The effects of lysophospholipids and oxidised low-density lipoproteins on the L-arginine: Nitric oxide pathways in isolated rabbit and rat aorta

Elevated plasma levels of low-density lipoproteins (LDL) are a major risk factor for the development of atherosclerosis. Atherosclerotic vessels from humans and animals show impaired endothelium-dependent relaxations (EDR) and altered responses to contractile agonists. Recent evidence suggests that oxidation of LDL is a key process in atherogenesis and plays an important role in the alterations in vascular reactivity. This study investigated the effects of a major component of oxidised LDL (OXLDL), lysophosphatidylcholine (LPC), on vascular responses in isolated rabbit and rat aortic rings. In addition, the effects of OXLDL on EDR in rat aortic rings was also examined. Furthermore, the possibility that impaired EDR in atherosclerotic vessels could be restored by L-arginine was investigated. LPC caused immediate, dose dependent and partially reversible inhibition of EDR evoked by ACh, ATP and A23187 in rabbit aortic rings. This inhibition was decreased by serum albumin but not by L-arginine or indomethacin. Relaxations to exogenous NO and glyceryl trinitrate in endothelium-denuded tissues were unaffected by LPC, but responses were inhibited in endothelium-intact rings suggesting the release of an inhibitory factor from the endothelium. LPC also evokes EDR which are mediated by the release of NO. This dual effect of LPC can be demonstrated in the same tissue. Contractile responses to phenylephrine (PE) and 5-HT were unaffected in denuded tissues, but were inhibited in endothelium-intact tissues, again suggesting the release of a factor from the endothelium. Relaxations evoked by L-arginine in isolated rat aortic rings were mediated by an inducible nitric oxide synthase (NOS). At a concentration that inhibited relaxations elicited by ACh, OXLDL did not influence L-arginine-evoked relaxations, whereas LPC potentiated responses. NOS activity induced in vivo by endotoxin injection, was studied ex vivo by observation of PE-evoked contractions. Contractions were attenuated in rings from endotoxin-treated rats. However, the effect of this treatment was unaffected by the presence of OXLDL or LPC. Aortic rings from WHHL rabbits which spontaneously develop atherosclerosis, showed impaired EDR. This impairment was not influenced by incubation of the tissues with L-arginine. Furthermore, rabbits fed a diet supplemented with L-arginine did not show improved endothelium- dependent responses in vitro. In addition, L-arginine feeding did not influence contractile responses to PE. In conclusion, LPC can modulate EDR and contractile responses in isolated tissues although, these effects do not mimic those reported for OXLDL. In contrast, OXLDL and LPC do not inhibit the activity of an inducible form of NOS. Finally, the impairment of EDR observed in atherosclerotic vessels cannot be reversed by the administration of L-arginine

India: Domestic Issues, Strategic Dynamics, and U.S. Relations

[Excerpt] President Barack Obama’s Administration has sought to build upon the deepened U.S. engagement with India begun by President Bill Clinton in 2000 and expanded upon during much of the past decade under President G.W. Bush. This “U.S.-India 3.0” diplomacy was most recently on display in July 2011, when the second U.S.-India Strategic Dialogue session saw a large delegation of senior U.S. officials visit New Delhi to discuss a broad range of global and bilateral issues. Many analysts view the U.S.-India relationship as being among the world’s most important in coming decades and see potentially large benefits to be accrued through engagement on many convergent interests. Bilateral initiatives are underway in all areas, although independent analysts in both countries worry that the partnership has lost momentum in recent years. Outstanding areas of bilateral friction include obstacles to bilateral trade and investment, including in the high-technology sector; outsourcing; the status of conflict in Afghanistan; climate change; and stalled efforts to initiate civil nuclear cooperation. India is the world’s most populous democracy and remains firmly committed to representative government and rule of law. Its left-leaning Congress Party-led ruling national coalition has been in power for more than seven years under the leadership of Prime Minister Manmohan Singh, an Oxford-trained economist. New Delhi’s engagement with regional and other states is extensive and reflects its rising geopolitical status. The national economy has been growing rapidly—India’s is projected to be the world’s third-largest economy in the foreseeable future—yet poor infrastructure, booming energy demand, and restrictive trade and investment practices are seen to hamper full economic potential. Despite the growth of a large urban middle-class, India’s remains a largely rural and agriculture-based society, and is home to some 500-600 million people living in poverty. This report will be updated periodically

