainment districts of three metropolitan cities (Sydney, Melbourne and Perth) and two regional cities (Wollongong and Geelong) in Australia, between the hours of 10 p.m. and 5 a.m.

Participants

A total of 7581 individuals agreed to participate in the survey (93% response rate). More than half (62%) the sample was male, with a median age of 22 years (range 18–73).

Measurements

Patrons were approached in thoroughfares and while entering and leaving licensed venues. Data collected included demographics and current session alcohol and other substance use. Drug swabs (n = 401) were performed with a subsample of participants.

Findings

Approximately 9% [95% confidence interval (CI) = 7–12%] of participants self‐reported consumption of illicit or non‐prescribed pharmaceutical drugs prior to interview; of those, 81% identified psychostimulants as the drug used. One in five drug swabs returned a positive result, with psychostimulants the most commonly detected drugs (15%; 95% CI = 12–19%). Kappa statistics indicate agreement between self‐report of any illicit drug and a positive drug swab is in the slight range [κ = 0.12 (95% CI = 0.05–0.20) P = 0.000].

Conclusions

Self‐report findings suggest drug use in Australian nightlife is common, although still very much a minority past‐time. Drug swabs indicate a higher prevalence of use (20%) than self‐report (9%), which suggests that self‐reported drug use may not be reliable in this context.
The effect of alcohol outlets, sales and trading hours on alcohol‐related injuries presenting at emergency departments in Perth, Australia, from 2002 to 2010
Authors: Hobday Michelle , Chikritzhs Tanya , Liang Wenbin , Meuleners Lynn
Published: July 2015

Background and Aims

Few studies have investigated the combined effects of alcohol sales, outlet numbers and trading hours on alcohol‐related harms. This study aimed to test whether associations: (i) exist between alcohol‐related emergency department (ED) injuries and alcohol sales and counts of outlets; (ii) vary between on‐ and off‐premises outlets; and (iii) vary by trading hours conditions [extended trading permits (ETP) versus standard hours].

Design

Panel study using 117 postcodes over 8 years (2002–10): 936 data points.

Setting

Perth, Australia.

Participants

ED injury presentations, aggregated to postcode‐level.

Measurements

Alcohol‐related injuries were identified using time‐based surrogate measures: night injuries (n = 51 241) and weekend night injuries (n = 30 682). Measures of alcohol availability included number of outlets with standard and extended trading hours and mean sales per postcode. Negative binomial regression modelling with random effects was used to examine associations between availability and alcohol‐related injury, controlling for socio‐demographic characteristics.

Findings

(i) Night injuries were associated significantly with counts of on‐premises outlets [incident rate ratio (IRR) = 1.046; 95% confidence interval (CI) = 1.014–1.078] and sales per off‐premises outlet (IRR = 1.019; 95% CI = 1.004–1.035); (ii) counts of on‐premises outlets were positively associated with alcohol‐related injury while counts of off‐premises outlets indicated a negative association; and (iii) weekend night injuries increased by about 5% per on‐premises outlet with an ETP (IRR = 1.049; 95% CI = 1.015–1.084) and by less than 1% for outlets with standard trading hours (IRR = 1.008; 95% CI = 1.004–1.013).

Conclusions

Regions of Perth, Australia with greater off‐premises alcohol sales and counts of on‐premises alcohol outlets, particularly those with extended trading hours, appear to have higher levels of alcohol‐related injuries.
Environmental Pollutant Polybrominated Diphenyl Ether, a Flame Retardant, Induces Primary Amnion Cell Senescence
Authors: Behnia Faranak , Peltier Morgan R. , Saade George R. , Menon Ramkumar
Published: July 2015

Objective

Polybrominated diphenyl ethers (PBDEs) are documented to increase the risk for spontaneous preterm birth (PTB). We hypothesize that PBDEs cause oxidative stress (OS) that leads to fetal cell senescence and inflammation associated with PTB.

Methods

Primary amnion epithelial cells (n = 5) isolated from term, not in labor pregnancies, were exposed to PBDE congeners 47 and 99 (each 5 μm). ROS kinetics was monitored. Morphologic changes, phospho‐p38 MAPK (P‐p38) activation, development of senescence, and induction of uterotonins (COX‐2 expression) were quantified using light microscopy, Western blot, senescence‐associated β‐galactosidase (SA β‐gal) staining, and qRT‐PCR, respectively, after 48 and 72 hr of exposure.

