bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term consequences of neonatal fluoxetine exposure in adult rats
Authors: Ko Meng‐Ching , Lee Lukas Jyuhn‐Hsiarn , Li Yang , Lee Li‐Jen
Published: April 2014

Serotonin (5‐HT) plays important roles during neural development. Administration of selective serotonin reuptake inhibitor (SSRI)‐type medication during gestation may influence the maturation of the fetal brain and subsequent brain functions. To mimic the condition of late‐gestation SSRI exposure, we administered fluoxetine (FLX) in neonatal rats during the first postnatal week, which roughly corresponds to the third trimester period of human gestation. FLX‐exposed adult male rats exhibited reduced locomotor activity and depression‐like behaviors. Furthermore, sensorimotor gating capacity was also impaired. Interestingly, increased social interaction was noticed in FLX‐exposed rats. When the levels of 5‐HT and tryptophan hydroxylase were examined, no significant changes were found in FLX rats compared to control (CON) rats. The behavioral phenotypes of FLX rats suggested malfunction of the limbic system. Dendritic architectures of neurons in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) were examined. Layer II/III mPFC pyramidal neurons in FLX rats had exuberant dendritic branches with elongated terminal segments compared to those in CON rats. In BLA pyramidal neurons, the dendritic profiles were comparable between the two groups. However, in FLX rats, the density of dendritic spines was reduced in both mPFC and BLA. Together, our results demonstrated the long‐lasting effects of early FLX treatment on emotional and social behaviors in adult rats in which impaired neuronal structure in the limbic system was also noticed. The risk of taking SSRI‐type antidepressants during pregnancy should be considered. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 1038–1051, 2014
Rostral–caudal distribution of Emx1‐lineage stem/transit amplifying cells and lineage progression in embryonic cortex depend on hedgehog signaling
Authors: Lillien Laura
Published: April 2014

Lineage progression of neural precursors to an EGF‐responsive state can be promoted by several extrinsic signals, including fibroblast growth factor 2 (FGF2) and Hedgehog (Hh). It has been suggested that EGF‐responsive precursors in the embryonic cerebral cortex originate in the ventral telencephalon in an FGF‐dependent manner and migrate dorsally. To determine whether cortical EGF‐responsive cells originate locally from dorsal precursors, we marked these precursors using Emx1‐cre and the cre reporter Z/EG and observed a local origin for EGF‐responsive cells. We also found a rostral–caudal difference in the abundance of self‐renewing, neurogenic Emx1‐lineage precursors, with more present rostrally. Deleting the Hh receptor smoothened in Emx‐1 lineage cells impaired their progression to an EGF‐responsive state. Moreover, loss of smoothened increased the proportion of neurogenic, self‐renewing Emx1‐lineage cells in caudal regions of cortex, eliminating their asymmetric distribution. Our results support the idea that Hh signaling promotes lineage progression of stem/transit amplifying cells, particularly in caudal regions of the embryonic cortex, leading to rostral–caudal differences in the abundance of neurogenic, self‐renewing precursors.© 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 1096–1109, 2014
Transcriptome of Atoh7 retinal progenitor cells identifies new Atoh7‐dependent regulatory genes for retinal ganglion cell formation
Authors: Gao Zhiguang , Mao Chai‐An , Pan Ping , Mu Xiuqian , Klein William H.
Published: May 2014

The bHLH transcription factor ATOH7 (Math5) is essential for establishing retinal ganglion cell (RGC) fate. However, Atoh7‐expressing retinal progenitor cells (RPCs) can give rise to all retinal cell types, suggesting that other factors are involved in specifying RGCs. The basis by which a subpopulation of Atoh7‐expressing RPCs commits to an RGC fate remains uncertain but is of critical importance to retinal development since RGCs are the earliest cell type to differentiate. To better understand the regulatory mechanisms leading to cell‐fate specification, a binary genetic system was generated to specifically label Atoh7‐expressing cells with green fluorescent protein (GFP). Fluorescence‐activated cell sorting (FACS)‐purified GFP+ and GFP− cells were profiled by RNA‐seq. Here, we identify 1497 transcripts that were differentially expressed between the two RPC populations. Pathway analysis revealed diminished growth factor signaling in Atoh7‐expressing RPCs, indicating that these cells had exited the cell cycle. In contrast, axon guidance signals were enriched, suggesting that axons of Atoh7‐expressing RPCs were already making synaptic connections. Notably, many genes enriched in Atoh7‐expressing RPCs encoded transcriptional regulators, and several were direct targets of ATOH7, including, and unexpectedly, Ebf3 and Eya2. We present evidence for a Pax6‐Atoh7‐Eya2 pathway that acts downstream of Atoh7 but upstream of differentiation factor Pou4f2. EYA2 is a protein phosphatase involved in protein–protein interactions and posttranslational regulation. These properties, along with Eya2 as an early target gene of ATOH7, suggest that EYA2 functions in RGC specification. Our results expand current knowledge of the regulatory networks operating in Atoh7‐expressing RPCs and offer new directions for exploring the earliest aspects of retinogenesis. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 1123–1140, 2014
A population of progenitor cells in the basal and intermediate layers of the murine bladder urothelium contributes to urothelial development and regeneration
Authors: Colopy Sara A. , Bjorling Dale E. , Mulligan William A. , Bushman Wade
Published: May 2014

