Orally Active Multi-Functional Antioxidants Delay Cataract Formation in Streptozotocin (Type 1) Diabetic and Gamma-Irradiated Rats

Age-related cataract is a worldwide health care problem whose progression has been linked to oxidative stress and the accumulation of redox-active metals. Since there is no specific animal model for human age-related cataract, multiple animal models must be used to evaluate potential therapies that may delay and/or prevent cataract formation.Proof of concept studies were conducted to evaluate 4-(5-hydroxypyrimidin-2-yl)-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 4) and 4-(5-hydroxy-4,6-dimethoxypyrimidin-2-yl)-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 8), multi-functional antioxidants that can independently chelate redox metals and quench free radicals, on their ability to delay the progression of diabetic "sugar" cataracts and gamma radiation-induced cataracts. Prior to 15 Gy of whole head irradiation, select groups of Long Evans rats received either diet containing compound 4 or 8, or a single i.p. injection of panthethine, a radioprotective agent. Compared to untreated, irradiated rats, treatment with pantethine, 4 and 8 delayed initial lens changes by 4, 47, and 38 days, respectively, and the average formation of posterior subcapsular opacities by 23, 53 and 58 days, respectively. In the second study, select groups of diabetic Sprague Dawley rats were administered chow containing compounds 4, 8 or the aldose reductase inhibitor AL1576. As anticipated, treatment with AL1576 prevented cataract by inhibiting sorbitol formation in the lens. However, compared to untreated rats, compounds 4 and 8 delayed vacuole formation by 20 days and 12 days, respectively, and cortical cataract formation by 8 and 3 days, respectively, without reducing lenticular sorbitol. Using in vitro lens culture in 30 mM xylose to model diabetic "sugar" cataract formation, western blots confirmed that multi-functional antioxidants reduced endoplasmic reticulum stress.Multi-functional antioxidants delayed cataract formation in two diverse rat models. These studies provide a proof of concept that a general cataract treatment focused on reducing oxidative stress instead of a specific mechanism of cataractogenesis can be developed

Terrain, politics, history

This article is based on the 2019 Dialogues in Human Geography plenary lecture at the Royal Geographical Society. It has four parts. The first discusses my work on territory in relation to recent work by geographers and others on the vertical, the volumetric, the voluminous, and the milieu as ways of thinking space in three-dimensions, of a fluid and dynamic earth. Second, it proposes using the concept of terrain to analyse the political materiality of territory. Third, it adds some cautions to this, through thinking about the history of the concept of terrain in geographical thought, which has tended to associate it with either physical or military geography. Finally, it suggests that this work is a way geographers might begin to respond to the challenge recently made by Bruno Latour, where he suggests that ‘belonging to a territory is the phenomenon most in need of rethinking and careful redescription; learning new ways to inhabit the Earth is our biggest challenge’. Responding to Latour continues this thinking about the relations between territory, Earth, land, and ground, and their limits

Rethinking global governance: A China model in the making?

This paper examines Chinese perspectives on global governance, an area in which China has increased substantially the depth and breadth of its participation. The paper attempts to draw a mainstream perspective to inform our understanding of some key aspects of China's foreign policy. It demonstrates that while China's statist preference appeals to some Third World countries, such a preference leads the country to clash with the West over how to tackle global issues collectively, particularly over humanitarian intervention. While the Chinese perspective is in the process of evolving and far from reaching maturity, it is questionable whether the global community led by the West would find the Westphalian practice that China embraces admirabl

Depth and medium-scale spatial processes influence fish assemblage structure of unconsolidated habitats in a subtropical marine park

Where biological datasets are spatially limited, abiotic surrogates have been advocated to inform objective planning for Marine Protected Areas. However, this approach assumes close correlation between abiotic and biotic patterns. The Solitary Islands Marine Park, northern NSW, Australia, currently uses a habitat classification system (HCS) to assist with planning, but this is based only on data for reefs. We used Baited Remote Underwater Videos (BRUVs) to survey fish assemblages of unconsolidated substrata at different depths, distances from shore, and across an along-shore spatial scale of 10 s of km (2 transects) to examine how well the HCS works for this dominant habitat. We used multivariate regression modelling to examine the importance of these, and other environmental factors (backscatter intensity, fine-scale bathymetric variation and rugosity), in structuring fish assemblages. There were significant differences in fish assemblages across depths, distance from shore, and over the medium spatial scale of the study: together, these factors generated the optimum model in multivariate regression. However, marginal tests suggested that backscatter intensity, which itself is a surrogate for sediment type and hardness, might also influence fish assemblages and needs further investigation. Species richness was significantly different across all factors: however, total MaxN only differed significantly between locations. This study demonstrates that the pre-existing abiotic HCS only partially represents the range of fish assemblages of unconsolidated habitats in the region

Towards a Postsecular International Politics

The thriving debate on religion in international politics has recently seen the emergence of the postsecular as a new object of study. This is an attempt to move beyond the secular/religious divide, a foundational dimension of Western modernity, to account for a momentous transformation of the international system which affects existing forms of political community, identity, and power. At the heart of this transformation is the progressive blurring of the boundary between the secular and the religious; the clash of secular and postsecular formations; the emergence of new forms of political community characterized by a reconsideration of traditional secular and religious sources of authority, legitimacy, and power; and the emergence of new identities which challenge existing secular and religious formations by drawing on postsecular imaginaries