Results

Both PBDE congeners induced ROS within 2 min compared to controls (P < 0.05). P‐p38 activation was significant after PBDE‐99 treatment than controls (P < 0.05). After 72 hr of treatment, both PBDE‐treated cells showed cell death‐associated morphologic changes with significantly higher SA β‐gal‐stained cells than control. COX‐2 expression was higher after 72 hr of treatment with PBDE‐99. Overall, the PBDE‐99 response was more pronounced than PBDE‐47.

Conclusions

Congener‐dependent OS response, p38 MAPK activation, senescence, and COX‐2 expression were seen in human amnion cells by PBDEs. These findings demonstrate environment pollutant‐induced senescence activation and inflammation can lead to pathways resulting in PTB.
URB937, a peripherally restricted inhibitor for fatty acid amide hydrolase, reduces prostaglandin E2‐induced bladder overactivity and hyperactivity of bladder mechano‐afferent nerve fibres in rats
Authors: Aizawa Naoki , Gandaglia Giorgio , Hedlund Petter , Fujimura Tetsuya , Fukuhara Hiroshi , Montorsi Francesco , Homma Yukio , Igawa Yasuhiko
Published: July 2015

Objective

To determine if inhibition of the endocannabinoid‐degrading enzyme fatty acid amide hydrolase (FAAH) can counteract the changes in urodynamic variables and bladder afferent activities induced by intravesical prostaglandin E2 (PGE2) instillation in rats.

Materials and methods

In female Sprague–Dawley rats we studied the effects of URB937, a peripherally restricted FAAH inhibitor, on single‐unit afferent activity (SAA) during PGE2‐induced bladder overactivity (BO). SAA measurements were made in urethane‐anaesthetised rats and Aδ‐ and C‐fibres were identified by electrical stimulation of the pelvic nerve and by bladder distention. Cystometry (CMG) in conscious animals and during SAA measurements was performed during intravesical instillation of PGE2 (50 or 100 μm) after intravenous administration of URB937 (0.1 and 1 mg/kg) or vehicle. In separate experiments, the comparative expressions of FAAH and cannabinoid receptors, CB1 and CB2, in microsurgically removed L6 dorsal root ganglion (DRG) were studied by immunofluorescence.

Results

During CMG, 1 mg/kg URB937, but not vehicle or 0.1 mg/kg URB937, counteracted the PGE2‐induced changes in urodynamic variables. PGE2 increased the SAAs of C‐fibres, but not Aδ‐fibres. URB937 (1 mg/kg) depressed Aδ‐fibre SAA and abolished the facilitated C‐fibre SAA induced by PGE2. The DRG nerve cells showed strong staining for FAAH, CB1 and CB2, with a mean (sem) of 77 (2)% and 87 (3)% of FAAH‐positive nerve cell bodies co‐expressing CB1 or CB2 immunofluorescence, respectively.

Conclusion

The present results show that URB937, a peripherally restricted FAAH inhibitor, reduces BO and C‐fibre hyperactivity in the rat bladder provoked by PGE2, suggesting an important role of the peripheral endocannabinoid system in BO and hypersensitivity.
Prognostic value of Caveolin‐1 in patients treated with radical prostatectomy: a multicentric validation study
Authors: Mathieu Romain , Klatte Tobias , Lucca Ilaria , Mbeutcha Aurélie , Seitz Christian , Karakiewicz Pierre I. , Fajkovic Harun , Sun Maxine , Lotan Yair , Scherr Douglas S. , Montorsi Francesco , Briganti Alberto , Rouprêt Morgan , Margulis Vitaly , Rink Michael , Kluth Luis A. , Rieken Malte , Kenner Lukas , Susani Martin , Robinson Brian D. , Xylinas Evanguelos , Loidl Wolgang , Shariat Shahrokh F.
Published: July 2015

Objective

To validate Caveolin‐1 as an independent prognostic marker of biochemical recurrence (BCR) in a large multi‐institutional cohort of patients with prostate cancer treated with radical prostatectomy (RP).