Background: Homeostatic maintenance and repair of the bladder urothelium has been attributed to proliferation of keratin 5‐expressing basal cells (K5‐BC) with subsequent differentiation into superficial cells. Recent evidence, however, suggests that the intermediate cell layer harbors a population of progenitor cells. We use label‐retaining cell (LRC) methodology in conjunction with a clinically relevant model of uropathogenic Escherichia coli (UPEC)‐induced injury to characterize urothelial ontogeny during development and in response to diffuse urothelial injury. Results: In the developing urothelium, proliferating cells were dispersed throughout the K5‐BC and intermediate cells layers, becoming progressively concentrated in the K5‐BC layer with age. When 5‐bromo‐2‐deoxyuridine (BrdU) was administered during urothelial development, LRCs in the adult were found within the K5‐BC, intermediate, and superficial cell layers, the location dependent upon time of labeling. UPEC inoculation resulted in loss of the superficial cell layer followed by robust proliferation of K5‐BCs and intermediate cells. LRCs within the K5‐BC and intermediate cell layers proliferated in response to injury. Conclusions: Urothelial development and regeneration following injury relies on proliferation of K5‐BC and intermediate cells. The existence and proliferation of LRCs within both the K5‐BC and intermediate cell layers suggests the presence of two populations of urothelial progenitor cells. Developmental Dynamics 243::988–998, 2014. © 2014 Wiley Periodicals, Inc.
Generation of a Magoh conditional allele in mice
Authors: McMahon John J. , Shi Lei , Silver Debra L.
Published: April 2014

Magoh encodes a core component of the exon junction complex (EJC), which binds mRNA and regulates mRNA metabolism. Magoh is highly expressed in proliferative tissues during development. EJC components have been implicated in several developmental disorders including TAR syndrome, Richieri–Costa–Pereira syndrome, and intellectual disability. Existing germline null Magoh mice are embryonic lethal as homozygotes and perinatal lethal as heterozygotes, precluding detailed analysis of embryonic and postnatal functions. Here, we report the generation of a new genetic tool to dissect temporal and tissue‐specific roles for Magoh in development and adult homeostasis. This Magoh conditional allele has two loxP sites flanking the second exon. Ubiquitous Cre‐mediated deletion of the floxed allele in a heterozygous mouse (Magohdel/+) causes 50% reduction of both Magoh mRNA and protein. Magohdel/+ mice exhibit both microcephaly and hypopigmentation, thus phenocopying germline haploinsufficient Magoh mice. Using Emx1‐Cre, we further show that conditional Magoh deletion in neural progenitors during embryonic development also causes microcephaly. We anticipate this novel conditional allele will be a valuable tool for assessing tissue‐specific roles for Magoh in mammalian development and postnatal processes. genesis 52:752–758, 2014. © 2014 Wiley Periodicals, Inc.
Normative data for female adolescents with eating disorders on the Children's depression inventory
Authors: Watson Hunna J. , Egan Sarah J. , Limburg Karina , Hoiles Kimberley J.
Published: May 2014

Objective

Given the importance of assessing depressive symptoms and suicidal ideation in adolescents with eating disorders (EDs), the aim was to provide normative data on the Children's Depression Inventory (CDI) for female adolescents presenting for treatment of an ED.

Method

The data source was the Helping to Outline Paediatric Eating Disorders (HOPE) Project registry (N = 1000), a prospective, ongoing registry study comprising consecutive pediatric tertiary ED referrals. Females (N = 256; 12–17 years) with DSM‐5 EDs completed the CDI at intake.

Results

Results on the CDI revealed a pattern of increasing depressive scores with age and higher scores among patients with anorexic spectrum disorders. The prevalence of suicidal ideation was high and had the same pattern as CDI scores. The mean score on the CDI in the sample was higher than community samples and clinical samples of adolescents with post‐traumatic stress disorder, obsessive compulsive disorder, and other clinical disorders.

Discussion

Females adolescents with EDs are at high‐risk of depression and suicidal ideation. These data provide information about variation in CDI scores to guide clinicians in interpretation of scores. © 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:666–670)
Differences in evolutionary history translate into differences in invasion success of alien mammals in South Africa
Authors: Yessoufou Kowiyou , Gere Jephris , Daru Barnabas H. , van der Bank Michelle
Published: April 2014

Attempts to investigate the drivers of invasion success are generally limited to the biological and evolutionary traits distinguishing native from introduced species. Although alien species introduced to the same recipient environment differ in their invasion intensity – for example, some are “strong invaders”; others are “weak invaders” – the factors underlying the variation in invasion success within alien communities are little explored. In this study, we ask what drives the variation in invasion success of alien mammals in South Africa. First, we tested for taxonomic and phylogenetic signal in invasion intensity. Second, we reconstructed predictive models of the variation in invasion intensity among alien mammals using the generalized linear mixed‐effects models. We found that the family Bovidae and the order Artiodactyla contained more “strong invaders” than expected by chance, and that such taxonomic signal did not translate into phylogenetic selectivity. In addition, our study indicates that latitude, gestation length, social group size, and human population density are only marginal determinant of the variation in invasion success. However, we found that evolutionary distinctiveness – a parameter characterising the uniqueness of each alien species – is the most important predictive variable. Our results indicate that the invasive behavior of alien mammals may have been “fingerprinted” in their evolutionary past, and that evolutionary history might capture beyond ecological, biological and life‐history traits usually prioritized in predictive modeling of invasion success. These findings have applicability to the management of alien mammals in South Africa.
Tandem Nucleophilic Addition/Oxa‐Michael Reaction for the Synthesis of cis‐2,6‐Disubstituted Tetrahydropyrans
Authors: Gharpure Santosh J. , Prasad J. V. K. , Bera Kalisankar
Published: April 2014

