bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do eating disorders in parents predict eating disorders in children? Evidence from a Swedish cohort
Authors: Bould H. , Sovio U. , Koupil I. , Dalman C. , Micali N. , Lewis G. , Magnusson C. 
Published: January 2015

ObjectiveWe investigated whether parental eating disorders (ED) predict ED in children, using a large multigeneration register‐based sample.MethodWe used a subset of the Stockholm Youth Cohort born 1984–1995 and resident in Stockholm County in 2001–2007 (N = 286 232), The exposure was a diagnosed eating disorder in a parent; the outcome was any eating disorder diagnosis in their offspring, given by a specialist clinician, or inferred from an appointment at a specialist eating disorder clinic. A final study sample of 158 697 (55.4%) had data on these variables and confounding factors and contributed a total of 886 241 person years to the analysis.ResultsWe found good evidence in support of the hypothesis that ED in either parent are independently associated with ED in their female children (HR 1.97 (95% CI: 1.17–3.33), P = 0.01) and that ED in mothers are independently associated with ED in their female children (HR 2.35 (95% CI: 1.39–3.97) P = 0.001). Numbers were too low to permit separate analysis of ED in parents and their male children.ConclusionEating disorders in parents were associated with ED in children. This study adds to our knowledge about the intergenerational transmission of ED, which will help identify high‐risk groups and brings about the possibility of targeted prevention.
Malondialdehyde, superoxide dismutase and melatonin levels in gingival crevicular fluid of aggressive and chronic periodontitis patients
Authors: Ghallab NA , Hamdy E , Shaker OG 
Published: January 2015

AbstractBackgroundThe aim of this study was to investigate malondialdehyde (MDA), superoxide dismutase (SOD) and melatonin levels in the gingival crevicular fluid (GCF) of patients with chronic periodontitis (CP) and generalized aggressive periodontitis (GAgP) as biomarkers for oxidative stress.MethodsThe study comprised 65 subjects: 15 healthy individuals, 25 CP patients and 25 GAgP patients. Plaque index, gingival index, pocket depth, clinical attachment level measurements and GCF samples were obtained from all subjects. MDA, SOD and melatonin levels were determined utilizing enzyme‐linked immunosorbent assay.ResultsGCF‐MDA levels were significantly higher in the GAgP group compared to the CP and control groups (p < 0.001) and significantly higher in the CP group than the C group (p < 0.001). SOD and melatonin GCF levels were significantly higher in the control than the GAgP and CP groups (p < 0.05), and significantly lower in the GAgP than the CP group (p < 0.05). The CP group demonstrated a significant negative correlation between GCF‐MDA and melatonin concentrations. A positive correlation was observed between SOD and CAL in the CP group and PD in the GAgP group.ConclusionsMDA, melatonin and SOD could be considered as biomarkers for oxidative stress in periodontal diseases and might be useful diagnostic aids in distinguishing CP and GAgP patients.
Can e‐learning system enhance learning culture in the workplace? A comparison among companies in South Korea
Authors: Yoo Sun Joo , Huang Wenhao David 
Published: January 2015

AbstractHow organizations need to act in order to develop their learning capacities has always been a focal interest of research and practice in the workplace. In practice, an e‐learning system is often utilized to foster professional development as it is capable of delivering information and knowledge to individuals across organizations. However, the effect of e‐learning systems on fostering the development of learning organizations in South Korean companies remains unsubstantiated by empirical research. Hence, in this study, a total of 327 datasets from three Korean companies (A, B and C) were analyzed to investigate this research question: can utilizing an e‐learning system accelerate the process of companies becoming learning organizations? The results showed that only the e‐learning systems of Company A and Company C, but not of Company B, facilitated the development of learning organizations. The study concluded that employees' acceptance levels toward e‐learning systems must be considered in order to effectively promote long‐term implementation of e‐learning systems that would lead to the development of learning organizations.
Molecular determinants of positive allosteric modulation of the human metabotropic glutamate receptor 2
Authors: Farinha A , Lavreysen H , Peeters L , Russo B , Masure S , Trabanco A A , Cid J , Tresadern G 
Published: January 2015

