bluuebunny/crossref_metadata_2025_split huggingface dataset:
mtDNA Lineages Reveal Coronary Artery Disease‐Associated Structures in the Lebanese Population
Authors: Haber Marc , Youhanna Sonia C. , Balanovsky Oleg , Saade Stephanie , Martínez‐Cruz Begoña , Ghassibe‐Sabbagh Michella , Shasha Nabil , Osman Raed , el Bayeh Hamid , Koshel Sergey , Zaporozhchenko Valery , Balanovska Elena , Soria‐Hernanz David F. , Platt Daniel E. , Zalloua Pierre A. 
Published: October 2011

SummaryPopulation origins and ancestry have previously been found to be important determinants of coronary artery disease (CAD). This study investigates associations of Lebanese mitochondrial DNA lineages with CAD and studies their correlation with other populations, exploring population structures that may infer mitochondria functional associations and reveal population movements and origins. Sequencing the mitochondrial hypervariable sequence 1 (HVS‐1) of 363 controls and 448 cases revealed that haplogroup W was more frequent (P= 0.013) in cases compared to controls, and was associated with increased risk of CAD (OR = 5.50, 95% CI = 1.50–35.30, P= 0.026) among Lebanese samples. Haplogroup A was only found in controls (P= 0.029). We have detected stronger geographic correlation between haplogroup W and CAD (Pearson's r= 0.316, P < 0.001) than between haplogroup A and CAD (r= 0.149, P < 0.001). HVS‐1 phylogenetic network of haplogroup W shows controls are restricted to European clusters while cases belong mostly to Middle Eastern natives. The network of haplogroup A shows that the controls belong to a cluster dominated by Central Asians. Our results show evidence of a gene flow into Lebanon, creating CAD‐associated population structures that are similar to those in the source populations, maintained by limited admixture, and probably encompassing variations on the nuclear and/or the mitochondrial genome that are correlated with the disease.
The biodiversity and evolution of lactic flora during ripening of the Iranian semisoft Lighvan cheese
Authors: EDALATIAN MOHAMMAD R , HABIBI NAJAFI MOHAMMAD B , MORTAZAVI ALI , MAYO BALTASAR 
Published: October 2011

Ninety‐five isolated strains of Lactic acid bacteria (LAB) were identified from Lighvan cheese. The LAB evolution showed the dominance of lactococci and lactobacilli in the first stage and substitution of these genera by enterococci at the end of ripening. The most predominant strains were Enterococcus faecium (22.44%), Lactococcus lactis ssp. lactis (20.4%), Lactobacillus plantarum (18.36%) and E. faecalis (14.28%), respectively. Eleven and 51 different carbohydrate fermentation profiles were observed according to API 20 STREP and API 50 CH, respectively. API 20 STREP dendogram showed identical fermentation profiles of some E. faecalis and E. faecium strains, indicating that these strains might be well adapted to the whole cheese manufacture.
Systematic (complete) para‐aortic lymphadenectomy: description of a novel surgical classification with technical and anatomical considerations
Authors: Pomel C , Naik R , Martinez A , Ferron G , Nassif J , Dauplat J , Jeyarajah A 
Published: October 2011

Please cite this paper as: Pomel C, Naik R, Martinez A, Ferron G, Nassif J, Dauplat J, Jeyarajah A. Systematic (complete) para‐aortic lymphadenectomy: description of a novel surgical classification with technical and anatomical considerations. BJOG 2012;119:249–253.The clinical indications for a complete para‐aortic lymphadenectomy in the surgical management of gynaecological malignancies remain controversial. The debate on complete para‐aortic node dissection is hindered by the absence of an identifiable and accepted definition for the procedure of systematic (complete) para‐aortic node dissection. In this paper we propose a classification of para‐aortic lymphadenectomy. We have identified and imaged the most common and rare para‐aortic vascular anomalies that we have encountered. An understanding of the anatomical anomalies in this area also provides a useful reference for the surgical technique that is adopted in order to ensure the completeness of excision.
Maternal mortality attributable to vascular dissection and rupture in the Netherlands: a nationwide confidential enquiry
Authors: la Chapelle CF , Schutte JM , Schuitemaker NWE , Steegers EAP , van Roosmalen J ,   on behalf of the Dutch Maternal Mortality Committee
Published: October 2011