A Lewis acid catalyzed tandem nucleophilic addition/oxa‐Michael reaction was developed for the synthesis of cis‐2,6‐disubstituted tetrahydropyran (THP) derivatives in good yields with excellent diastereoselectivities. The strategy was successfully used in the construction of THP derivatives with three stereocenters in a highly stereoselective fashion.
A 2D reconstruction for the transverse coupling of shallow water models
Authors: Goutal Nicole , Parisot Martin , Zaoui Fabrice
Published: May 2014

This work is dedicated to the modeling of exchanges between a river and its surrounding floodplains during floods overflowing its bed. Modeling flows in each subdomain, that of the river and that of the floodplain, has been the subject of numerous works for over 50 years and is now well understood. A coupling strategy is considered in order to preserve the advantages of 1D and 2D models in their respective subdomains. In comparison with other transverse coupling strategies already presented in the literature, we introduce a direct method, without overlapping the models or introducing numerical parameters. This strategy is based on the resolution of the Riemann 2D problem at the coupling interface (the bank) and requires the estimation of the transverse velocity close to the interface. We propose a model of transverse velocity using successive resolutions of Riemann problems. Then, we present a numerical resolution of the coupling system, based on a finite volume method for any Riemann solvers. Particular attention was given to the essential properties of the model (conservation of mass, positivity of water depth, and well‐balanced scheme). Lastly, the precision and efficiency of the method are illustrated using examples of simulations. Copyright © 2014 John Wiley & Sons, Ltd.
Initial investigation of dietitian perception of plant‐based protein quality
Authors: Hughes Glenna J. , Kress Kathleen S. , Armbrecht Eric S. , Mukherjea Ratna , Mattfeldt‐Beman Mildred
Published: April 2014

Interest in plant‐based diets is increasing, evidenced by scientific and regulatory recommendations, including Dietary Guidelines for Americans. Dietitians provide guidance in dietary protein selection but little is known about how familiar dietitians are with the quality of plant versus animal proteins or methods for measuring protein quality. Likewise, there is a need to explore their beliefs related to dietary recommendations. The aim of this study was to assess dietitians' perceptions of plant‐based protein quality and to determine if these are affected by demographic factors such as age and dietary practice group (DPG) membership. This was a cross‐sectional design using an online survey. The survey was sent to all members of the Missouri Dietetic Association. All completed surveys (136) were analyzed. The main outcome measures were responses to belief and knowledge questions about the protein quality of plant‐based diets, along with demographic information including age and DPG membership. Descriptive statistics and frequencies were determined, and chi‐square analysis was used to determine the associations between belief and knowledge responses and demographic characteristics. Responses to belief statements suggested a high level of support for plant‐based diets. No associations were found between any of the belief questions and demographic factors. A majority of respondents were not familiar with protein quality determination methods that are currently recognized by global regulatory and advisory agencies. Potential barriers identified in shifting to a more plant‐based diet were lack of interest and perceived difficulty. Knowledge among dietitians of plant‐based protein quality in general, and methods of protein quality measurement more specifically, needs to be addressed to enhance their knowledge base for making dietary protein recommendations. Two potential avenues for training are university curricula and continuing education opportunities provided to practitioners who provide dietary advice.
Incorporation of primary patient-derived glycoproteins into authentic infectious hepatitis C virus particles
Authors: Doerrbecker Juliane , Friesland Martina , Riebesehl Nina , Ginkel Corinne , Behrendt Patrick , Brown Richard J.P. , Ciesek Sandra , Wedemeyer Heiner , Sarrazin Christoph , Kaderali Lars , Pietschmann Thomas , Steinmann Eike
Published: April 2014

The Japanese fulminant hepatitis-1 (JFH1)-based hepatitis C virus (HCV) infection system has permitted analysis of the complete viral replication cycle in vitro. However, lack of robust infection systems for primary, patient-derived isolates limits systematic functional studies of viral intrahost variation and vaccine development. Therefore, we aimed at developing cell culture models for incorporation of primary patient-derived glycoproteins into infectious HCV particles for in-depth mechanistic studies of envelope gene function. To this end, we first constructed a packaging cell line expressing core, p7, and NS2 based on the highly infectious Jc1 genotype (GT) 2a chimeric genome. We show that this packaging cell line can be transfected with HCV replicons encoding cognate Jc1-derived glycoprotein genes for production of single-round infectious particles by way of trans-complementation. Testing replicons expressing representative envelope protein genes from all major HCV genotypes, we observed that virus production occurred in a genotype- and isolate-dependent fashion. Importantly, primary GT 2 patient-derived glycoproteins were efficiently incorporated into infectious particles. Moreover, replacement of J6 (GT 2a) core, p7, and NS2 with GT 1a-derived H77 proteins allowed production of infectious HCV particles with GT 1 patient-derived glycoproteins. Notably, adaptive mutations known to enhance virus production from GT 1a-2a chimeric genomes further increased virus release. Finally, virus particles with primary patient-derived E1-E2 proteins possessed biophysical properties comparable to Jc1 HCVcc particles, used CD81 for cell entry, were associated with ApoE and could be neutralized by immune sera. Conclusion: This work describes cell culture systems for production of infectious HCV particles with primary envelope protein genes from GT 1 and GT 2-infected patients, thus opening up new opportunities to dissect envelope gene function in an individualized fashion. (Hepatology 2014;60:508–520)
VEGF promotes osteogenic differentiation of ASCs on ordered fluorapatite surfaces
Authors: Clark D. , Wang X. , Chang S. , Czajka‐Jakubowska A. , Clarkson B. H. , Liu J.
Published: May 2014

