Inflammation and Anti-inflammatory strategies for alzheimer disease a mini review

Until recently, the central nervous system (CNS) has been thought to be an immune privileged organ. However, it is now understood that neuroinflammation is linked with the development of several CNS diseases including late-onset Alzheimer's disease (LOAD). The development of inflammation is a complex process involving a wide array of molecular interactions which in the CNS remains to be further characterized. The development of neuroinflammation may represent an important link between the early stages of LOAD and its pathological outcome. It is proposed that risks for LOAD, which include genetic, biological and environmental factors can each contribute to impairment of normal CNS regulation and function. The links between risk factors and the development of neuroinflammation are numerous and involve many complex interactions which contribute to vascular compromise, oxidative stress and ultimately neuroinflammation. Once this cascade of events is initiated, the process of neuroinflammation can become overactivated resulting in further cellular damage and loss of neuronal function. Additionally, neuroinflammation has been associated with the formation of amyloid plaques and neurofibrillary tangles, the pathological hallmarks of LOAD. Increased levels of inflammatory markers have been correlated with an advanced cognitive impairment. Based on this knowledge, new therapies aimed at limiting onset of neuroinflammation could arrest or even reverse the development of the disease.

The Israeli-Palestinian Conflict: A People's War

The conflict between Israelis and Palestinians is one of the most enduring and complex in the modern world. But, why did the conflict break out? Who is demanding what, and why is peace so difficult to achieve?

The Israeli-Palestinian Conflict tackles the subject and analyses the conflict from its historical roots in the late nineteenth century to the present attempts at conflict resolution in the twenty-first century.

Framing the debate and analysis around issues such as Zionism, Palestinian nationalism, international peace efforts, the refugees, state-building, democracy and religious opposition and highlighted by first hand quotes and sources of the conflict from its major participants, Beverley Milton-Edwards explores the deep impact of the conflict on regional politics in the Middle East and why the enmity between Palestinians and Israelis has become a number one global issue drawing in the world’s most important global actors.

An essential insight into the complexities of one of the world’s most enduring conflicts between Israelis and Palestinians, this textbook is designed to make a complex subject accessible to all. Key features include a chronology of events and annotated further reading at the end of each chapter.

The Israeli-Palestinian Conflict is an ideal and authoritative introduction into aspects of politics in Israel, among the Palestinians – a vitally important issue for those studying the politics of the Middle East.

Antibody Targeting of Cathepsin S Inhibits Angiogenesis and Synergistically Enhances Anti-VEGF

BACKGROUND: Angiogenesis is a key hallmark of tumourigenesis and its inhibition is a proven strategy for the development of novel anti-cancer therapeutics. An important aspect of early angiogenesis is the co-ordinated migration and invasion of endothelial cells through the hypoxic tumour tissue. Cathepsin S has been shown to play an important role in angiogenesis as has vascular endothelial growth factor (VEGF). We sought to assess the anti-angiogenic effect of Fsn0503, a novel cathepsin S inhibitory antibody, when combined with anti-VEGF on vascular development.

METHODOLOGY/PRINCIPAL FINDINGS: Cathepsin S expression and secretion from endothelial cells was characterised using RT-PCR and western blotting. We further show that cathepsin S promotes pericellular hydrolysis of extracellular matrix components in the tumour microenvironment and facilitates endothelial invasion. The cathepsin S inhibitory antibody, Fsn0503, blocks extracellular proteolysis, inhibiting endothelial invasion and tube formation in cell-based assays. The anti-angiogenic effects of Fsn0503 were also shown in vivo where it significantly retarded the development of vasculature in human xenograft models. Furthermore, when Fsn0503 was combined with an anti-VEGF antibody, a synergistic inhibition of microvascular development was observed.

CONCLUSIONS/SIGNIFICANCE: Taken together, this data demonstrates that the antibody-mediated targeting of cathepsin S represents a novel method of inhibiting angiogenesis. Furthermore, when used in combination with anti-VEGF therapies, Fsn0503 has the potential to significantly enhance current treatments of tumour neovascularisation and may also be of use in the treatment of other conditions associated with inappropriate angiogenesis.

Cold War Along the Emerald Curtain: Rural Boundaries in a Contested Border Zone

This paper examines how anxieties about ethnic identity proliferate as state borders begin to shift and open in response to accelerating possibilities of cross-border cooperation. As the border becomes more porous, social and cultural boundaries become marked in other ways, spatially re-scaled to reflect new uncertainties consequent upon border change. Using an example from the Irish land border, the paper traces how national space is re-imagined and re-placed in the everyday practices of residents in a violent border zone from which the state is ostensibly retreating. It shows that communal division is as sharply drawn as ever at a time when the ‘visibility’ of the state border itself is beginning to diminish.