Please cite this paper as: la Chapelle C, Schutte J, Schuitemaker N, Steegers E, van Roosmalen J on behalf of the Dutch Maternal Mortality Commitee. Maternal mortality attributable to vascular dissection and rupture in the Netherlands: a nationwide confidential enquiry. BJOG 2012;119:86–93.Objective  To determine the incidence of maternal deaths attributable to vascular dissection and rupture in the Netherlands, and to assess clinical features, risk factors and the frequency of substandard care in the cases identified.Design  Confidential enquiry into the causes of maternal deaths.Setting  Nationwide in the Netherlands.Population  A total of 3,108,235 live births.Methods  Data analysis of all cases of maternal death from vascular dissection and rupture in the period 1993–2008. A literature review was also performed.Main outcome measures  Incidence, clinical features, risk factors and frequency of substandard care.Results  A total of 23 maternal deaths attributable to vascular dissection and rupture were reported. In most cases the location was aortic (n = 13), followed by coronary (n = 4) and splenic (n = 3) arteries. Clinical features were various, but most women presented with sudden unexplainable pain. Risk factors were present in 14 cases (61%), with hypertension being most frequently reported in ten cases (43%). Substandard care was determined to have been received in 13 cases (56%), inadequate assessment of complaints and a delay in diagnosis being the most frequent problems identified.Conclusions  Vascular dissection and rupture in pregnancy, although rare, carry a high risk of maternal and fetal morbidity and mortality. Because of the rarity of this condition and its variety in presentation, diagnosis is easily missed. A high index of suspicion when a woman presents with suggestive complaints, leading to an early diagnosis, may improve the prognosis for the woman and her child.
Exogenous seeding of cerebral β‐amyloid deposition in βAPP‐transgenic rats
Authors: Rosen Rebecca F. , Fritz Jason J. , Dooyema Jeromy , Cintron Amarallys F. , Hamaguchi Tsuyoshi , Lah James J. , LeVine Harry , Jucker Mathias , Walker Lary C. 
Published: October 2011

J. Neurochem. (2012) 120, 660–666.AbstractDeposition of the amyloid‐β (Aβ) peptide in senile plaques and cerebral Aβ angiopathy (CAA) can be stimulated in Aβ‐precursor protein (APP)‐transgenic mice by the intracerebral injection of dilute brain extracts containing aggregated Aβ seeds. Growing evidence implicates a prion‐like mechanism of corruptive protein templating in this phenomenon, in which aggregated Aβ itself is the seed. Unlike prion disease, which can be induced de novo in animals that are unlikely to spontaneously develop the disease, previous experiments with Aβ seeding have employed animal models that, as they age, eventually will generate Aβ lesions in the absence of seeding. In the present study, we first established that a transgenic rat model expressing human APP (APP21 line) does not manifest endogenous deposits of Aβ within the course of its median lifespan (30 months). Next, we injected 3‐month‐old APP21 rats intrahippocampally with dilute Alzheimer brain extracts containing aggregated Aβ. After a 9‐month incubation period, these rats had developed senile plaques and CAA in the injected hippocampus, whereas control rats remained free of such lesions. These findings underscore the co‐dependence of agent and host in governing seeded protein aggregation, and show that cerebral Aβ‐amyloidosis can be induced even in animals that are relatively refractory to the spontaneous origination of parenchymal and vascular deposits of Aβ.
Nitrous oxide emissions from vegetables grown in a polytunnel treated with high rates of applied nitrogen fertilizers in Southern China
Authors: Min J. , Shi W. , Xing G. , Powlson D. , Zhu Z. 
Published: October 2011