Vascular endothelial growth factor (VEGF) has been reported to mediate both osteogenesis and angiogenesis in bone regeneration. We previously found an upregulation of VEGF in adipose‐derived stem cells (ASCs) when obvious mineralization occurred on a novel fluorapatite (FA)‐coated surfaces. This study investigated the effect of FA and VEGF on the growth, differentiation and mineralization of (ASC) grown on ordered FA surfaces. Cells grown on FA and treated with VEGF demonstrated osteogenic differentiation as measured with ALP staining, and obvious mineralization as measured by Alizarin red staining. A combined stimulating effect of FA and VEGF was seen using both indicators. VEGF signaling pathway perturbation using a specific VEGF receptor inhibitor showed the lowest levels of ALP and Alizarin red staining, which was partially rescued when the cells were grown on FA and/or treated with the addition of VEGF. The osteogenic differentiation of ASCs stimulated by these FA surfaces as well as VEGF has been shown to be mediated through, but probably not only, the VEGF signaling pathway. The enhancement of osteogenic differentiation and mineralization supports the potential use of therapeutic VEGF and FA coatings in bone regeneration. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 639–645, 2015.
Cell proliferation dynamics in regeneration of the operculum head appendage in the annelid Pomatoceros lamarckii
Authors: Szabó Réka , Ferrier David Ellard Keith
Published: May 2014

Regeneration of lost or damaged appendages is a widespread and ecologically important ability in the animal kingdom, and also of great significance to developing regenerative medicine. The operculum of serpulid polychaetes is one among the many diverse appendages found in the lophotrochozoan superphylum, a clade hitherto understudied with respect to the mechanisms of appendage regeneration. In this study, we establish the normal time course of opercular regeneration in the serpulid Pomatoceros lamarckii and describe cell proliferation patterns in the regenerating opercular filament. The P. lamarckii operculum regenerates through a rapid and consistent series of morphogenetic events. Based on 5‐bromo‐2′‐deoxyuridine (BrdU) labeling and anti‐phosphohistone H3 immunohistochemistry, opercular regeneration appears to be a mixture of an early morphallactic stage, and a later phase characterized by widespread proliferative activity within the opercular filament. Tracking residual pigmentation suggests that the distal part of the stump gives rise to the most distal structures of the operculum via morphallactic remodeling, whereas more proximal structures are derived from the proximal stump. Our work underscores the diversity of regenerative strategies employed by animals and introduces P. lamarckii as an emerging model of appendage regeneration. J. Exp. Zool. (Mol. Dev. Evol.) 322B: 257–268, 2014. © 2014 Wiley Periodicals, Inc.
Live cell imaging reveals differential modifications to cytoplasmic dynein properties by phospho‐ and dephosphomimic mutations of the intermediate chain 2C S84
Authors: Blasier Kiev R. , Humsi Michael K. , Ha Junghoon , Ross Mitchell W. , Smiley W. Russell , Inamdar Nirja A. , Mitchell David J. , Lo Kevin W.‐H. , Pfister K. Kevin
Published: May 2014

Cytoplasmic dynein is a multisubunit motor protein responsible for intracellular cargo transport toward microtubule minus ends. There are multiple isoforms of the dynein intermediate chain (DYNC1I, IC), which is encoded by two genes. One way to regulate cytoplasmic dynein is by IC phosphorylation. The IC‐2C isoform is expressed in all cells, and the functional significance of phosphorylation on IC‐2C serine 84 was investigated by using live cell imaging of fluorescent protein‐tagged IC‐2C wild type (WT) and phospho‐ and dephosphomimic mutant isoforms in axonal transport model systems. Both mutations modulated dynein functional properties. The dephosphomimic mutant IC‐2C S84A had greater colocalization with mitochondria than the IC‐2C WT or the phosphomimic mutant IC‐2C S84D. The dephosphomimic mutant IC‐2C S84A was also more likely to be motile than the phosphomimic mutant IC‐2C S84D or the IC‐2C WT. In contrast, the phosphomimic mutant IC‐2C S84D mutant was more likely to move in the retrograde direction than was the IC‐2C S84A mutant. The phosphomimic IC‐2C S84D was also as likely as the IC‐2C WT to colocalize with mitochondria. Both the S84D phospho‐ and the S84A dephosphomimic mutants were found to be capable of microtubule minus‐end‐directed (retrograde) movement in axons. They were also observed to be passively transported in the anterograde direction. These data suggest that the IC‐2C S84 has a role in modulating dynein properties. © 2014 Wiley Periodicals, Inc.
Distinct effect of impact rise times on immediate and early neuropathology after brain injury in juvenile rats
Authors: Neuberger Eric J. , Abdul Wahab Radia , Jayakumar Archana , Pfister Bryan J. , Santhakumar Vijayalakshmi
Published: May 2014

