bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional enhancement of cannabinoid CB1 receptor desensitization in female adolescent rats following repeated Δ9‐tetrahydrocannabinol exposure
Authors: Burston James J , Wiley Jenny L , Craig Abimbola A , Selley Dana E , Sim‐Selley Laura J 
Published: May 2010

BACKGROUND AND PURPOSE Disruption of the substantial re‐organization of the brain during adolescence may be induced by persistent abuse of marijuana. The aim of this study was to determine whether adolescent and adult rats exhibit differential adaptation of brain cannabinoid (CB1) receptors after repeated exposure to Δ9‐tetrahydrocannabinol (THC).EXPERIMENTAL APPROACH Rats of both ages and sexes were dosed with 10 mg kg−1 THC or vehicle twice daily for 9.5 days. Subsequently, CB1 receptor function and density were assessed.KEY RESULTS In all brain regions, THC treatment produced desensitization and down‐regulation of CB1 receptors. While the magnitude of down‐regulation did not differ across groups, greater desensitization was evident in the brains of THC‐treated female adolescent rats for most regions. Adolescent females showed greater desensitization than adult females in the prefrontal cortex, hippocampus, periaqueductal gray (PAG) and ventral midbrain. In contrast, adolescent males exhibited less desensitization in the prefrontal cortex, hippocampus and PAG, an effect opposite to that seen in females. With the exception of the PAG, sex differences were seen only in adolescents, with greater desensitization in the prefrontal cortex, striatum, hippocampus, PAG, and ventral midbrain of females.CONCLUSIONS AND IMPLICATIONS These results suggest that the brains of adolescent females may be particularly vulnerable to disruption of CB1 receptor signalling by marijuana abuse. Alternatively, increased desensitization may reflect protective adaptation. Given the extensive re‐organization of the brain during adolescence, this disruption has potential long‐term consequences for maturation of the endocannabinoid system.
Thymoquinone inhibits proliferation, induces apoptosis and chemosensitizes human multiple myeloma cells through suppression of signal transducer and activator of transcription 3 activation pathway
Authors: Li Feng , Rajendran Peramaiyan , Sethi Gautam 
Published: May 2010

BACKGROUND AND PURPOSE Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) pathway is frequently encountered in several human cancers including multiple myeloma (MM). Thus, agents that suppress STAT3 phosphorylation have a potential for treatment of MM. In the present report, we investigated whether thymoquinone (TQ), the main component isolated from the medicinal plant Nigella sativa, modulated the STAT3 signalling pathway in MM cells.EXPERIMENTAL APPROACH The effect of TQ on both constitutive and IL‐6‐induced STAT3 activation, associated protein kinases, STAT3‐regulated gene products involved in proliferation, survival and angiogenesis, cellular proliferation and apoptosis in MM cells, was investigated.KEY RESULTS We found that TQ inhibited both constitutive and IL‐6‐inducible STAT3 phosphorylation which correlated with the inhibition of c‐Src and JAK2 activation. Vanadate reversed the TQ‐induced down‐regulation of STAT3 activation, suggesting the involvement of a protein tyrosine phosphatase. Indeed, we found that TQ can induce the expression of Src homology‐2 phosphatase 2 that correlated with suppression of STAT3 activation. TQ also down‐regulated the expression of STAT3‐regulated gene products, such as cyclin D1, Bcl‐2, Bcl‐xL, survivin, Mcl‐1 and vascular endothelial growth factor. Finally, TQ induced the accumulation of cells in sub‐G1 phase, inhibited proliferation and induced apoptosis, as indicated by poly ADP ribose polymerase cleavage. TQ also significantly potentiated the apoptotic effects of thalidomide and bortezomib in MM cells.CONCLUSIONS AND IMPLICATIONS Our study has identified STAT3 signalling as a target of TQ and has thus raised its potential application in the prevention and treatment of MM and other cancers.
β‐Arrestin 1 and 2 stabilize the angiotensin II type I receptor in distinct high‐affinity conformations
Authors: Sanni SJ , Hansen JT , Bonde MM , Speerschneider T , Christensen GL , Munk S , Gammeltoft S , Hansen JL 
Published: May 2010