AbstractSoils under intensive agricultural practices such as those for growing vegetables in plastic greenhouses are an important anthropogenic source of nitrous oxide (N2O). Nitrous oxide emissions and measures to mitigate them through fertilizer N management have been less frequently studied than open field systems. The objectives of this study were to measure N2O emissions from vegetables under greenhouse conditions in Southern China and to investigate the effect of reducing the amount of applied synthetic N fertilizer compared with local practice. Results indicate that the average N2O‐N flux during the growth of four vegetables (tomato, cucumber, celery and a second tomato crop) was 117.4 ± 9 μg N/m2/h, and the annual emission rate was 8.1 ± 0.6 kg/N/ha for local farms. Temperature was important with much lower emissions during the celery‐growing season when soil and air temperatures were frequently <10 °C. Nitrous oxide emissions from the greenhouse vegetables were seven times greater than from the rice–wheat system in the same area and soils. Reducing the amount of applied synthetic N fertilizer by 40% relative to local farmers’ normal usage could reduce annual cumulative N2O emissions by 33% without any impact on crop yields.
Mechanism of action of a nanomolar potent, allosteric antagonist of the thyroid‐stimulating hormone receptor
Authors: van Koppen Chris J , de Gooyer Marcel E , Karstens Willem‐Jan , Plate Ralf , Conti Paolo GM , van Achterberg Tanja AE , van Amstel Monique GA , Brands Jolanda HGM , Wat Jesse , Berg Rob JW , Lane J Robert D , Miltenburg Andre MM , Timmers C Marco 
Published: October 2011

BACKGROUND AND PURPOSE Graves' disease (GD) is an autoimmune disease in which the thyroid is overactive, producing excessive amounts of thyroid hormones, caused by thyroid‐stimulating hormone (TSH) receptor‐stimulating immunoglobulins (TSIs). Many GD patients also suffer from thyroid eye disease (Graves' ophthalmopathy or GO), as TSIs also activate TSH receptors in orbital tissue. We recently developed low molecular weight (LMW) TSH receptor antagonists as a novel therapeutic strategy for the treatment of GD and GO. Here, we determined the molecular pharmacology of a prototypic, nanomolar potent LMW TSH receptor antagonist, Org 274179‐0.EXPERIMENTAL APPROACH Using CHO cells heterogeneously expressing human TSH receptors and rat FRTL‐5 cells endogenously expressing rat TSH receptors, we determined the potency and efficacy of Org 274179‐0 at antagonizing TSH‐ and TSI‐induced TSH receptor signalling and its cross‐reactivity at related follicle‐stimulating hormone and luteinizing hormone receptors. We analysed the allosteric mode of interaction of Org 274179‐0 and determined whether it is an inverse agonist at five naturally occurring, constitutively active TSH receptor mutants.KEY RESULTS Nanomolar concentrations of Org 274179‐0 completely inhibited TSH (and TSI)‐mediated TSH receptor activation with little effect on the potency of TSH, in accordance with an allosteric mechanism of action. Conversely, increasing levels of TSH receptor stimulation only marginally reduced the antagonist potency of Org 274179‐0. Org 274179‐0 fully blocked the increased basal activity of all the constitutively active TSH receptor mutants tested with nanomolar potencies.CONCLUSIONS AND IMPLICATIONS Nanomolar potent TSH receptor antagonists like Org 274179‐0 have therapeutic potential for the treatment of GD and GO.
Transient receptor potential melastatin 4 inhibitor 9‐phenanthrol abolishes arrhythmias induced by hypoxia and re‐oxygenation in mouse ventricle
Authors: Simard Christophe , Sallé Laurent , Rouet René , Guinamard Romain 
Published: October 2011

BACKGROUND AND PURPOSE Hypoxia and subsequent re‐oxygenation are associated with cardiac arrhythmias such as early afterdepolarizations (EADs), which may be partly explained by perturbations in cytosolic calcium concentration. Transient receptor potential melastatin 4 (TRPM4), a calcium‐activated non‐selective cation channel, is functionally expressed in the heart. Based on its biophysical properties, it is likely to participate in EADs. Hence, modulators of TRPM4 activity may influence arrhythmias. The aim of this study was to investigate the possible anti‐arrhythmic effect of 9‐phenanthrol, a TRPM4 inhibitor in a murine heart model of hypoxia and re‐oxygenation‐induced EADs.EXPERIMENTAL APPROACH Mouse heart was removed, and the right ventricle was pinned in a superfusion chamber. After a period of normoxia, the preparation was superfused for 2 h with a hypoxic solution and then re‐oxygenated. Spontaneous electrical activity was investigated by intracellular microelectrode recordings.KEY RESULTS In normoxic conditions, the ventricle exhibited spontaneous action potentials. Application of the hypoxia and re‐oxygenation protocol unmasked hypoxia‐induced EADs, the occurrence of which increased under re‐oxygenation. The frequency of these EADs was reduced by superfusion with either flufenamic acid, a blocker of Ca2+‐dependent cation channels or with 9‐phenanthrol. Superfusion with 9‐phenanthrol (10−5 or 10−4 mol·L−1) caused a dramatic dose‐dependent abolition of EADs.CONCLUSIONS AND IMPLICATIONS Hypoxia and re‐oxygenation‐induced EADs can be generated in the mouse heart model. 9‐Phenanthrol abolished EADs, which strongly suggests the involvement of TRPM4 in the generation of EAD. This identifies non‐selective cation channels inhibitors as new pharmacological candidates in the treatment of arrhythmias.
Chronic mTOR inhibition by rapamycin induces muscle insulin resistance despite weight loss in rats
Authors: Deblon N , Bourgoin L , Veyrat‐Durebex C , Peyrou M , Vinciguerra M , Caillon A , Maeder C , Fournier M , Montet X , Rohner‐Jeanrenaud F , Foti M 
Published: October 2011