Traumatic brain injury (TBI) can occur from physical trauma from a wide spectrum of insults ranging from explosions to falls. The biomechanics of the trauma can vary in key features, including the rate and magnitude of the insult. Although the effect of peak injury pressure on neurological outcome has been examined in the fluid percussion injury (FPI) model, it is unknown whether differences in rate of rise of the injury waveform modify cellular and physiological changes after TBI. Using a programmable FPI device, we examined juvenile rats subjected to a constant peak pressure at two rates of injury: a standard FPI rate of rise and a faster rate of rise to the same peak pressure. Immediate postinjury assessment identified fewer seizures and relatively brief loss of consciousness after fast‐rise injuries than after standard‐rise injuries at similar peak pressures. Compared with rats injured at standard rise, fewer silver‐stained injured neuronal profiles and degenerating hilar neurons were observed 4–6 hr after fast‐rise FPI. However, 1 week postinjury, both fast‐ and standard‐rise FPI resulted in hilar cell loss and enhanced perforant path‐evoked granule cell field excitability compared with sham controls. Notably, the extent of neuronal loss and increase in dentate excitability were not different between rats injured at fast and standard rates of rise to peak pressure. Our data indicate that reduced cellular damage and improved immediate neurological outcome after fast rising primary concussive injuries mask the severity of the subsequent cellular and neurophysiological pathology and may be unreliable as a predictor of prognosis. © 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.
Influence of antioxidant compounds, total sugars and genetic background on the chilling injury susceptibility of a non‐melting peach (Prunus persica (L.) Batsch) progeny
Authors: Abidi Walid , Cantín Celia M , Jiménez Sergio , Giménez Rosa , Moreno María Ángeles , Gogorcena Yolanda
Published: May 2014

BACKGROUND

To identify genotypes with good organoleptic properties, antioxidant‐rich content and low susceptibility to chilling injury (CI), fruits from 130 peach cultivars were studied over three consecutive years. Pomological traits, l‐ascorbic acid, flavonoids, total phenolics, relative antioxidant capacity (RAC) and sugars were determined. Major symptoms of CI developed at 5 °C, such as leatheriness, flesh browning, bleeding and loss of flavor, were evaluated.

RESULTS

The population exhibited wide phenotypic variation in agronomic and biochemical traits. Six genotypes with high total phenolics, RAC, flavonoids and total sugars were selected. The progeny also showed variability for all evaluated CI symptoms, and 16 genotypes showed considerably lower susceptibility to CI. After 2 weeks of cold storage, leatheriness and bleeding were the main CI symptoms observed, whereas flesh browning was predominant after 4 weeks.

CONCLUSION

It was possible to find varieties with high phenolic concentration and relatively low or intermediate CI susceptibility (22, 33, 68, 80, 81, 96 and 120). However, the correlations observed between CI and phenolic contents highlight their potential influence on susceptibility to internal browning. This relationship should be considered in the current breeding programs to select cultivars with high bioactive compound contents, health‐enhancing properties and good postharvest performance. © 2014 Society of Chemical Industry
Numerical analysis of spiral oil wedge sleeve bearing including cavitation and wall slip effects
Authors: Wang Li‐li , Lu Chang‐hou
Published: May 2014

The modified Reynolds equation is established on the basis of critical shear stress model, in which the circumferential and axial wall slip of sleeve and journal surface is considered. Cavitation is treated using modified Elrod algorithm that simplifies the solution of modified Reynolds equation in the full‐film region. The modified Reynolds equations considering wall slip and cavitation effect for two‐dimensional sleeve bearing are established. The results show that wall slip decreases oil film pressure, carrying capacity, friction drag and temperature rise but increases end leakage and cavitation region. The obtained results using the mass‐conserving boundary condition are compared with the Reynolds boundary condition. Copyright © 2014 John Wiley & Sons, Ltd.
Acute and chronic cadmium exposure promotes E‐cadherin degradation in MCF7 breast cancer cells
Authors: Ponce Esmeralda , Louie Maggie C. , Sevigny Mary B.
Published: May 2014

Cadmium is an environmental carcinogen that usually enters the body at minute concentrations through diet or cigarette smoke and bioaccumulates in soft tissues. In past studies, cadmium has been shown to contribute to the development of more aggressive cancer phenotypes including increased cell migration and invasion. This study aims to determine if cadmium exposure—both acute and chronic—contributes to breast cancer progression by interfering with the normal functional relationship between E‐cadherin and β‐catenin. An MCF7 breast cancer cell line (MCF7‐Cd) chronically exposed to 10−7 M CdCl2 was previously developed and used as a model system to study chronic exposures, whereas parental MCF7 cells exposed to 10−6 M CdCl2 for short periods of time were used to study acute exposures. Cadmium exposure of MCF7 cells led to the degradation of the E‐cadherin protein via the ubiquitination pathway. This resulted in fewer E‐cadherin/β‐catenin complexes and the relocation of active β‐catenin to the nucleus, where it interacted with transcription factor TCF‐4 to modulate gene expression. Interestingly, only cells chronically exposed to cadmium showed a significant decrease in the localization of β‐catenin to the plasma membrane and an increased distance between cells. Our data suggest that cadmium exposure promotes breast cancer progression by (1) down‐regulating E‐cadherin, thus decreasing the number of E‐cadherin/β‐catenin adhesion complexes, and (2) enhancing the nuclear translocation of β‐catenin to increase expression of cancer‐promoting proteins (i.e., c‐Jun and cyclin D1). © 2014 Wiley Periodicals, Inc.
Biased Agonism at G Protein‐Coupled Receptors: The Promise and the Challenges—A Medicinal Chemistry Perspective
Authors: Shonberg Jeremy , Lopez Laura , Scammells Peter J. , Christopoulos Arthur , Capuano Ben , Lane J. Robert
Published: May 2014