Patients and Methods

Caveolin‐1 expression was evaluated by immunochemistry on a tissue microarray in 3 117 patients treated with RP for prostate cancer at five institutions. Univariable and multivariable Cox proportional hazards regression models assessed the association of Caveolin‐1 status with BCR. Harrell's c‐index quantified prognostic accuracy.

Results

Caveolin‐1 was overexpressed in 644 (20.6%) patients and was associated with higher pathological Gleason sum (P = 0.002) and lymph node metastases (P = 0.05). Within a median (interquartile range) follow‐up of 38 (21–66) months, 617 (19.8%) patients experienced BCR. Patients with overexpression of Caveolin‐1 had worse BCR‐free survival than those with normal expression (log‐rank test, P = 0.004). Caveolin‐1 was an independent predictor of BCR in multivariable analyses that adjusted for the effects of standard clinicopathological features (hazard ratio 1.21, P = 0.037). Addition of Caveolin‐1 in a model for prediction of BCR based on these standard prognosticators did not significantly improve the predictive accuracy of the model. In subgroup analyses, Caveolin‐1 was associated with BCR in patients with favourable pathological features (pT2pN0 and Gleason score = 6; P = 0.021).

Conclusions

We confirmed that overexpression of Caveolin‐1 is associated with adverse pathological features in prostate cancer and independently predicts BCR after RP, especially in patients with favourable pathological features. However, it did not add prognostically relevant information to established predictors of BCR, limiting its use in clinical practice.
Functional role of the transient receptor potential melastatin 8 (TRPM8) ion channel in the urinary bladder assessed by conscious cystometry and ex vivo measurements of single‐unit mechanosensitive bladder afferent activities in the rat
Authors: Ito Hiroki , Aizawa Naoki , Sugiyama Rino , Watanabe Shuzo , Takahashi Nobuyuki , Tajimi Masaomi , Fukuhara Hiroshi , Homma Yukio , Kubota Yoshinobu , Andersson Karl‐Erik , Igawa Yasuhiko
Published: July 2015

Objective

To evaluate the role of the transient receptor potential melastatin 8 (TRPM8) channel on bladder mechanosensory function by using L‐menthol, a TRPM8 agonist, and RQ‐00203078 (RQ), a selective TRPM8 antagonist.

Materials and methods

Female Sprague–Dawley rats were used. In conscious cystometry (CMG), the effects of intravesical instillation of L‐menthol (3 mm) were recorded after intravenous (i.v.) pretreatment with RQ (3 mg/kg) or vehicle. The direct effects of RQ on conscious CMG and deep body temperature were evaluated with cumulative i.v. administrations of RQ at 0.3, 1, and 3 mg/kg. Single‐unit mechanosensitive bladder afferent activities (SAAs) were monitored in a newly established ex vivo rat bladder model to avoid systemic influences of the drugs. Recordings were performed after cumulative intra‐aortic administration of RQ (0.3 and 3 mg/kg) with or without intra‐vesical L‐menthol instillation (3 mm).

Results

Intravesical L‐menthol decreased bladder capacity and voided volume, which was counteracted by RQ‐pretreatment. RQ itself increased bladder capacity and voided volume, and lowered deep body temperature in a dose‐dependent manner. RQ decreased mechanosensitive SAAs of C‐fibres, and inhibited the activation of SAAs induced by intravesical L‐menthol.

Conclusion

Our results suggest that TRPM8 channels have a role in activation of bladder afferent pathways during filling of the bladder in the normal rat. This effect seems, at least partly, to be mediated via mechanosensitive C‐fibres.
Proposed prognostic scoring system evaluating risk factors for biochemical recurrence of prostate cancer after salvage radiation therapy
Authors: Lee Richard J. , Tzou Katherine S. , Heckman Michael G. , Hobbs Corey J. , Rawal Bhupendra , Diehl Nancy N. , Peterson Jennifer L. , Paryani Nitesh N. , Ko Stephen J. , Daugherty Larry C. , Vallow Laura A. , Wong William , Schild Steven , Pisansky Thomas M. , Buskirk Steven J.
Published: July 2015

Objective

To update a previously proposed prognostic scoring system that predicts risk of biochemical recurrence (BCR) after salvage radiation therapy (SRT) for recurrent prostate cancer when using additional patients and a PSA value of 0.2 ng/mL and rising as the definition of BCR.