BACKGROUND AND PURPOSE The angiotensin II type 1 (AT1) receptor belongs to family A of 7 transmembrane (7TM) receptors. The receptor has important roles in the cardiovascular system and is commonly used as a drug target in cardiovascular diseases. Interaction of 7TM receptors with G proteins or β‐arrestins often induces higher binding affinity for agonists. Here, we examined interactions between AT1A receptors and β‐arrestins to look for differences between the AT1A receptor interaction with β‐arrestin1 and β‐arrestin2.EXPERIMENTAL APPROACH Ligand‐induced interaction between AT1A receptors and β‐arrestins was measured by Bioluminescence Resonance Energy Transfer 2. AT1A‐β‐arrestin1 and AT1A‐β‐arrestin2 fusion proteins were cloned and tested for differences using immunocytochemistry, inositol phosphate hydrolysis and competition radioligand binding.KEY RESULTS Bioluminescence Resonance Energy Transfer 2 analysis showed that β‐arrestin1 and 2 were recruited to AT1A receptors with similar ligand potencies and efficacies. The AT1A‐β‐arrestin fusion proteins showed attenuated G protein signalling and increased agonist binding affinity, while antagonist affinity was unchanged. Importantly, larger agonist affinity shifts were observed for AT1A‐β‐arrestin2 than for AT1A‐β‐arrestin1.CONCLUSION AND IMPLICATIONS β‐Arrestin1 and 2 are recruited to AT1A receptors with similar ligand pharmacology and stabilize AT1A receptors in distinct high‐affinity conformations. However, β‐arrestin2 induces a receptor conformation with a higher agonist‐binding affinity than β‐arrestin1. Thus, this study demonstrates that β‐arrestins interact with AT1A receptors in different ways and suggest that AT1 receptor biased agonists with the ability to recruit either of the β‐arrestins selectively, would be possible to design.
Darbepoetin‐mediated cardioprotection after myocardial infarction involves multiple mechanisms independent of erythropoietin receptor–common β‐chain heteroreceptor
Authors: Kanellakis Peter , Pomilio Giovanna , Agrotis Alex , Gao Xiaoming , Du Xiao‐Jun , Curtis David , Bobik Alexander 
Published: May 2010

BACKGROUND AND PURPOSEDarbepoetin, a long‐acting erythropoietin derivative, attenuates cardiomyocyte apoptosis and improves short‐term (3 days) cardiac function, but the mechanisms responsible are unknown. We investigated potential mechanisms by which darbepoetin exerts cardioprotection following myocardial infarction in mice and the significance of the erythropoietin receptor (EPOR)–common β‐chain (c‐β‐chain) heteroreceptor.EXPERIMENTAL APPROACHMice underwent 60 min coronary occlusion followed by treatment with vehicle or a single dose of darbepoetin. Effects on gene expression, apoptosis and neutrophil accumulation in infarcted left ventricle were assessed 24 h later. Cardiac function, effects on vascularization and fibrosis were assessed 28 days later. The significance of EPOR–c‐β‐chain heteroreceptor was examined 28 days after infarction using mice deficient in c‐β‐chain.KEY RESULTSTwenty‐four hours after darbepoetin, mRNAs encoding haeme oxygenase‐1 (HO‐1), iNOS and brain natriuretic peptide (BNP) were markedly elevated only in infarcted regions, and the frequency of apoptotic cells attenuated. Inflammation was also attenuated with reductions in neutrophil numbers. Darbepoetin also elevated mRNAs encoding angiogenic factors: placental growth factor, monocyte chemoattractant protein‐1 and interleukin‐1β. Twenty‐eight days after treatment, CD31+ vessels in the infarct zone doubled and fibrosis reduced. Cardiac haemodynamics were improved. Darbepoetin also improved cardiac haemodynamics in c‐β‐chain‐deficient mice, increased HO‐1 and iNOS expression and vessel numbers and attenuated fibrosis.CONCLUSIONS AND IMPLICATIONSDarbepoetin stimulates expression of haeme oxygenase, iNOS, BNP and angiogenic factors specifically in infarcted left ventricle that attenuates inflammation, apoptosis and fibrosis; elevate vessel numbers; and improve cardiac function. The EPOR–c‐β‐chain heteroreceptor is not essential for these effects.
Frequency of Headaches in Children is Influenced by Headache Status in the Mother
Authors: Arruda Marco A. , Guidetti Vincenzo , Galli Federica , Albuquerque Regina C.A.P. , Bigal Marcelo E. 
Published: May 2010