BACKGROUND AND PURPOSE mTOR inhibitors are currently used as immunosuppressants in transplanted patients and as promising anti‐cancer agents. However, new‐onset diabetes is a frequent complication occurring in patients treated with mTOR inhibitors such as rapamycin (Sirolimus). Here, we investigated the mechanisms associated with the diabetogenic effects of chronic Sirolimus administration in rats and in in vitro cell cultures.EXPERIMENTAL APPROACH Sirolimus was administered to rats fed either a standard or high‐fat diet for 21 days. Metabolic parameters were measured in vivo and in ex vivo tissues. Insulin sensitivity was assessed by glucose tolerance tests and euglycaemic hyperinsulinaemic clamps. Rapamycin effects on glucose metabolism and insulin signalling were further evaluated in cultured myotubes.KEY RESULTS Sirolimus induced a decrease in food intake and concomitant weight loss. It also induced specific fat mass loss that was independent of changes in food intake. Despite these beneficial effects, Sirolimus‐treated rats were glucose intolerant, hyperinsulinaemic and hyperglycaemic, but not hyperlipidaemic. The euglycaemic hyperinsulinaemic clamp measurements showed skeletal muscle is a major site of Sirolimus‐induced insulin resistance. At the molecular level, long‐term Sirolimus administration attenuated glucose uptake and metabolism in skeletal muscle by preventing full insulin‐induced Akt activation and altering the expression and translocation of glucose transporters to the plasma membrane. In rats fed a high‐fat diet, these metabolic defects were exacerbated, although Sirolimus‐treated animals were protected from diet‐induced obesity.CONCLUSIONS AND IMPLICATIONS Taken together, our data demonstrate that the diabetogenic effect of chronic rapamycin administration is due to an impaired insulin action on glucose metabolism in skeletal muscles.
Differential signalling in human cannabinoid CB1 receptors and their splice variants in autaptic hippocampal neurones
Authors: Straiker Alex , Wager‐Miller Jim , Hutchens Jacqueline , Mackie Ken 
Published: October 2011

BACKGROUND AND PURPOSE Cannabinoids such as Δ9‐ tetrahydrocannabinol, the major psychoactive component of marijuana and hashish, primarily act via cannabinoid CB1 and CB2 receptors to produce characteristic behavioural effects in humans. Due to the tractability of rodent models for electrophysiological and behavioural studies, most of the studies of cannabinoid receptor action have used rodent cannabinoid receptors. While CB1 receptors are relatively well‐conserved among mammals, human CB1 (hCB1) differs from rCB1 and mCB1 receptors at 13 residues, which may result in differential signalling. In addition, two hCB1 splice variants (hCB1a and hCB1b) have been reported, diverging in their amino‐termini relative to hCB1 receptors. In this study, we have examined hCB1 signalling in neurones.EXPERIMENTAL APPROACH hCB1, hCB1a hCB1b or rCB1 receptors were expressed in autaptic cultured hippocampal neurones from CB1−/− mice. Such cells express a complete endogenous cannabinoid signalling system. Electrophysiological techniques were used to assess CB1 receptor‐mediated signalling.KEY RESULTS Expressed in autaptic hippocampal neurones cultured from CB1−/− mice, hCB1, hCB1a and hCB1b signal differentially from one another and from rodent CB1 receptors. Specifically, hCB1 receptors inhibit synaptic transmission less effectively than rCB1 receptors.CONCLUSIONS AND IMPLICATIONS Our results suggest that cannabinoid receptor signalling in humans is quantitatively very different from that in rodents. As the problems of marijuana and hashish abuse occur in humans, our results highlight the importance of studying hCB1 receptors. They also suggest further study of the distribution and function of hCB1 receptor splice variants, given their differential signalling and potential impact on human health.LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue‐8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue‐7
Making Creative Spaces: The Art and Design Classroom as a Site of Performativity
Authors: Wild Carol 
Published: October 2011