Patients and Methods

We included 577 patients who received SRT for a rising PSA after radical prostatectomy in this retrospective cohort study. Clinical, pathological, and SRT characteristics were evaluated for association with BCR using relative risks (RRs) from multivariable Cox regression models.

Results

With a median follow‐up of 5.5 years after SRT, 354 patients (61%) experienced BCR. At 5 years after SRT, 40% of patients were free of BCR. Independent associations with BCR were identified for the PSA level before SRT (RR [doubling]: 1.25, P < 0.001), pathological tumour stage (RR [T3a vs T2] 1.21, P = 0.19; RR [T3b/T4 vs T2] 2.09, P < 0.001; overall P < 0.001), Gleason score (RR [7 vs <7] 1.63, P < 0.001; RR [8–10 vs <7] 2.28, P < 0.001; overall P < 0.001), and surgical margin status (RR [positive vs negative] 0.71, P = 0.003). We combined these four variables to create a prognostic scoring system that predicted BCR risk with a c‐index of 0.66. Scores ranged from 0 to 7, and 5‐year freedom from BCR for different levels of the score was as follows: Score = 0–1: 66%, Score = 2: 46%, Score = 3: 28%, Score = 4: 19%, and Score = 5–7: 15%.

Conclusion

We developed a scoring system that provides an estimation of the risk of BCR after SRT. These findings will be useful for patients and physicians in decision making for radiation therapy in the salvage setting.
Detection of differential item functioning in Rasch models by boosting techniques
Authors: Schauberger Gunther , Tutz Gerhard
Published: July 2015

Methods for the identification of differential item functioning (DIF) in Rasch models are typically restricted to the case of two subgroups. A boosting algorithm is proposed that is able to handle the more general setting where DIF can be induced by several covariates at the same time. The covariates can be both continuous and (multi‐)categorical, and interactions between covariates can also be considered. The method works for a general parametric model for DIF in Rasch models. Since the boosting algorithm selects variables automatically, it is able to detect the items which induce DIF. It is demonstrated that boosting competes well with traditional methods in the case of subgroups. The method is illustrated by an extensive simulation study and an application to real data.
Sendai virus‐mediated expression of reprogramming factors promotes plasticity of human neuroblastoma cells
Authors: Islam S. M. Rafiqul , Suenaga Yusuke , Takatori Atsushi , Ueda Yasuji , Kaneko Yoshiki , Kawana Hidetada , Itami Makiko , Ohira Miki , Yokoi Sana , Nakagawara Akira
Published: July 2015

Neuroblastoma (NB) is the most common extracranial solid tumor that originates from multipotent neural crest cells. NB cell populations that express embryonic stem cell‐associated genes have been identified and shown to retain a multipotent phenotype. However, whether somatic reprogramming of NB cells can produce similar stem‐cell like populations is unknown. Here, we sought to reprogram NB cell lines using an integration‐free Sendai virus vector system. Of four NB cell lines examined, only SH‐IN cells formed induced pluripotent stem cell‐like colonies (SH‐IN 4F colonies) at approximately 6 weeks following transduction. These SH‐IN 4F colonies were alkaline phosphatase‐positive. Array comparative genomic hybridization analysis indicated identical genomic aberrations in the SH‐IN 4F cells as in the parental cells. SH‐IN 4F cells had the ability to differentiate into the three embryonic germ layers in vitro, but rather formed NBs in vivo. Furthermore, SH‐IN 4F cells exhibited resistance to cisplatin treatment and differentiated into endothelial‐like cells expressing CD31 in the presence of vascular endothelial growth factor. These results suggest that SH‐IN 4F cells are partially reprogrammed NB cells, and could be a suitable model for investigating the plasticity of aggressive tumors.
Persistence of Initial Misanalysis With No Referential Ambiguity
Authors: Nakamura Chie , Arai Manabu
Published: July 2015