Historically, determination of G protein‐coupled receptor (GPCR) ligand efficacy has often been restricted to identifying the ligand as an agonist or antagonist at a given signaling pathway. This classification was deemed sufficient to predict compound efficacy at all signaling endpoints, including the therapeutically relevant one(s). However, it is now apparent that ligands acting at the same GPCR can stabilize multiple, distinct, receptor conformations linked to different functional outcomes. This phenomenon, known as biased agonism, stimulus bias, or functional selectivity offers the opportunity to separate on‐target therapeutic effects from side effects through the design of drugs that show pathway selectivity. However, the medicinal chemist faces numerous challenges to develop biased ligands, including the detection and quantification of biased agonism. This review summarizes the current state of the field of research into biased agonism at GPCRs, with a particular focus on efforts to relate biased agonism to ligand structure.
Water–fat separation from a single spatiotemporally encoded echo based on nominal k‐space peaking and joint regularized estimation
Authors: Chen Ying , Cai Congbo , Zhong Jianhui , Chen Zhong
Published: May 2014

Purpose

To present a new high‐resolution single‐point water–fat separation algorithm based on the spatiotemporally encoded chemical shift imaging technique.

Theory

Identifying water and fat peaks on the ensemble of the nominal k‐space profiles of all spatiotemporally encoded lines enables evaluation of the mean off‐resonance frequencies of the two components. With utilization of the spatial smoothness and filtering regularizations, the water/fat profiles can be discriminated with twice joint linear least squares estimations line‐by‐line.

Methods

The effectiveness of the proposed algorithm was assessed by experiments on oil‐water phantoms and in vivo in rats at 7T using a spatiotemporally encoded variant of the multishot spin‐echo sequence. The results were compared with those obtained from previously proposed 1‐point Dixon, 2‐point Dixon, and 3‐point IDEAL methods.

Results

The results demonstrate that the new technique can achieve high‐quality water–fat separations, comparable in signal‐to‐noise ratio and contrast to the multipoint methods and is more robust in cases when large areas of low signals or motion artifacts jeopardize the results from the 1‐point Dixon method.

Conclusions

The proposed technique is potentially a new viable alternative for single‐point water–fat separation. Magn Reson Med 73:1441–1449, 2015. © 2014 Wiley Periodicals, Inc.
Gemeinsam gewinnen
Authors: Kühne Andreas , Servatius Hans‐Gerd , Volkmann Tim
Published: May 2014

Ein neues Produkt, eine Innovation, entsteht, wenn das Wissen um einen Bedarf mit den Lösungen für dessen Erfüllung verknüpft wird. Arbeitet ein Unternehmen offen mit seinen Kunden und deren Kunden zusammen, erhöht dies die Zahl der Verknüpfungen und führt so zu einem besseren Produkt.
Motivation for alumni donations: a social identity perspective on the role of branding in higher education
Authors: Stephenson Amber L. , Bell Nikki
Published: May 2014

As a result of decreasing government funds and increasing competition, institutions of higher education have propelled themselves into business practices such as branding. Despite the growing literature on branding in higher education, there is little research on the relationship between alumni donor motivations and the university brand. This study explores donor motivations from social identity and self‐congruity theoretical perspectives. The authors used zero‐inflated negative binomial regression to assess the relationship between identification and count of donations. The results showed that if the level of identification with the university increased, the expected number of donations would also increase. The study further assessing the “zeros” (non‐donors), the results suggested that if an alumnus were to identify with the university, he would be 43% less likely to be “certain zero” (definitive non‐donor) and would find a way to give money. Additionally, the authors analyzed responses about why alumni donate and why they choose not to donate. The authors offered observations on the basis of respondent commentary and also raised the question of what happens when university branding efforts conflict with the perceptions of a large stakeholder group such as alumni.

Copyright © 2014 John Wiley & Sons, Ltd.
High dose alkylator therapy for extracranial malignant rhabdoid tumors in children
Authors: Venkatramani Rajkumar , Shoureshi Poone , Malvar Jemily , Zhou Shengmei , Mascarenhas Leo
Published: April 2014

Background

Extracranial malignant rhabdoid tumor (MRT) is a rare pediatric cancer with a poor prognosis. The kidney is the most common site. Isolated reports have shown improvements in patient survival, but no specific treatment regimen has shown efficacy over others.

Procedure

Retrospective review of patients diagnosed with extracranial MRT at Children's Hospital Los Angeles between 1983 and 2012.

Results

The median age at presentation for the 21 patients was 13 months (range, 0–108 months). Ten patients had renal primary tumors. The median time to progression was 4 months (range, 0.4–7 months). The 5‐year event free survival (EFS) and overall survival (OS) of the entire cohort was 38 ± 10.6%. After 2002, patients diagnosed with extracranial MRT were administered a chemotherapy regimen of vincristine, doxorubicin and high dose cyclophosphamide (VDC). The OS for the patients diagnosed before and after 2002 were 20 ± 12% and 54 ± 15%, respectively. Of the 13 patients who received VDC containing regimen, eight patients achieved a complete radiological remission; five of these patients are long‐term survivors. Four patients who received autologous bone marrow transplantation were alive at last follow‐up. All patients with unresectable primary tumors died. Patients who had disease progression or relapse did not survive.