Background and PurposeThe activation of the metabotropic glutamate receptor 2 (mGlu2) reduces glutamatergic transmission in brain regions where excess excitatory signalling is implicated in disorders such as anxiety and schizophrenia. Positive allosteric modulators (PAMs) can provide a fine‐tuned potentiation of these receptors' function and are being investigated as a novel therapeutic approach. An extensive set of mutant human mGlu2 receptors were used to investigate the molecular determinants that are important for positive allosteric modulation at this receptor.Experimental ApproachSite‐directed mutagenesis, binding and functional assays were employed to identify amino acids important for the activity of nine PAMs. The data from the radioligand binding and mutagenesis studies were used with computational docking to predict a binding mode at an mGlu2 receptor model based on the recent structure of the mGlu1 receptor.Key ResultsNew amino acids in TM3 (R635, L639, F643), TM5 (L732) and TM6 (W773, F776) were identified for the first time as playing an important role in the activity of mGlu2 PAMs.Conclusions and ImplicationsThis extensive study furthers our understanding of positive allosteric modulation of the mGlu2 receptor and can contribute to improved future design of mGlu2 PAMs.
Beyond traditional pharmacology: new tools and approaches
Authors: Gurevich E V , Gurevich V V 
Published: January 2015

Traditional pharmacology is defined as the science that deals with drugs and their actions. While small molecule drugs have clear advantages, there are many cases where they have proved to be ineffective, prone to unacceptable side effects, or where due to a particular disease aetiology they cannot possibly be effective. A dominant feature of the small molecule drugs is their single mindedness: they provide either continuous inhibition or continuous activation of the target. Because of that, these drugs tend to engage compensatory mechanisms leading to drug tolerance, drug resistance or, in some cases, sensitization and consequent loss of therapeutic efficacy over time and/or unwanted side effects. Here we discuss new and emerging therapeutic tools and approaches that have potential for treating the majority of disorders for which small molecules are either failing or cannot be developed. These new tools include biologics, such as recombinant hormones and antibodies, as well as approaches involving gene transfer (gene therapy and genome editing) and the introduction of specially designed self‐replicating cells. It is clear that no single method is going to be a ‘silver bullet’, but collectively, these novel approaches hold promise for curing practically every disorder.Linked ArticlesThis article is part of a themed section on 5th BPS Focused Meeting on Cell Signalling. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐13
Divergent effects of the ‘biased’ 5‐HT1A receptor agonists F15599 and F13714 in a novel object pattern separation task
Authors: van Goethem N P , Schreiber R , Newman‐Tancredi A , Varney M , Prickaerts J 
Published: January 2015

Background and PurposePattern separation, that is, the formation of distinct representations from similar inputs, is an important hippocampal process implicated in cognitive domains like episodic memory. A deficit in pattern separation could lead to memory impairments in several psychiatric and neurological disorders. Hence, mechanisms by which pattern separation can be increased are of potential therapeutic interest.Experimental approach5‐HT1A receptors are involved in spatial memory. Herein we tested the ‘biased’ 5‐HT1A receptor agonists F15599, which preferentially activates post‐synaptic heteroreceptors, and F13714, which preferentially activates raphe‐located autoreceptors, in rats in a novel spatial task assessing pattern separation, the object pattern separation (OPS) task.Key ResultsThe acetylcholinesterase inhibitor donepezil, which served as a positive control, significantly improved spatial pattern separation at a dose of 1 mg·kg−1, p.o. F15599 increased pattern separation at 0.04 mg·kg−1, i.p., while F13714 decreased pattern separation at 0.0025 mg·kg−1, i.p. The selective 5‐HT1A receptor antagonist WAY‐100635 (0.63 mg·kg−1, s.c.) counteracted the effects of both agonists. These data suggest that acute preferential activation of post‐synaptic 5‐HT1A heteroreceptors improves spatial pattern separation, whereas acute preferential activation of raphe‐located 5‐HT1A autoreceptors impairs performance.Conclusions and ImplicationsWe successfully established and validated a novel, simple and robust OPS task and observed a diverging profile of response with ‘biased’ 5‐HT1A receptor agonists based on their targeting of receptors in distinct brain regions. Our data suggest that the post‐synaptic 5‐HT1A receptor consists of a potential novel molecular target to improve pattern separation performance.
GPCR‐mediated EGF receptor transactivation regulates TRPV4 action in the vasculature
Authors: Saifeddine Mahmoud , El‐Daly Mahmoud , Mihara Koichiro , Bunnett Nigel W , McIntyre Peter , Altier Christophe , Hollenberg Morley D , Ramachandran Rithwik 
Published: January 2015

