2,241 research outputs found
The proinflammatory cytokine Interleukin-1 beta does not modify lesion evolution in an endothelin-induced model of focal cerebral ischaemia in the rat
No full textRainbow Valley as embodied heaven: L.M. Montgomery’s narrative spirituality in Rainbow Valley
No full textIntriguingly, L.M. Montgomery’s generally realistic fiction is filled with fantastic elements. This article argues that by following Montgomery into the heavenly fairyland of Rainbow Valley, readers can discern a joyful, creative, imaginative, and integrated image of spiritual life in the conversations, the characters, and the magic valley itself
Befriending the darkness: L.M. Montgomery’s lived theodicy in Anne’s House of Dreams
No full textIn Anne’s House of Dreams, which Elizabeth Epperly calls Montgomery’s most philosophical novel, Montgomery delves into painful topics of loss, suicide, bad marriages, ill-timed love, poverty, and the beautiful-terrible consequences of duty. The result is a complex and nuanced consideration of faithful living in the face of unexplainable evil that functions as a lived theodicy in story form.
“I reckon when the darkness is close to us it is a friend. But when we sorter push it away from us—divorce ourselves from it, so to speak, with lantern light—it becomes an enemy.”
—L.M. Montgomery, Captain Jim in Anne’s House of Dream
MCP-1 and murine prion disease: separation of early behavioural dysfunction from overt clinical disease
No full textPrion diseases are chronic, fatal neurodegenerative conditions of the CNS. We have investigated the role of monocyte chemoattractant protein-1 (MCP-1) in the ME7 model of murine prion disease. MCP-1 expression increased in the CNS throughout disease progression and was positively correlated with microglial activation. We subsequently compared the inflammatory response, pathology and behavioural changes in wild-type (wt) mice and MCP-1 knockout mice (MCP-1?/?) inoculated with ME7. Late-stage clinical signs were delayed by 4 weeks in MCP-1?/? mice, and survival time increased by 2–3 weeks. By contrast, early changes in affective behaviours and locomotor activity were not delayed in onset. There was also no difference in microglial activation or neuronal death in the hippocampus and thalamus of wt mice and MCP-1?/? mice. These results highlight an important dissociation between prolonged survival, early behavioural dysfunction and hippocampal/thalamic pathology when considering therapeutic intervention for human prion diseases and other chronic neurodegenerative condition
Brain cytokine synthesis induced by an intraparenchymal injection of LPS is reduced in MCP-1-deficient mice prior to leucocyte recruitment
No full textWe have previously shown that ischaemic lesions are smaller in monocyte chemoattractant protein-1-deficient (MCP-1–/–) mice than in wild-type (wt) controls. In addition to its role as a monocyte chemoattractant, monocyte chemoattractant protein-1 (MCP-1) has been proposed to contribute to lesion progression after focal ischaemia by driving local cytokine synthesis by resident glia. To investigate this hypothesis we injected lipopolysaccharide (LPS) into the brain parenchyma of MCP-1–/– mice and compared the resulting inflammatory response and production of proinflammatory cytokines to those in wt mice. Microglial and astrocyte morphological activation was the same in the two strains, but MCP-1–/– mice showed significantly lower levels of proinflammatory cytokine synthesis; interleukin-1? (IL-1?) and tumour necrosis factor-? (TNF-?) levels were up to 50% lower than in wt controls after 6 h. This reduced synthesis of proinflammatory cytokines occurred well before leucocyte recruitment to the central nervous system (CNS) is observed in this model of acute inflammation and thus cannot be attributed to lower numbers of recruited monocytes at the site of injury. We propose that MCP-1 contributes to acute CNS inflammation by pleiotropic mechanisms. In addition to being a potent chemoattractant for monocytes, we provide evidence here that MCP-1 can modify the responsiveness of CNS glia to acute inflammatory stimuli prior to leucocyte recruitment, thereby acting as a priming stimulus for cytokine synthesis in cells such as microglia.<br/
Sub-pyrogenic systemic inflammation impacts on brain and behavior, independent of cytokines
No full textSystemic inflammation impacts on the brain and gives rise to behavioral changes, often referred to as ‘sickness behavior’. These symptoms are thought to be mainly mediated by pro-inflammatory cytokines. We have investigated the communication pathways between the immune system and brain following sub-pyrogenic inflammation. Low grade systemic inflammation was induced in mice using lipopolysaccharide (LPS); 1–100 ?g/kg to mimic aspects of bacterial infection. Changes in fever, open-field activity, burrowing and consumption of glucose solution were assessed and immune activation was studied in the periphery and brain by measuring cytokine production, and immunohistochemistry to study changes in immune cell phenotype. Sub-pyrogenic inflammation resulted in changes in a species-typical, untrained behavior (burrowing) that depends on the integrity of the hippocampus. Increased expression of cytokines was observed in the periphery and selected regions of the brain which coincided with changes in behavior. However, peripheral neutralization of LPS-induced pro-inflammatory cytokines IL-1?, IL-6 and TNF-? did not abrogate the LPS-induced behavioral changes nor affect CNS cytokine synthesis. In contrast, pretreatment of mice with indomethacin completely prevented LPS-induced behavior changes, without affecting cytokine levels. Taken together, these experiments suggest a key role for prostaglandins, rather than cytokines, in communicating to the brain
