ALBERT

Description: We present results from the largest contiguous narrow-band survey in the near-infrared. We have used the wide-field infrared camera/Canada–France–Hawaii Telescope and the lowOH2 filter (1.187 ± 0.005 μm) to survey 10 deg 2 of contiguous extragalactic sky in the SA22 field. A total of ~6000 candidate emission-line galaxies are found. We use deep ugrizJK data to obtain robust photometric redshifts. We combine our data with the High-redshift(Z) Emission Line Survey (HiZELS), explore spectroscopic surveys (VVDS, VIPERS) and obtain our own spectroscopic follow-up with KMOS, FMOS and MOSFIRE to derive large samples of high-redshift emission-line selected galaxies: 3471 Hα emitters at z  = 0.8, 1343 [O iii ] + Hβ emitters at z  = 1.4 and 572 [O ii ] emitters at z  = 2.2. We probe comoving volumes of 〉10 6  Mpc 3 and find significant overdensities, including an 8.5 (spectroscopically confirmed) overdensity of Hα emitters at z  = 0.81. We derive Hα, [O iii ] + Hβ and [O ii ] luminosity functions at z  = 0.8, 1.4, 2.2, respectively, and present implications for future surveys such as Euclid . Our uniquely large volumes/areas allow us to subdivide the samples in thousands of randomized combinations of areas and provide a robust empirical measurement of sample/cosmic variance. We show that surveys for star-forming/emission-line galaxies at a depth similar to ours can only overcome cosmic-variance (errors 〈10 per cent) if they are based on volumes 〉5  x  10 5  Mpc 3 ; errors on L * and * due to sample (cosmic) variance on surveys probing ~10 4 and ~10 5  Mpc 3 are typically very high: ~300 and ~40–60 per cent, respectively.

Description: Niemann-Pick type C (NPC) disease, an autosomal recessive disorder caused primarily by loss-of-function mutations in NPC1 gene, is characterized neuropathologically by intracellular cholesterol accumulation, gliosis and neuronal loss in selected brain regions. Recent studies have shown that NPC disease exhibits intriguing parallels with Alzheimer's disease (AD), including the presence of tau-positive neurofibrillary tangles (NFTs) and β-amyloid (Aβ)-related peptides in vulnerable brain regions. Since enhanced cholesterol level, which acts as a risk factor for AD, can increase Aβ production by regulating amyloid precursor protein (APP) metabolism, it is possible that APP overexpression can influence cholesterol-regulated NPC pathology. We have addressed this issue in a novel bigenic mice (ANPC) generated by crossing heterozygous Npc1-deficient mice with mutant human APP transgenic mice. These mice exhibited decreased lifespan, early object memory and motor impairments, and exacerbated glial pathology compared with other littermates. Neurodegeneration observed in the cerebellum of ANPC mice was found to be accelerated along with a selective increase in the phosphorylation/cleavage of tau protein. Additionally, enhanced levels/activity of cytosolic cathepsin D together with cytochrome c and Bcl-2-associated X protein suggest a role for the lysosomal enzyme in the caspase-induced degeneration of neurons in ANPC mice. The reversal of cholesterol accretion by 2-hydroxypropyl-β-cyclodextrin (2-HPC) treatment increased longevity and attenuated behavioral/pathological abnormalities in ANPC mice. Collectively, our results reveal that overexpression of APP in Npc1-deficient mice can negatively influence longevity and a wide spectrum of behavioral/neuropathological abnormalities, thus raising the possibility that APP and NPC1 may interact functionally to regulate the development of AD and NPC pathologies.