Previous research reported that in processing structurally ambiguous sentences comprehenders often preserve an initial incorrect analysis even after adopting a correct analysis following structural disambiguation. One criticism is that the sentences tested in previous studies involved referential ambiguity and allowed comprehenders to make inferences about the initial interpretation using pragmatic information, suggesting the possibility that the initial analysis persisted due to comprehenders' pragmatic inference but not to their failure to perform complete reanalysis of the initial misanalysis. Our study investigated this by testing locally ambiguous relative clause sentences in Japanese, in which the initial misinterpretation contradicts the correct interpretation. Our study using a self‐paced reading technique demonstrated evidence for the persistence of the initial analysis with this structure. The results from an eye‐tracking study further suggested that the phenomenon directly reflected the amount of support given to the initial incorrect analysis prior to disambiguating information: The more supported the incorrect main clause analysis was, the more likely comprehenders were to preserve the analysis even after the analysis was falsified. Our results thus demonstrated that the preservation of the initial analysis occurs not due to referential ambiguities but to comprehenders' difficulty to fully revise the highly supported initial interpretation.
Neuro‐oscillatory mechanisms of intersensory selective attention and task switching in school‐aged children, adolescents and young adults
Authors: Murphy Jeremy W. , Foxe John J. , Molholm Sophie
Published: July 2015

The ability to attend to one among multiple sources of information is central to everyday functioning. Just as central is the ability to switch attention among competing inputs as the task at hand changes. Such processes develop surprisingly slowly, such that even into adolescence, we remain slower and more error prone at switching among tasks compared to young adults. The amplitude of oscillations in the alpha band (~8–14 Hz) tracks the top‐down deployment of attention, and there is growing evidence that alpha can act as a suppressive mechanism to bias attention away from distracting sensory input. Moreover, the amplitude of alpha has also been shown to be sensitive to the demands of switching tasks. To understand the neural basis of protracted development of these executive functions, we recorded high‐density electrophysiology from school‐aged children (8–12 years), adolescents (13–17), and young adults (18–34) as they performed a cued inter‐sensory selective attention task. The youngest participants showed increased susceptibility to distracting inputs that was especially evident when switching tasks. Concordantly, they showed weaker and delayed onset of alpha modulation compared to the older groups. Thus the flexible and efficient deployment of alpha to bias competition among attentional sets remains underdeveloped in school‐aged children.
Risky visuomotor choices during rapid reaching in childhood
Authors: Dekker Tessa M. , Nardini Marko
Published: July 2015

Many everyday actions are implicit gambles because imprecisions in our visuomotor systems place probabilities on our success or failure. Choosing optimal action strategies involves weighting the costs and gains of potential outcomes by their corresponding probabilities, and requires stable representations of one's own imprecisions. How this ability is acquired during development in childhood when visuomotor skills change drastically is unknown. In a rewarded rapid reaching task, 6‐ to 11‐year‐old children followed ‘risk‐seeking’ strategies leading to overly high point‐loss. Adults' performance, in contrast, was close to optimal. Children's errors were not explained by distorted estimates of value or probability, but may reflect different action selection criteria or immature integration of value and probability information while planning movements. These findings provide a starting point for understanding children's risk‐taking in everyday visuomotor situations when suboptimal choices can be dangerous. Moreover, children's risky visuomotor decisions mirror those reported for non‐motor gambles, raising the possibility that common processes underlie development across decision‐making domains.
On the edge of language acquisition: inherent constraints on encoding multisyllabic sequences in the neonate brain
Authors: Ferry Alissa L. , Fló Ana , Brusini Perrine , Cattarossi Luigi , Macagno Francesco , Nespor Marina , Mehler Jacques
Published: July 2015

To understand language, humans must encode information from rapid, sequential streams of syllables – tracking their order and organizing them into words, phrases, and sentences. We used Near‐Infrared Spectroscopy (NIRS) to determine whether human neonates are born with the capacity to track the positions of syllables in multisyllabic sequences. After familiarization with a six‐syllable sequence, the neonate brain responded to the change (as shown by an increase in oxy‐hemoglobin) when the two edge syllables switched positions but not when two middle syllables switched positions (Experiment 1), indicating that they encoded the syllables at the edges of sequences better than those in the middle. Moreover, when a 25 ms pause was inserted between the middle syllables as a segmentation cue, neonates’ brains were sensitive to the change (Experiment 2), indicating that subtle cues in speech can signal a boundary, with enhanced encoding of the syllables located at the edges of that boundary. These findings suggest that neonates’ brains can encode information from multisyllabic sequences and that this encoding is constrained. Moreover, subtle segmentation cues in a sequence of syllables provide a mechanism with which to accurately encode positional information from longer sequences. Tracking the order of syllables is necessary to understand language and our results suggest that the foundations for this encoding are present at birth.
Family Firms, Corporate Governance and Export
Authors: Minetti Raoul , Murro Pierluigi , Zhu Susan Chun
Published: July 2015