(Headache 2010;50:973‐980)Background.— Migraine aggregates within families. Nonetheless the familial aggregation of chronic daily headaches (CDH) and of episodic headaches of different frequencies has been very poorly studied. Accordingly herein we test the hypothesis that frequency of primary headaches aggregates in the family.Methods.— Sample consisted of 1994 children (5‐12 years) identified in the population. Validated questionnaires were used to interview the parents. Crude and adjusted prevalences of low‐frequency (1‐4 headache days/month), intermediate‐frequency (5‐9 days/month), high‐frequency (10‐14 headache days/month), and CDH (15 or more headache days/month) in children were calculated as a function of headaches in the mother.Results.— Frequency of headaches in the mother predicted frequency of headaches in the children; when the mother had low frequency headaches, the children had an increased chance to have low or intermediate headache frequency (relative risk = 1.4, 1.2‐1.6) but not CDH. When the mother had CDH, risk of CDH in the children was increased by almost 13‐fold, but the risk of infrequent headaches was not increased. In multivariate models, headaches in the children were independently predicted by headaches in the mother (P < .001); headache frequency in the children was also predicted by frequency in the mother (P < .001).Conclusions.— Frequency of headaches in children is influenced by frequency of headaches in the mother and seems to aggregate in families. Future studies should focus on the determinants of headache aggregation, including genetic and non‐genetic factors.
The Renin–Angiotensin System Mediates the Effects of Stretch on Conduction Velocity, Connexin43 Expression, and Redistribution in Intact Ventricle
Authors: HUSSAIN WAJID , PATEL PRAVINA M. , CHOWDHURY RASHEDA A. , CABO CANDIDO , CIACCIO EDWARD J. , LAB MAX J. , DUFFY HEATHER S. , WIT ANDREW L. , PETERS NICHOLAS S. 
Published: May 2010

Effect of Stretch on Conduction and Cx43. Introduction: In disease states such as heart failure, myocardial infarction, and hypertrophy, changes in the expression and location of Connexin43 (Cx43) occur (Cx43 remodeling), and may predispose to arrhythmias. Stretch may be an important stimulus to Cx43 remodeling; however, it has only been investigated in neonatal cell cultures, which have different physiological properties than adult myocytes. We hypothesized that localized stretch in vivo causes Cx43 remodeling, with associated changes in conduction, mediated by the renin–angiotensin system (RAS). Methods and Results: In an open‐chest canine model, a device was used to stretch part of the right ventricle (RV) by 22% for 6 hours. Activation mapping using a 312‐electrode array was performed before and after stretch. Regional stretch did not change longitudinal conduction velocity (post‐stretch vs baseline: 51.5 ± 5.2 vs 55.3 ± 8.1 cm/s, P = 0.24, n = 11), but significantly reduced transverse conduction velocity (28.7 ± 2.5 vs 35.4 ± 5.4 cm/s, P < 0.01). It also reduced total Cx43 expression, by Western blotting, compared with nonstretched RV of the same animal (86.1 ± 32.2 vs 100 ± 19.4%, P < 0.02, n = 11). Cx43 labeling redistributed to the lateral cell borders. Stretch caused a small but significant increase in the proportion of the dephosphorylated form of Cx43 (stretch 9.95 ± 1.4% vs control 8.74 ± 1.2%, P < 0.05). Olmesartan, an angiotensin II blocker, prevented the stretch‐induced changes in Cx43 levels, localization, and conduction. Conclusion: Myocardial stretch in vivo has opposite effects to that in neonatal myocytes in vitro. Stretch in vivo causes conduction changes associated with Cx43 remodeling that are likely caused by local stretch‐induced activation of the RAS. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1276‐1283, November 2010)
Periods of Highly Synchronous, Non‐Reentrant Endocardial Activation Cycles Occur During Long‐Duration Ventricular Fibrillation
Authors: ROBICHAUX ROBERT P. , DOSDALL DEREK J. , OSORIO JOSE , GARNER NICHOLAS W. , LI LI , HUANG JIAN , IDEKER RAYMOND E. 
Published: May 2010