AbstractRather than taking a transformational role in schools, new art and design teachers quickly become subject to ‘school art’ orthodoxy. Theories of subjectivity and the development of professional identity within communities of practice can feel far removed from the classroom. This article seeks to make clearer the processes by which teacher identity and practice becomes normalised and proposes ways that such processes may be resisted. With reference to Foucault, Lyotard, Bruner, Wenger and Bey, the classroom as a site of performativity is contrasted with alternative heterotopia‐like sites away from the spectre of observation, where different identities and behaviours can be explored. These temporary sites of difference are an antidote to the orthodoxy of the ‘school art’ condition and open up the possibility for teachers, both new and experienced, to implement a more hospitable, participatory pedagogy.
Deregulation of Hippo kinase signalling in Human hepatic malignancies
Authors: Li Hua , Wolfe Andy , Septer Seth , Edwards Genea , Zhong Xiaobo , Bashar Abdulkarim Ahmad , Ranganathan Sarangarajan , Apte Udayan 
Published: October 2011

AbstractBackground/AimsHepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and hepatoblastoma (HB) are the main hepatic malignancies with limited treatment options and high mortality. Recent studies have implicated Hippo kinase pathway in cancer development, but detailed analysis of Hippo kinase signalling in human hepatic malignancies, especially CC and HB, is lacking.MethodsWe investigated Hippo kinase signalling in HCC, CC and HB using cells and patient samples.ResultsIncreased expression of yes‐associated protein (Yap), the downstream effector of the Hippo kinase pathway, was observed in HCC cells, and siRNA‐mediated knockdown of Yap resulted in decreased survival of HCC cells. The density‐dependent activation of Hippo kinase pathway characteristic of normal cells was not observed in HCC cells and CCLP cells, a cholangiocarcinoma cell line. Immunohistochemistry of Yap in HCC, CC and HB tissues indicated extensive nuclear localization of Yap in majority of tissues. Western blot analysis performed using total cell extracts from patient samples and normal livers showed extensive activation of Yap. Marked induction of Glypican‐3, CTGF and Survivin, the three Yap target genes was observed in the tumour samples. Further analysis revealed significant decrease in expression and activity of Lats kinase, the main upstream regulator of Yap. However, no change in activation of Mst‐2 kinase, the upstream regulator of Lats kinase was observed.ConclusionsThese data show that Yap induction mediated by inactivation of Lats is observed in hepatic malignancies. These studies highlight Hippo kinase pathway as a novel therapeutic target for hepatic malignancies.
Children with Heavy Prenatal Alcohol Exposure Exhibit Deficits when Regulating Isometric Force
Authors: Simmons Roger W. , Nguyen Tanya T. , Levy Susan S. , Thomas Jennifer D. , Mattson Sarah N. , Riley Edward P. 
Published: October 2011

Background:  Production of isometric (i.e., constant) force is an essential component of performing everyday functional tasks, yet no studies have investigated how this type of force is regulated in children with confirmed histories of heavy prenatal alcohol exposure.
Methods:  Children 7 to 17 years old with heavy prenatal alcohol exposure (n = 25) and without exposure (n = 18) applied force to a load cell to generate an isometric force that matched a criterion target force displayed on a computer monitor. Two levels of target force were investigated in combination with 3 levels of visual feedback frequency that appeared on the computer monitor as a series of yellow dots. Force was maintained for 20 seconds and participants completed 6 trials per test condition.
Results:  Root‐mean‐square error, signal‐to‐noise ratio, and sample entropy indexed response accuracy, response variability, and signal complexity, respectively. The analyses revealed that in comparison with controls, children with gestational ethanol exposure were significantly less accurate and more variable in regulating their force output and generated a response signal with greater regularity and less complexity in the time domain.
Conclusions:  Children with prenatal alcohol exposure experience significant deficits in isometric force production that may impede their ability to perform basic motor skills and activities in everyday tasks.