Background and PurposeTransient receptor potential vanilloid‐4 (TRPV4) is a calcium‐permeant ion channel that is known to affect vascular function. The ability of TRPV4 to cause a vasoconstriction in blood vessels has not yet been mechanistically examined. Further in neuronal cells, TRPV4 signalling can be potentiated by GPCR activation. Thus, we studied the mechanisms underlying the vascular contractile action of TRPV4 and the GPCR‐mediated potentiation of such vasoconstriction, both of which are as yet unappreciated aspects of TRPV4 function.Experimental ApproachThe mechanisms of TRPV4‐dependent regulation of vascular tone in isolated mouse aortae were studied using wire myography. TRPV4‐dependent calcium signalling and prostanoid production was studied in cultured human umbilical vein endothelial cells (HUVECs).Key ResultsIn addition to the well‐documented vasorelaxation response triggered by TRPV4 activation, we report here a TRPV4‐triggered vasoconstriction in the mouse aorta that involves a COX‐generated Tx receptor (TP) agonist that acts in a MAPK and Src kinase signalling dependent manner. This constriction is potentiated by activation of the GPCRs for angiotensin (AT1 receptors) or proteinases (PAR1 and PAR2) via transactivation of the EGF receptor and a process involving PKC. TRPV4‐dependent vascular contraction can be blocked by COX inhibitors or with TP antagonists. Further, TRPV4 activation in HUVECs stimulated Tx release as detected by an elisa.Conclusion and ImplicationsWe conclude that the GPCR potentiation of TRPV4 action and TRPV4‐dependent Tx receptor activation are important regulators of vascular function and could be therapeutically targeted in vascular diseases.
Glial cell line‐derived neurotrophic factor‐mediated enhancement of noradrenergic descending inhibition in the locus coeruleus exerts prolonged analgesia in neuropathic pain
Authors: Kimura M , Sakai A , Sakamoto A , Suzuki H 
Published: January 2015