Periods of Highly Organized Activation During VF Background: Little is known about long‐duration ventricular fibrillation (LDVF), lasting 1–10 minutes when resuscitation is still possible. Methods and Results: To determine global left ventricle (LV) endocardial activation during LDVF, 6 canines (9.5 ± 0.8 kg) received a 64‐electrode basket catheter in the LV, a right ventricular (RV) catheter, and a 12‐lead electrocardiogram (ECG). Activation sequences of 15 successive cycles after initiation and after 1, 2, 3, 5, 7, and 10 minutes of LDVF were determined. Early during VF, LV endocardial activation was complex and present throughout most (78.0 ± 9.7%) of each cycle consistent with reentry. After 3–7 minutes of LDVF in 5 animals, endocardial activation became highly synchronized and present for only a small percentage of each cycle (18.2 ± 7.7%), indicating that LV endocardial reentry was no longer present. During this synchronization, activations arose focally in Purkinje fibers and spread as large wavefronts to excite the Purkinje system followed by the subendocardial working myocardium. During this synchronization, the ECG continued to appear irregular, consistent with VF, and LV cycle length (183 ± 29 ms) was significantly different than RV cycle length (144 ± 14 ms) and significantly different than the LV cycle length when synchronization was not present (130 ± 11 ms). Conclusion: After 3–7 minutes of LDVF, a highly organized, synchronous, focal LV endocardial activation pattern frequently occurs that is not consistent with reentry but is consistent with triggered activity or abnormal automaticity in Purkinje fibers. The ECG continues to appear irregular during this period, partially because of differences in LV and RV cycle lengths. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1266‐1273, November 2010)
A discrete‐time hazard analysis of the exit of burley tobacco growers in Tennessee, North Carolina, and Virginia
Authors: Tiller Kelly J. , Feleke Shiferaw T. , Starnes Jane H. 
Published: May 2010

AbstractThis article examines the exit and survival dynamics of burley tobacco growers in Tennessee, North Carolina, and Virginia using a discrete‐time hazard logit model. The study also predicts the effects of selected farm and family characteristics on exit hazards, assesses the proportionality of their effects over time and their relative importance in explaining the variation in exit hazards among burley tobacco growers. Results provide the longitudinal progression of the probability of exiting the tobacco industry since the end of the federal tobacco program in 2004, and identify off‐farm participation, percentage of farm receipts from tobacco, tobacco price, educational level, and farm size as the most important determinants of the decision to exit the tobacco industry. Further, the effects of off‐farm participation and farm size on the exit hazards of burley tobacco farms are proportional over time while the effects of the percentage of farm receipts from tobacco and tobacco price are time variant.
Buyers’ perceptions of importance and willingness‐to‐pay for certain attributes of source and production verified bred heifers
Authors: Parcell Joe L. , Franken Jason R.V. , Cox Maria , Patterson David J. , Randle Richard F. 
Published: May 2010

AbstractThis research reports buyers’ perceptions of and willingness‐to‐pay for replacement heifers produced through a rigorous, third‐party verified production protocol. Survey respondents attended and registered to purchase heifers at sanctioned Missouri Show‐Me‐Select Replacement Heifer Program®sales between 1997 and 2002. Responses indicate that pen uniformity, artificially inseminated to calving ease bull, synchronized calving, and heifer size are perceived as important, and their willingness‐to‐pay for these characteristics is economically significant. Though prior research suggests willingness‐to‐pay estimates particularly for inexperienced consumers may be biased, we find little difference between inexperienced and experienced buyers and also little difference from hedonic estimates of heifer characteristics’ value.
Managing increasing environmental risks through agrobiodiversity and agrienvironmental policies
Authors: Baumgärtner Stefan , Quaas Martin F. 
Published: May 2010

AbstractAgrobiodiversity can provide natural insurance to risk‐averse farmers by reducing the variance of crop yield, and to society at large by reducing the uncertainty in the provision of public‐good ecosystem services, for example, CO2storage. We analyze the choice of agrobiodiversity by risk‐averse farmers who have access to financial insurance, and study the implications for agrienvironmental policy design when on‐farm agrobiodiversity generates a positive risk externality. While increasing environmental risk leads private farmers to increase their level of on‐farm agrobiodiversity, the level of agrobiodiversity in the laissez‐faire equilibrium remains inefficiently low. We show how either one of the two agrienvironmental policy instruments can cure this risk‐related market failure: an ex ante Pigouvian subsidy on on‐farm agrobiodiversity and an ex post payment‐by‐result for the actual provision of public environmental benefits. In the absence of regulation, welfare may increase rather than decrease with increasing environmental risk, if the agroecosystem is characterized by a high natural insurance function, low costs, and large external benefits of agrobiodiversity.
Effects of machinery‐sharing arrangements on farm efficiency: evidence from Sweden
Authors: Larsén Karin 
Published: May 2010