Conclusions

Patients with extracranial MRT have a poor prognosis. Treatment with high dose alkylator therapy followed by consolidation with high dose chemotherapy and autologous bone marrow transplant for those patients in radiographic complete remission appears to have a beneficial effect on survival. Pediatr Blood Cancer 2014; 61:1357–1361. © 2014 Wiley Periodicals, Inc.
Risk and predictors of attempted and completed suicide in patients with hematological malignancies
Authors: Mohammadi Mohammad , Moradi Tahereh , Bottai Matteo , Reutfors Johan , Cao Yang , Smedby Karin E.
Published: April 2014

Background

Hematological malignancies can cause high levels of distress, but few studies have assessed risk of suicidal behavior among these patients.

Methods

We evaluated risk of attempted and completed suicide in a cohort of 46,309 patients diagnosed with malignant lymphoma, myeloma and leukemia in Sweden 1992 to 2009 and 107,736 cancer‐free subjects, using Poisson regression.

Results

In all, 146 suicide attempts and 63 completed suicides occurred during a median follow up of 3.1 years (maximum 19 years). The risk of completed suicide was 3.5‐fold increased among patients with myeloma [incidence rate ratio (IRR) = 3.52, 95% confidence interval (CI) = 2.05−6.03] and 1.9‐fold increased among patients with lymphoma (IRR = 1.87, 95% CI = 1.31−2.67) but not significantly increased among patients with leukemia. Risk of attempted suicide was increased among patients with myeloma (IRR = 2.13, CI = 1.39−3.26) and lymphoma (IRR = 1.34, 95% CI = 1.07−1.69). Both male and female patients were at increased risk of attempted as well as completed suicide. A pre‐malignant history of mental disorders conferred 15‐fold to 30‐fold increased risks, but elevated risks were also observed among patients without such history.

Conclusions

Suicidal actions in patients with hematological malignancies have high suicidal intent, and that subgroups of patients should be monitored for suicidal ideation. Copyright © 2014 John Wiley & Sons, Ltd.
Black holes, the van der Waals gas, compressibility and the speed of sound
Authors: Dolan B.P.
Published: May 2014

We review some recent developments in black hole thermodynamics for asymptotically anti‐de Sitter black holes. Viewing the cosmological constant as a thermodynamic pressure allows a thermodynamic volume to be defined, the thermodynamically conjugate variable to the pressure. The properties of the equation of state can then be studied and a compressibility and a speed of sound is defined for such black holes.
\documentclass{article}\usepackage{amssymb}\pagestyle{empty}\begin{document}$ \mathcal{N} = 2$\end{document} string amplitudes and the Omega background
Authors: Florakis I. , Zein Assi A.
Published: May 2014

We review recent work [1,2] on obtaining a realisation of the Ω‐background in terms of a special series of higher‐derivative generalised F‐terms in the effective \documentclass{article}\usepackage{amssymb}\pagestyle{empty}\begin{document}$ \mathcal{N} = 2$\end{document} supergravity action. We discuss the motivation behind the identification of these couplings, their relation to the Nekrasov partition function and connect them to a worldsheet approach towards the refined topological string.
Primary Laparotomy is Effective and Safe in the Treatment of Necrotizing Enterocolitis
Authors: Gfroerer Stefan , Fiegel Henning , Schloesser Rolf L. , Rolle Udo
Published: April 2014

Introduction

There is ongoing controversy regarding the surgical treatment of necrotizing enterocolitis (NEC) in infants with extremely low birth weight (ELBW). We hypothesize that primary laparotomy is a safe and effective treatment for all infants with surgical NEC.

Methods

We retrospectively compared a group of ELBW infants (<1,000 g, group A, n = 39) with preterm infants (≥1,000 g, group B, n = 18) with surgical NEC during a 4‐year period (10/2008–09/2012). Indications for emergency operation were Bell stages IIIa or IIIb. The main outcome measure was survival. Data were analyzed using Chi squared test and Spearman’s rank correlation coefficient.

Results

Fifty‐seven patients were included with a gestational age from 24 to 30 weeks in group A and 27–38 weeks in group B. There were no significant differences in Bell stage (IIIa; IIIb) and NEC type (focal; segmental; pannecrosis). The operative techniques were not significantly different between the groups and included resection and stoma formation in 44 of 57 (77 %) patients; resection and anastomosis in 6 of 57 (11 %); and inspection only, followed by withdrawal of care, in 7 of 57 (12 %). Overall mortality was 10 of 57 (17 %) with no significant difference between the groups. The only significant correlation was observed between the length of necrotic bowel and mortality. In total, 7 of 57 infants required repeated surgery after initial treatment. We observed stoma complications in 36 % of the patients in group A and 21 % in group B without the need of stoma revision. All stomas were successfully closed at the time of the study. One of 44 patients with stoma closure required a relaparotomy due to bowel obstruction.