This paper investigates the effects of family ownership on export using rich data on Italian firms. We find that family ownership increases the probability that firms export. This benefit is especially pronounced when family owners retain control rights and seek the support of external managers. The results suggest that families better internalize the long‐run benefits of internationalization, but that their limited competencies attenuate this benefit in high‐tech industries and in remote and unfamiliar export markets. Family firms also exhibit some tendency to enter foreign markets in a progressive way (sequential exporting) and through limited collaborations with foreign firms and intermediaries.
Gum acacia mitigates genetic damage in adenine‐induced chronic renal failure in rats
Authors: Ali B.H. , Al Balushi K. , Al‐Husseini I. , Mandel P. , Nemmar A. , Schupp N. , Ribeiro D.A.
Published: July 2015

Background

Subjects with chronic renal failure (CRF) exhibit oxidative genome damage, which may predispose to carcinogenesis, and Gum acacia (GumA) ameliorates this condition in humans and animals. We evaluated here renal DNA damage and urinary excretion of four nucleic acid oxidation adducts namely 8‐oxoguanine (8‐oxoGua), 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine (8‐oxodG), 8‐oxoguanosine (8‐oxoGuo) and 8‐hydroxy‐2‐deoxyguanisone (8‐OHdg) in rats with adenine (ADE)‐induced CRF with and without GumA treatment.

Materials and Methods

Twenty‐four rats were divided into four equal groups and treated for 4 weeks. The first group was given normal food and water (control). The second group was given normal food and GumA (15% w/v) in drinking water. The third group was fed powder diet containing adenine (ADE) (0·75% w/w in feed). The fourth group was fed like in the third group, plus GumA in drinking water (15%, w/v).

Results

ADE feeding induced CRF (as measured by several physiological, biochemical and histological indices) and also caused a significant genetic damage and significant decreases in urinary 8‐oxo Gua and 8‐oxoGuo, but not in the other nucleic acids. However, concomitant GumA treatment reduced the level of genetic damage in kidney cells as detected by Comet assay and significantly reversed the effect of adenine on urinary 8‐oxoGuo.

Conclusions

Treatment with GumA is able to mitigate genetic damage in renal tissues of rats with ADE‐induced CRF.
Clinical features and survival of 338 multiple myeloma patients treated with hematopoietic stem cell transplantation or conventional chemotherapy
Authors: Pérez Raúl , Durán Mª Sol , Mayans Jose , Soler Alfons , Castillo Inmaculada , Jurado Manuel , Ribas Paz , Menchaca Echevarria Mª Carmen , Hernandez Miguel T. , Lopez Garcia‐Carreño Mª Dolores , Echeveste Gutierrez Asunción , Bailen Garcia Alicia , Lopez Silvia , Baquero Jose , Ramirez Gemma
Published: July 2015

Therapeutic approaches against multiple myeloma (MM) have largely changed during the past decade. Hematopoietic stem cell transplantation (HSCT) and licensing of immunomodulators and proteasome inhibitors have resulted in better response and increased overall survival rates compared to previous conventional therapies. To assess the impact that these new strategies have had on outcome of patients with symptomatic MM in Spain, we conducted an epidemiological retrospective analysis of 338 newly diagnosed patients with stage II‐III MM who started first‐line treatment over a 2‐yr period (2003–2005) by collecting data from their medical records. Most patients had been diagnosed with secretory MM (94.4%), 41.7% stage II and 58.3% stage III. The presence of bone lesions (72.2%), as well as anemia (79.8%) and elevated beta2‐microglobulin levels (62.3%), was a common finding; in contrast, hypercalcemia and elevated serum creatinine were less frequent (25% each). First‐line treatment had consisted of either conventional chemotherapy (62%) or induction treatment plus autologous HSCT (38%), as per standard clinical practice. HSCT not only resulted in greater objective response rates (93% vs. 50%), but also contributed to a significant increase in 3‐yr survival (85% vs. 49.7%; 95% CI, range 77–91 vs. 41–58; P < 0.001). Overall, 55% of patients presented treatment‐related adverse events, mainly hematological. Toxicity rates were higher among patients treated with alkylating‐based regimens and in those undergoing transplantation. In conclusion, data analysis shows an adequate balance between increased response rates and safety that supports the use of up‐front high‐dose HSCT therapy in younger patients. Most importantly, this study provides further confirmation that the introduction of HSCT has significantly prolonged survival of patients with MM.
Strategies to enable equitable delivery of acute endovascular treatment to stroke patients
Authors: Yan B.
Published: July 2015