Background and PurposeThe locus coeruleus (LC) is the principal nucleus containing the noradrenergic neurons and is a major endogenous source of pain modulation in the brain. Glial cell line‐derived neurotrophic factor (GDNF), a well‐established neurotrophic factor for noradrenergic neurons, is a major pain modulator in the spinal cord and primary sensory neurons. However, it is unknown whether GDNF is involved in pain modulation in the LC.Experimental ApproachRats with chronic constriction injury (CCI) of the left sciatic nerve were used as a model of neuropathic pain. GDNF was injected into the left LC of rats with CCI for 3 consecutive days and changes in mechanical allodynia and thermal hyperalgesia were assessed. The α2‐adrenoceptor antagonist yohimbine was injected intrathecally to assess the involvement of descending inhibition in GDNF‐mediated analgesia. The MEK inhibitor U0126 was used to investigate whether the ERK signalling pathway plays a role in the analgesic effects of GDNF.Key ResultsBoth mechanical allodynia and thermal hyperalgesia were attenuated 24 h after the first GDNF injection. GDNF increased the noradrenaline content in the dorsal spinal cord. The analgesic effects continued for at least 3 days after the last injection. Yohimbine abolished these effects of GDNF. The analgesic effects of GDNF were partly, but significantly, inhibited by prior injection of U0126 into the LC.Conclusions and ImplicationsGDNF injection into the LC exerts prolonged analgesic effects on neuropathic pain in rats by enhancing descending noradrenergic inhibition.
GPCR dimerization in brainstem nuclei contributes to the development of hypertension
Authors: Sun Gwo‐Ching , Ho Wen‐Yu , Chen Bo‐Rung , Cheng Pei‐Wen , Cheng Wen‐Han , Hsu Mei‐Chi , Yeh Tung‐Chen , Hsiao Michael , Lu Pei‐Jung , Tseng Ching‐Jiunn 
Published: January 2015

Background and Purposeμ‐Opioid receptors, pro‐opiomelanocortin and pro‐enkephalin are highly expressed in the nucleus tractus solitarii (NTS) and μ receptor agonists given to the NTS dose‐dependently increased BP. However, the molecular mechanisms of this process remain unclear. In vitro, μ receptors heterodimerize with α2A‐adrenoceptors. We hypothesized that α2A‐adrenoceptor agonists would lose their depressor effects when their receptors heterodimerize in the NTS with μ receptors.Experimental ApproachWe microinjected μ‐opioid agonists and antagonists into the NTS of rats and measured changes in BP. Formation of μ receptor/α2A‐adrenoceptor heterodimers was assessed with immunofluorescence and co‐immunoprecipitation methods, along with proximity ligation assays.Key ResultsImmunofluorescence staining revealed colocalization of α2A‐adrenoceptors and μ receptors in NTS neurons. Co‐immunoprecipitation revealed interactions between α2A‐adrenoceptors and μ receptors. In situ proximity ligation assays confirmed the presence of μ receptor/α2A‐adrenoceptor heterodimers in the NTS. Higher levels of endogenous endomorphin‐1 and μ receptor/α2A‐adrenoceptor heterodimers were found in the NTS of hypertensive rats, than in normotensive rats. Microinjection of the μ receptor agonist [D‐Ala2, MePhe4, Gly5‐ol]‐enkephalin (DAMGO), but not that of the α2A‐adrenoceptor agonist guanfacine, into the NTS of normotensive rats increased μ receptor/α2A‐adrenoceptor heterodimer formation and BP elevation. The NO‐dependent BP‐lowering effect of α2A‐adrenoceptor agonists was blunted following increased formation of μ receptor/α2A‐adrenoceptor heterodimers in the NTS of hypertensive rats and DAMGO‐treated normotensive rats.Conclusions and ImplicationsIncreases in endogenous μ receptor agonists in the NTS induced μ receptor/α2A‐adrenoceptor heterodimer formation and reduced the NO‐dependent depressor effect of α2A‐adrenoceptor agonists. This process could contribute to the pathogenesis of hypertension.
9‐Phenanthrol inhibits recombinant and arterial myocyte TMEM16A channels
Authors: Burris Sarah K , Wang Qian , Bulley Simon , Neeb Zachary P , Jaggar Jonathan H 
Published: January 2015