Conclusions

Early primary laparotomy is safe and effective for the management of surgical NEC in ELBW infants. Outcome of affected infants is not influenced by age or weight at surgery but by the length of necrotic bowel.
Characterising and developing vocational mathematical knowledge
Authors: Bakker A.
Published: April 2014

In this introductory article, I argue why this special issue focuses on the question of how the mathematical knowledge required at work can be characterised and developed in vocational education and workplace training. After some words on the importance of this subfield of mathematics education and the need to rethink metaphors of learning in this area, I summarise the structure of the special issue and highlight a few main points raised in the various contributions.
Cardiac thin filament regulation and the Frank–Starling mechanism
Authors: Kobirumaki-Shimozawa Fuyu , Inoue Takahiro , Shintani Seine A. , Oyama Kotaro , Terui Takako , Minamisawa Susumu , Ishiwata Shin’ichi , Fukuda Norio
Published: April 2014

The heart has an intrinsic ability to increase systolic force in response to a rise in ventricular filling (the Frank–Starling law of the heart). It is widely accepted that the length dependence of myocardial activation underlies the Frank–Starling law of the heart. Recent advances in muscle physiology have enabled the identification of the factors involved in length-dependent activation, viz., titin (connectin)-based interfilament lattice spacing reduction and thin filament “on–off” regulation, with the former triggering length-dependent activation and the latter determining the number of myosin molecules recruited to thin filaments. Patients with a failing heart have demonstrated reduced exercise tolerance at least in part via depression of the Frank–Starling mechanism. Recent studies revealed that various mutations occur in the thin filament regulatory proteins, such as troponin, in the ventricular muscle of failing hearts, which consequently alter the Frank–Starling mechanism. In this article, we review the molecular mechanisms of length-dependent activation, and the influence of troponin mutations on the phenomenon.
Obstetric care in a migrant population with free access to health care
Authors: Almeida Lígia M. , Santos Cristina C. , Caldas José P. , Ayres‐de‐Campos Diogo , Dias Sónia
Published: May 2014

Objective

To evaluate differences in obstetric care between immigrant and native women in a country with free access to health care.

Methods

A cross‐sectional study was carried out of immigrant mothers delivering in one of the four public hospitals in the Porto, Portugal, metropolitan area between February and December 2012. The comparison group included native Portuguese mothers who delivered in the same institutions. The participants (89 immigrant mothers and 188 Portuguese mothers) were recruited by telephone and completed a written questionnaire during a home visit.

Results

Immigrant women were more likely to have their first pregnancy appointment after 12 weeks of pregnancy (27.0% vs 14.4%, P = 0.011) and to have fewer than three prenatal visits (2.2% vs 0.0%, P < 0.001). They were also more likely to have had a cesarean delivery (48.3% vs 31.4%, P = 0.023), perineal laceration (48.8% vs 11.6%, P < 0.001), or postpartum hemorrhage (33.5% vs 12.3%, P < 0.001).

Conclusion

Migrants were more prone to late prenatal care and to intrapartum complications. Unsatisfactory interactions with healthcare staff may play an important role in these findings.
Relationship Between the Type and Amount of Physical Activity and Low Back Pain in Koreans Aged 50 Years and Older
Authors: Kim Won , Jin Young Soo , Lee Choon Sung , Hwang Chang Ju , Lee Sang Yoon , Chung Sun G. , Choi Kyoung Hyo
Published: April 2014

Objectives

To examine the association between the type and amount of physical activity (PA) and low back pain (LBP) in people aged ≥50 years.

Design

Cross‐sectional study.

Setting

A nationwide survey.

Participants

Data were obtained from the Fifth Korea National Health and Nutrition Examination Survey, which was conducted in 2010 and 2011. Overall, 1796 men and 2198 women aged ≥50 years were included.

Methods

PA was categorized as vigorous, moderate, walking, strength exercises, or flexibility exercises. The total amount of PA was presented as quartiles of the total metabolic equivalent (MET)‐minutes/week based on the PA questionnaire. Multivariate logistic regression analysis was performed to examine associations between LBP and the type and amount of PA.

Main Outcome Measurements

Odds ratio for LBP according to the type of PA and the quartiles of the total MET‐minutes/week.

Results

After adjusting for age and body mass index, vigorous and moderate PA were associated with an increased risk of LBP in both men and women, whereas strength exercises were associated with a reduced risk of LBP. These associations were maintained after adjusting for all potential confounders. Subgroup analysis according to age revealed that these trends were most significantly demonstrated in women aged ≥65 years. The PA quartiles for total MET‐minutes/week for men showed a U‐shaped association with LBP, whereas only the fourth PA quartile for women showed an increased risk of LBP compared with the second quartile.

Conclusions

These results suggest that both the type and amount of PA affect the development of LBP in people aged ≥50 years and thus activity modification might be helpful for prevention and management of LBP.
Kim Jong-il’s military-first politics and beyond: Military control mechanisms and the problem of power succession
Authors: Woo Jongseok
Published: April 2014

Military-first politics has been at the heart of the unexpected regime stability in North Korea under Kim Jong-il and his son Jong-un. This article analyzes Kim Jong-il’s military-first politics as a strategic choice for regime survival, in which the locus of political power switched from the party to the military. At the same time, Kim Jong-il formulated a complex system of circumventing the possibility of the armed forces’ political domination, including personalistic control using sticks and carrots, fortifying security and surveillance institutions, and compartmentalizing the security institutions for intra- and inter-organizational checks and balances to prevent the emergence of organized opposition to the regime. Although an effective short-term solution, military-first politics could never be a long-term strategy for building gangseongdaeguk (a powerful and prosperous nation). The current Kim Jong-un regime needs to conduct sweeping reforms to address dire economic difficulties, which might result in a departure from his father’s legacy and downgrade the military’s power. In this process, the current regime’s (in)stability will depend on how it maintains a balance between revoking military-first politics and preserving the armed forces’ allegiance.