Click here to view the accompanying paper in this issue.
The Trojan Female Technique for pest control: a candidate mitochondrial mutation confers low male fertility across diverse nuclear backgrounds in Drosophila melanogaster
Authors: Dowling Damian K. , Tompkins Daniel M. , Gemmell Neil J.
Published: July 2015

Pest species represent a major ongoing threat to global biodiversity. Effective management approaches are required that regulate pest numbers, while minimizing collateral damage to nontarget species. The Trojan Female Technique (TFT) was recently proposed as a prospective approach to biological pest control. The TFT draws on the evolutionary hypothesis that maternally inherited mitochondrial genomes are prone to the accumulation of male, but not female, harming mutations. These mutations could be harnessed to provide trans‐generational fertility‐based control of pest species. A candidate TFT mutation was recently described in the fruit fly, Drosophila melanogaster, which confers male‐only sterility in the specific isogenic nuclear background in which it is maintained. However, applicability of the TFT relies on mitochondrial mutations whose male‐sterilizing effects are general across nuclear genomic contexts. We test this assumption, expressing the candidate TFT‐mutation bearing haplotype alongside a range of nuclear backgrounds and comparing its fertility in males, relative to that of control haplotypes. We document consistently lower fertility for males harbouring the TFT mutation, in both competitive and noncompetitive mating contexts, across all nuclear backgrounds screened. This indicates that TFT mutations conferring reduced male fertility can segregate within populations and could be harnessed to facilitate this novel form of pest control.
Chronic hepatitis without hepatic steatosis caused by citrin deficiency in a child
Authors: Inui Ayano , Hashimoto Takuji , Sogo Tsuyoshi , Komatsu Haruki , Saheki Takeyori , Fujisawa Tomoo
Published: July 2015

Citrin deficiency manifests as both neonatal intrahepatic cholestasis (NICCD) during early infancy and adult‐onset type II citrullinemia during adulthood. Hepatic steatosis is most frequently observed in patients with citrin deficiency. Thus, non‐alcoholic fatty liver disease that is unrelated to being overweight is considered one of the clinical features of citrin deficiency in children and adults. However, it remains unknown whether citrin deficiency is a cause of chronic hepatitis in the absence of fatty changes to the liver that occur during childhood. We encountered an 8‐year‐old girl who showed no clinical features of NICCD during infancy and had persistently elevated transaminase levels for several years. Liver biopsy showed widening of the portal tracts with intense mononuclear cell infiltration and mild fibrosis but no fatty changes. However, she had peculiar dietary habits similar to those that have been observed in many patients with citrin deficiency. In addition, a slightly elevated plasma citrulline level and a high pancreatic secretory trypsin inhibitor level were detected by blood examination, and she was diagnosed with citrin deficiency. Analysis of the SLC25A13 gene revealed the presence of the compound heterozygous mutations 851del4 and IVS13 + 1G > A. Thus, citrin deficiency should be included in the differential diagnosis of chronic hepatitis in children, even in the absence of hepatic steatosis.
Facile Synthesis of Element‐Substituted Hydroxyapatite Whiskers Using α‐Tricalcium Phosphate as Precursors
Authors: Yin Zhilan , Wang Xiaoya , Wang Xiuhui , Zhang Na , Chen Lei , Qu Haiyun , Chang Jiang , Ren Zhongming , Lin Kaili
Published: July 2015