AbstractThe effects of partnerships, in the form of machinery‐sharing arrangements, on farm efficiency are analyzed using data for Swedish crop and livestock farms. Efficiency scores are obtained using Data Envelopment Analysis and the findings suggest that efficiency is, on average, higher among partnership farms compared to nonpartnership farms. Moreover, partnership farms that are characterized by the most extensive form of collaboration, that is, that share all machinery with one or several other farms, display the highest average efficiency. In a two‐stage procedure in which efficiency determinants are analyzed in the second stage, the bootstrap procedures suggested by Simar and Wilson (2007) are applied in addition to the conventionally used Tobit regression. Participation in partnership arrangements is found to have a positive and statistically significant impact on farm efficiency.
Influence of bony defects on implant stability
Authors: Merheb Joe , Coucke Wim , Jacobs Reinhilde , Naert Ignace , Quirynen Marc 
Published: May 2010

AbstractIntroduction: The purpose of this study was to analyze the evolution of implant mechanical stability in different types/sizes of bony defects using both Periotest and Osstell devices as “objective tools.”Materials and methods: Thirty‐two implants were randomly allocated to one of the four types of bone defects: marginal bone loss, peri‐apical bone defect, constant width dehiscence and constant length dehiscences. Periotest/Osstell measurements were completed before and during staged bone removal (to enlarge defect size).Results: Significant differences (P<0.05) with initial values were found after a 2 mm marginal bone removal (Osstell/Periotest); for a peri‐apical bone lesion, after removal of 5 mm (Osstell) or 8 mm (Periotest); for a 6‐mm‐long dehiscence, after removal up to 180° of the implant perimeter (Osstell/Periotest); for a 3‐mm‐wide dehiscence, after removal of 10 mm (Osstell) or 6 mm (Periotest).Conclusion: Periotest and Osstell are in general not very sensitive in the identification of peri‐implant bone destruction, except for marginal bone loss. To cite this article:
Merheb J, Coucke W, Jacobs R, Naert I, Quirynen M. Influence of bony defects on implant stability. Clin. Oral Impl. Res. 21, 2010; 919–923. doi: 10.1111/j.1600‐0501.2010.01932.x
Lateral ridge augmentation using equine‐ and bovine‐derived cancellous bone blocks: a feasibility study in dogs
Authors: Schwarz Frank , Ferrari Daniel , Balic Ela , Buser Daniel , Becker Jürgen , Sager Martin 
Published: May 2010

AbstractObjectives: The aim of the present study was to histologically evaluate and compare a new prototype collagen type I/III‐containing equine‐ (EB) and a bovine‐ (BB) derived cancellous bone block in a dog model.Materials and methods: Four standardized box‐shaped defects were bilaterally created at the buccal aspect of the alveolar ridge in the lower jaws of five beagle dogs and randomly allocated to either EB or BB. Each experimental site was covered by a native (non‐crosslinked) collagen membrane and left to heal in a submerged position for 12 weeks. Dissected blocks were processed for semi‐/and quantitative analyses.Results: Both groups had no adverse clinical or histopathological events (i.e. inflammatory/foreign body reactions). BB specimens revealed no signs of biodegradation and were commonly embedded in a fibrous connective tissue. New bone formation and bony graft integration were minimal. In contrast, EB specimens were characterized by a significantly increased cell (i.e. osteoclasts and multinucleated giant cells)‐mediated degradation of the graft material (P<0.001). The amount and extent of bone ingrowth was consistently higher in all EB specimens, but failed to reach statistical significance in comparison with the BB group (P>0.05).Conclusions: It was concluded that the application of EB may not be associated with an improved bone formation than BB. To cite this article:
Schwarz F, Ferrari D, Balic E, Buser D, Becker J, Sager M. Lateral ridge augmentation using equine‐ and bovine‐derived cancellous bone blocks: a feasibility study in dogs. Clin. Oral Impl. Res. 21, 2010; 904–912. doi: 10.1111/j.1600‐0501.2010.01951.x