Background and PurposeIn arterial smooth muscle cells (myocytes), intravascular pressure stimulates membrane depolarization and vasoconstriction (the myogenic response). Ion channels proposed to mediate pressure‐induced depolarization include several transient receptor potential (TRP) channels, including TRPM4, and transmembrane protein 16A (TMEM16A), a Ca2+‐activated Cl− channel (CaCC). 9‐Phenanthrol, a putative selective TRPM4 channel inhibitor, abolishes myogenic tone in cerebral arteries, suggesting that either TRPM4 is essential for pressure‐induced depolarization, upstream of activation of other ion channels or that 9‐phenanthrol is non‐selective. Here, we tested the hypothesis that 9‐phenanthrol is also a TMEM16A channel blocker, an ion channel for which few inhibitors have been identified.Experimental ApproachPatch clamp electrophysiology was used to measure rat cerebral artery myocyte and human recombinant TMEM16A (rTMEM16A) currents or currents generated by recombinant bestrophin‐1, another Ca2+‐activated Cl− channel, expressed in HEK293 cells.Key Results9‐Phenanthrol blocked myocyte TMEM16A currents activated by either intracellular Ca2+ or Eact, a TMEM16A channel activator. In contrast, 9‐phenanthrol did not alter recombinant bestrophin‐1 currents. 9‐Phenanthrol reduced arterial myocyte TMEM16A currents with an IC50 of ∼12 μM. Cell‐attached patch recordings indicated that 9‐phenanthrol reduced single rTMEM16A channel open probability and mean open time, and increased mean closed time without affecting the amplitude.Conclusions and ImplicationsThese data identify 9‐phenanthrol as a novel TMEM16A channel blocker and provide an explanation for the previous observation that 9‐phenanthrol abolishes myogenic tone when both TRPM4 and TMEM16A channels contribute to this response. 9‐Phenanthrol may be a promising candidate from which to develop TMEM16A channel‐specific inhibitors.
Easy as ABCABC: Abstract Language Facilitates Performance on a Concrete Patterning Task
Authors: Fyfe Emily R. , McNeil Nicole M. , Rittle‐Johnson Bethany 
Published: January 2015

The labels used to describe patterns and relations can influence children's relational reasoning. In this study, 62 preschoolers (Mage = 4.4 years) solved and described eight pattern abstraction problems (i.e., recreated the relation in a model pattern using novel materials). Some children were exposed to concrete labels (e.g., blue‐red‐blue‐red) and others were exposed to abstract labels (e.g., A‐B‐A‐B). Children exposed to abstract labels solved more problems correctly than children exposed to concrete labels. Children's correct adoption of the abstract language into their own descriptions was particularly beneficial. Thus, using concrete learning materials in combination with abstract representations can enhance their utility for children's performance. Furthermore, abstract language may play a key role in the development of relational thinking.
Survival outcome of patients with nasopharyngeal carcinoma: a nationwide analysis of 13 407 patients in Taiwan
Authors: Huang W.‐Y. , Lin C.‐L. , Lin C.‐Y. , Jen Y.‐M. , Lo C.‐H. , Sung F.‐C. , Kao C.‐H. 
Published: January 2015

ObjectivesWe reported the contemporary survival outcome of patients with nasopharyngeal carcinoma (NPC) and analysed the factors affecting survival.DesignA retrospective cohort study.SettingA nationwide population‐based study in Taiwan.ParticipantsWe identified 13 407 patients with newly diagnosed NPC from 2002 to 2010.Material and MethodsThe multivariate Cox proportional hazards model was performed to measure the mortality‐association risk factor in patients with NPC after adjusting for NPC treatment and socio‐demographic characteristics.ResultsThe 1‐, 2‐, 5‐ and 8‐year overall survival (OS) rates were 89.6%, 80.4%, 65.2% and 56.5%, respectively. The factors associated with mortality risk were sex (men versus women, HR  =  1.45), age (>60 versus ≤ 40 years, HR  =  3.61), geographic region of residence (eastern Taiwan versus northern Taiwan HR   =   1.39), income (<15 840 versus >25  000, HR   =   1.87) and treatment modality (chemotherapy alone versus radiotherapy alone, HR   =   2.25).ConclusionThe contemporary 5‐year OS rate was 65.2% in Taiwan. Male patients, old age, residing in eastern Taiwan, low income and receiving chemotherapy alone were independent predictors for poor OS.
Fascin expression in cholesteatoma: correlation with destruction of the ossicular chain and extent of disease
Authors: Binnetoglu A. , Sari M. , Baglam T. , Erbarut Seven I. , Yumusakhuylu A.C. , Topuz M.F. , Batman C. 
Published: January 2015