In the absence of any surfactants, organic solvents or structure‐directing reagents, the cation‐ and anion‐substituted HAp whiskers, and cation‐/anion‐co‐substituted HAp whiskers with controllable substitution amounts were successfully synthesized via hydrothermal treatment of the same precursor of α‐TCP in an aqueous solution containing the objective substituted elements. Through regulating the initial ion concentrations of the aqueous solutions, the element substitution level could be well facilely tailored. The cytocompatibility of the products was confirmed by Cell Counting Kit‐8 (CCK‐8) assay using the osteoblast cell line MC3T3‐E1. This study provided a facile strategy for the synthesis of element‐substituted HAp materials.
The Importance of the Chief Audit Executive's Communication: Experimental Evidence on Internal Auditors' Judgments in a ‘Two Masters Setting’
Authors: Hoos Florian , Kochetova‐Kozloski Natalia , d'Arcy Anne Christine
Published: July 2015

The position of an internal audit function (IAF) as a ‘servant of two masters’ (i.e., management and the audit committee) may lead to a conflict of priorities. In this setting, the tone at the top set by the Chief Audit Executive (CAE) plays a critical role in balancing the potentially competing priorities of the ‘two masters’. We test two hypotheses in a mixed experimental design with the communicated preferences of the CAE to subordinates (cost reduction vs. effectiveness of internal controls) as a between‐subjects factor, and levels of ambiguity (low, medium, high) manipulated within‐subjects. Findings suggest that the emphasis in the CAE's message can influence internal auditors' judgments, and such influence is more pronounced when task ambiguity is high, resulting in the elimination of a significantly greater number of internal controls and the design of less effective processes. We discuss implications of our results for modern IAFs and the role of the CAE.
Consumption, lifestyle and social movements
Authors: Wahlen Stefan , Laamanen Mikko
Published: July 2015

In this editorial, we contemplate how the politics of the everyday in consumption and consumer lifestyles emerge. Foundational here is the overarching question why, how and where do people come to share common spaces, meaning, identity, practice and goals in dispersed lifestyles aiming for (social) change. This special issue is an original endeavour to generate an understanding of the issues, problems and potential for change emerging from individual and collective efforts in and around consumption and lifestyles. The editorial presents principles and commonalities of the intersectional study of consumption, lifestyle and social movements. We connect these principles with the papers that make up the special issue and conclude with an outlook for future research.
Genetic signatures of historical dispersal of fish threatened by biological invasions: the case of galaxiids in South America
Authors: Vanhaecke Delphine , Garcia de Leaniz Carlos , Gajardo Gonzalo , Dunham Jason , Giannico Guillermo , Consuegra Sofia
Published: July 2015

Aim

The ecological effects of biological invasions are well documented, but little is known about the effects of invaders on the genetic structure of native species. We examined the phylogeography, genetic variation and population structuring of two galaxiid fishes, Aplochiton zebra and A. taeniatus, threatened by non‐native salmonids, and whose conservation is complicated by misidentification and limited knowledge of their genetic diversity.

Location

Chile and the Falkland Islands.

Methods

We combined microsatellite and mitochondrial DNA (16S rDNA and COI) markers to compare genetic diversity, effective population size and gene flow of Aplochiton spp. populations differentially affected by salmonid presence.

Results

We identified two 16S rDNA haplotypes among A. zebra – one dominant in coastal populations and another dominant in inland populations. Populations living on the island of Chiloé displayed a mixture of coastal and inland haplotypes, as well as high microsatellite diversity, as one would expect if the island had been a refugium during the Last Glacial Maximum, or a contact zone among populations. Microsatellite data revealed strong population structuring, indicative of current isolation patterns, and a negative correlation between the genetic diversity of A. zebra and the relative abundance of invasive salmonids.

Main conclusions

Our study indicates that population structuring of A. zebra reflects the influence of historical patterns of migration, but also the current levels of reduced gene flow among watersheds. Invasive salmonids, known to compete with and prey on native galaxiids, may have had negative impacts on the genetic diversity of Aplochiton spp. The low genetic variation found in some populations, coupled with potential biases in abundance estimates due to species misidentification, highlight the urgent need for more research into the conservation status of the two species of Aplochiton.