Post-stroke inhibition of induced NADPH oxidase type 4 prevents oxidative stress and neurodegeneration

Ischemic stroke is the second leading cause of death worldwide. Only one moderately effective therapy exists, albeit with contraindications that exclude 90% of the patients. This medical need contrasts with a high failure rate of more than 1,000 pre-clinical drug candidates for stroke therapies. Thus, there is a need for translatable mechanisms of neuroprotection and more rigid thresholds of relevance in pre-clinical stroke models. One such candidate mechanism is oxidative stress. However, antioxidant approaches have failed in clinical trials, and the significant sources of oxidative stress in stroke are unknown. We here identify NADPH oxidase type 4 (NOX4) as a major source of oxidative stress and an effective therapeutic target in acute stroke. Upon ischemia, NOX4 was induced in human and mouse brain. Mice deficient in NOX4 (Nox4(-/-)) of either sex, but not those deficient for NOX1 or NOX2, were largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia. This effect was independent of age, as elderly mice were equally protected. Restoration of oxidative stress reversed the stroke-protective phenotype in Nox4(-/-) mice. Application of the only validated low-molecular-weight pharmacological NADPH oxidase inhibitor, VAS2870, several hours after ischemia was as protective as deleting NOX4. The extent of neuroprotection was exceptional, resulting in significantly improved long-term neurological functions and reduced mortality. NOX4 therefore represents a major source of oxidative stress and novel class of drug target for stroke therapy

HST UV Observations of Asteroid (16) Psyche

The Main Belt Asteroid (16) Psyche is the target object of the NASA Discovery Mission Psyche. We observed the asteroid at ultraviolet (UV) wavelengths (170-310 nm) using the Space Telescope Imaging Spectrograph on the Hubble Space Telescope during two separate observations. We report that the spectrum is very red in the UV, with a blue upturn shortward of similar to 200 nm. We find an absorption feature at 250 nm and a weaker absorption feature at 275 nm that may be attributed to a metal-oxide charge transfer band. We find that the red-sloped, relatively featureless spectrum of (16) Psyche is best matched with the reflectance spectrum of pure iron; however, our intimate mixture models show that small grains of iron may dominate the reflectance spectrum even if iron only comprises up to 10% of the material on the surface. We also stress that there is a limited database of reflectances for planetary surface analogs at UV wavelengths for comparison with the spectrum of (16) Psyche. The mid- and far-UV spectra (<240 nm) are markedly different for each of the four asteroids observed at these wavelengths so far, including ones in the same spectral class, indicating that UV observations of asteroids could be used to better understand differences in the composition and processing of the surfaces of these small bodies

Legacies of empire: state violence and collective punishment in Kenya's North Eastern Province, c. 1963-present

This article reflects on the dual historical evolution of the use of state violence and collective punishment in Kenya, with particular reference to the Somali inhabited North Eastern Province. The use of collective punishment began under British rule as a strategy designed to control its African population, and was central to British counterinsurgency during the 1950s Mau Mau Emergency. This system of government was then entrenched and expanded by the postcolonial elite as a means of dealing with a population that was perceived to be hostile to the interests of the state. The article provides evidence of both colonial continuities and discontinuities with regard to population control methods

Legacies of empire: state violence and collective punishment in Kenya's North Eastern Province, c. 1963-present

This article reflects on the dual historical evolution of the use of state violence and collective punishment in Kenya, with particular reference to the Somali inhabited North Eastern Province. The use of collective punishment began under British rule as a strategy designed to control its African population, and was central to British counterinsurgency during the 1950s Mau Mau Emergency. This system of government was then entrenched and expanded by the postcolonial elite as a means of dealing with a population that was perceived to be hostile to the interests of the state. The article provides evidence of both colonial continuities and discontinuities with regard to population control methods