ObjectiveFascin is an actin‐bundling protein found in cell membrane protrusions and increases cell motility. The expression of fascin in epithelial neoplasms has been described only recently. No data are available concerning the role of this protein in invasive cholesteatoma. Thus, we investigated the expression of fascin in cholesteatoma tissue and the relationship between fascin expression and intraoperative evaluation of the destruction of the ossicular chain and extent of disease.MethodCholesteatoma specimens of 28 patients and external auditory canal (EAC) skin specimens of the same patients (as the control group) were collected from mastoidectomies. Immunohistochemical technique was used to investigate the fascin expression in all cholesteatoma tissues and EAC skin specimens. Immunohistochemical staining was assessed semiquantitatively based on the thickness of epithelium. SPSS software version 16.0 (SPSS Inc., Chicago, IL, USA) was performed to statistically analyse the relationships between fascin expression and intraoperative evaluation destruction of ossicular chain and extent of the disease.ResultsImmunohistochemically, there was no or very low fascin expression observed in normal epithelial cells of EAC skin, while expressed in cholesteatoma tissue. Also, fascin expression in cholesteatoma tissues was significantly correlated with destruction of ossicular chain and extent of the disease.ConclusionsFascin expression is usually found in cholesteatoma epithelium and is correlated with destruction of the ossicular chain and extent of disease. Considering all of the correlations between the clinical and histopathological findings, ‘fascin immunoexpression scoring’ may be used for histological grading of cholesteatoma.
Melatonin potentiates cisplatin‐induced apoptosis and cell cycle arrest in human lung adenocarcinoma cells
Authors: Plaimee P. , Weerapreeyakul N. , Barusrux S. , Johns N. P. 
Published: January 2015

AbstractObjectivesMelatonin produces anti‐cancer effects via several mechanisms, including by induction of apoptosis. In this way, it has been shown to be of use, in combination with chemotherapeutic drugs, for cancer treatment. The study described here has evaluated effects of melatonin on cytotoxicity, apoptosis and cell cycle arrest induced with the chemotherapeutic agent cisplatin, in human lung adenocarcinoma cisplatin‐sensitive cell line (SK‐LU‐1), which previously had only limit data.Materials and methodsCells of the SK‐LU‐1 line were treated with melatonin alone at 1–5 mm concentration or cisplatin alone 10–200 μm, for 48 h in culture. Cytotoxicity was measured by MTT reduction assay. Apoptosis induction was detected by annexin V/PI staining using flow cytometric analysis and DAPI nuclear staining. Change in mitochondrial membrane potential (ΔΨm) was quantified using DiOC6(3) reagent and activities of caspases‐3/7 were also investigated. DNA fractions were measured using propidium iodide (PI) staining.ResultsMelatonin or cisplatin alone had 50% (IC50) cytotoxicity at 5 mm or 34 μm concentrations respectively. Combination of 1 or 2 mm melatonin and cisplatin significantly augmented cytotoxicity of cisplatin by reducing its IC50 to 11 and 4 μm, respectively. Consistently, combined treatment increased population of apoptotic cells by elevating mitochondrial membrane depolarization, activating caspases‐3/7 and inducing cell cycle arrest in the S phase, compared to treatment with cisplatin alone.ConclusionThese data demonstrate that melatonin enhanced cisplatin‐induced cytotoxicity and apoptosis in SK‐LU‐1 lung cancer cells. SK‐LU‐1 cell population growth inhibition was mediated by cell cycle arrest in the S phase. These findings suggest that melatonin has the potential to be used for NSCLC treatment in combination with a chemotherapeutic agent such as cisplatin.