India-U.S. Relations

This report focuses on relations between the United States and India, a relationship deepened in the Clinton and G. W. Bush Administrations. The Obama Administrations seeks to continue developing this relationship. Continuing U.S. interest in South Asia focuses on ongoing tensions between India and Pakistan, the proliferation of nuclear weapons and ballistic missiles, human rights issues, caste-based discrimination, and India's economic expansion

The Identification of the X-ray Counterpart to PSR J2021+4026

We report the probable identification of the X-ray counterpart to the gamma-ray pulsar PSR J2021+4026 using imaging with the Chandra X-ray Observatory ACIS and timing analysis with the Fermi satellite. Given the statistical and systematic errors, the positions determined by both satellites are coincident. The X-ray source position is R.A. 20h21m30.733s, Decl. +40 deg 26 min 46.04sec (J2000) with an estimated uncertainty of 1.3 arsec combined statistical and systematic error. Moreover, both the X-ray to gamma-ray and the X-ray to optical flux ratios are sensible assuming a neutron star origin for the X-ray flux. The X-ray source has no cataloged infrared-to-visible counterpart and, through new observations, we set upper limits to its optical emission of i' >23.0 mag and r' > 25.2mag. The source exhibits an X-ray spectrum with most likely both a powerlaw and a thermal component. We also report on the X-ray and visible light properties of the 43 other sources detected in our Chandra observation.Comment: Accepted for publication in the Astrophysical Journa

2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer

To complement the existing treatment guidelines, ESMO organises consensus conferences to focus on specific issues. The 2nd ESMO Consensus Conference on Lung Cancer included 35 experts who met to address several questions on non-small-cell lung cancer (NSCLC). Recommendations were made with reference to grade of recommendation and level of evidence. This paper focuses on locally advanced diseas

A silent cry for leadership : organizing for leading (in) clusters

Leadership research so far has neglected clusters as a particular context for leadership, while research on networks and clusters has hardly studied leadership issues. This paper fills this dual gap in the abundant research on leadership on the one hand and on networks/clusters on the other by investigating leadership in photonics clusters from a structuration perspective. Apart from giving an insight into the variety and patterns of leadership practices observed, the paper addresses the dilemma that regional innovation systems such as clusters usually have a critical need of some kind of leadership, but that neither individual nor organizational actors wish to be led. This dilemma can only be ‘managed’ by organizing for leading (in) clusters in a certain way

Formation of a cytoplasmic salt bridge network in the matrix state is a fundamental step in the transport mechanism of the mitochondrial ADP/ATP carrier

Mitochondrial ADP/ATP carriers catalyze the equimolar exchange of ADP and ATP across the mitochondrial inner membrane. Structurally, they consist of three homologous domains with a single substrate binding site. They alternate between a cytoplasmic and matrix state in which the binding site is accessible to these compartments for binding of ADP or ATP. It has been proposed that cycling between states occurs by disruption and formation of a matrix and cytoplasmic salt bridge network in an alternating way, but formation of the latter has not been shown experimentally. Here, we show that state-dependent formation of the cytoplasmic salt bridge network can be demonstrated by measuring the effect of mutations on the thermal stability of detergent-solubilized carriers locked in a specific state. For this purpose, mutations were made to increase or decrease the overall interaction energy of the cytoplasmic network. When locked in the cytoplasmic state by the inhibitor carboxyatractyloside, the thermostabilities of the mutant and wild-type carriers were similar, but when locked in the matrix state by the inhibitor bongkrekic acid, they correlated with the predicted interaction energy of the cytoplasmic network, demonstrating its formation. Changing the interaction energy of the cytoplasmic network also had a profound effect on the kinetics of transport, indicating that formation of the network is a key step in the transport cycle. These results are consistent with a unique alternating access mechanism that involves the simultaneous rotation of the three domains around a central translocation pathway

2nd ESMO Consensus Conference on Lung Cancer: early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up

This manuscript provides recommendations for the diagnosis, treatment and follow-up of early stage non-small cell lung cancer developed during the 2nd ESMO Consensus Conference on Lung Cancer in May 201

Towards a framework for critical citizenship education

Increasingly countries around the world are promoting forms of "critical" citizenship in the planned curricula of schools. However, the intended meaning behind this term varies markedly and can range from a set of creative and technical skills under the label "critical thinking" to a desire to encourage engagement, action and political emancipation, often labelled "critical pedagogy". This paper distinguishes these manifestations of the "critical" and, based on an analysis of the prevailing models of critical pedagogy and citizenship education, develops a conceptual framework for analysing and comparing the nature of critical citizenship