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India's Vibgyor man ::selected writings and speeches of L.M. Singhvi /
No full textDr L.M. Singhvi had a multifaceted personality - author, jurist, statesman, philosopher and social reformer. A product of many reputed universities like the University of Allahabad, University of Rajasthan, Harvard University and Cornell University, he was the most celebrated Indian public figure of contemporary times. This volume reflects L.M. Singhvi's prodigious scholarship
The role of L.M. Karakhan in the Chinese policy of the Soviet Union (1923–1926)
No full textIn the 1920s, the young Soviet state pursued several, sometimes mutually exclusive, goals in its policy towards China. On the one hand, the Soviet leadership did its best to achieve international recognition and sought to protect its vital interests. On the other hand, it actively promoted the idea of a world revolution. Under those circumstances, the country’s foreign ministry needed experienced, flexible, and pragmatic diplomats. In this regard, the activities of L.M. Karakhan, who was sent as a Soviet emissary to the Republic of China to address these sensitive issues, are of particular interest. The figure of L.M. Karakhan is all the more remarkable because, being one of the architects of the USSR’s foreign policy towards China, he himself has not received much attention in either Soviet or Russian historiography. On the basis of new archival documents and Chinese primary sources the paper attempts to give a comprehensive assessment of L.M. Karakhan’s tenure first as a plenipotentiary and then as an ambassador of the USSR to China. The first sections consider the tasks of L.M. Karakhan’s diplomatic mission in China and the vicissitudes of the negotiations on the Soviet-Chinese agreement on the establishment of diplomatic relations. To that end, the Soviet diplomat, following the directives from Moscow, flexibly maneuvered between various groupings of Chinese elites and resisted the pressure of other great powers’ representatives. The following sections examine L.M. Karakhan’s activities as a Soviet ambassador. The author concludes that L.M. Karakhan consistently defended the national interests of the USSR, skillfully combining a fine diplomatic game and assertiveness, even rigidity at times. The latter was vividly manifested in the most challenging issues of Soviet-Chinese relations, such as disputes over the status of the Chinese Eastern Railway and Outer Mongolia. At the same time, the ambassador took an active part in organizing and supporting the revolutionary movement in China. In fact, L.M. Karakhan served as a central coordinator of the Soviet aid to the Kuomintang, determining both its forms and substance. The author concludes that L.M. Karakhan proved himself not merely as an agent of the Soviet leadership, but also as a politician in its own right capable to effectively address a wide range of tasks, some of which had not originally been intended by his mission. That said it is worth mentioning that the assertive, tough style of the Soviet diplomat often raised a lot of criticism among foreign representatives, since it was at odds with the declared USSR intentions to break with the foreign policy practices of tsarist Russia
Principal Aspects of Olbian History in Works of L.M. Slavin
No full textСтаттю присвячено загальному огляду головних питань з історії Ольвії, які вивчав Л.М. Славін, у контексті
минулих і сучасних досліджень.Научная деятельность Л.М. Славина была всесторонней, однако на первое место он всегда ставил интерпретацию и
хронологию археологических памятников. Вместе с тем ему принадлежит много исторических работ. Самой важной
научно-теоретической разработкой Л.М. Славина была общеисторическая периодизация Ольвии. Л.М. Славин первым
обосновал принципы создания исторической периодизации. Он считал целесообразным разделить историю Ольвии
на ряд периодов, качественно отличающихся друг от друга прежде всего по признакам экономического развития, социально-политической жизни, исторических судеб. Ученый впервые попытался применить комплексную методику
исследования источников для каждого из пяти выделенных им периодов с их подробной характеристикой. В своих
обобщающих работах Л.М. Славин оставил много убедительных выводов и соображений относительно разных вопросов
исторического, экономического и культурного развития Ольвии.Research activity of L.M. Slavin was comprehensive, though his principal aim was the interpretation and chronology
of archaeological monuments. In addition, he was the author of many historical works. The most important theoretical
research development of L.M. Slavin was the general historical periodization of Olbia. L.M. Slavin was the first
who substantiated the principles for historical periodization. He considered that it was expedient to divide the
history of Olbia into several periods first of all on the basis of the evidence of economic development, social and
political life, and historic destinies. Also he tried to apply the comprehensive methodology of monuments research
for each of five distinguished periods and for their detailed description
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