Partial Loss of Ataxin-1 Function Contributes to Transcriptional Dysregulation in Spinocerebellar Ataxia Type 1 Pathogenesis

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by expansion of a CAG repeat that encodes a polyglutamine tract in ATAXIN1 (ATXN1). Molecular and genetic data indicate that SCA1 is mainly caused by a gain-of-function mechanism. However, deletion of wild-type ATXN1 enhances SCA1 pathogenesis, whereas increased levels of an evolutionarily conserved paralog of ATXN1, Ataxin 1-Like, ameliorate it. These data suggest that a partial loss of ATXN1 function contributes to SCA1. To address this possibility, we set out to determine if the SCA1 disease model (Atxn1154Q/+ mice) and the loss of Atxn1 function model (Atxn1−/− mice) share molecular changes that could potentially contribute to SCA1 pathogenesis. To identify transcriptional changes that might result from loss of function of ATXN1 in SCA1, we performed gene expression microarray studies on cerebellar RNA from Atxn1−/− and Atxn1154Q/+ cerebella and uncovered shared gene expression changes. We further show that mild overexpression of Ataxin-1-Like rescues several of the molecular and behavioral defects in Atxn1−/− mice. These results support a model in which Ataxin 1-Like overexpression represses SCA1 pathogenesis by compensating for a partial loss of function of Atxn1. Altogether, these data provide evidence that partial loss of Atxn1 function contributes to SCA1 pathogenesis and raise the possibility that loss-of-function mechanisms contribute to other dominantly inherited neurodegenerative diseases

The sterols of certain tropical oils

Typescript.Thesis (Ph. D.)--University of Hawaii, 1951.Bibliography: leaves [98]-103

Chemical composition of ferromanganese nodules from the Pacific Ocean

For evaluating the efficiency of high-temperature sulfation as a potential technique used in the extraction of metals from manganese nodules, the authors have chemically analysed selected samples using atomic absorption spectroscopy. In order to match the industrial constraints of this extraction, the samples were dessicated at 100°C and then later heated at 450°C. The total H2O extracted by this two phased process has been measured, however it is worth noting that at the temperature of 450°C structural water may still be residually bounded to both Fe and Mn

Chemical analyses of a ferromanganese nodule from the Central Pacific Ocean (Cruise Mn-74-01, R/V Moana Wave)

A manganese nodule was recovered from station No. 18 of cruise Mn-74-01 of the R/V Moana Wave as part of the field work of the NSF-IDOE Inter-University Ferromanganese Research progam in 1974. The whole sample was first treated by 5M hydrochloric acid anf later digested with hydrochloric, perchloric and hydrofluoric acids. The soluble part was analysed by Atomic Absorption for nickel, cobalt and copper content

Atomic absorption spectrophotometric determination of selected elements in ferromanganese nodules from the Pacific, Atlantic, and Indian Oceans

Twenty-one samples of deep-sea ferromanganese nodules collected from the Pacific, Atlantic, and Indian oceans were supplied by the Lamont-Doherty Geological Observatory of Columbia University and the Hawaii Institute of Geophysics, University of Hawaii. The air-dried manganese nodules were crushed with the aid of a ceramic mortar and pestle, and sorted according to particle size using a set of U.S. standard mesh sieves. Powdered nodules (100/150 ?m) in particle diameter) were dried overnight at 450°C in a Lindberg furnace, and the weight loss of the sample was measured for H2O concentration determination. Exactly 500 mg of the dehydrated samples were acid-digested in a pressurized Teflon bomb and the contents were diluted to 100 ml with 0.5 M boric acid solution. Five replicates of each nodule specimen were digested and stored in polyethylene bottle. Four aliquots of the acid-digested sample were pipetted into separate beakers to which aqueous thallium standards were added successively with Eppendorf micropipettes. Each sample solution was adjusted to pH 10.8, and the wash solution was added to the separatory funnel. Five milliliters of a 1% APDC solution and 10 ml of MIBK were pipetted into each separatory funnel. The funnels were mounted on a Kraft Model S-500 mechanical shaker and shaken at a maximum amplitude for 10 min. A Perkin-EImer 603 atomic absorption spectrophotometer equipped with Westinghouse single-element hollow cathode lamps was used together with an air-acetylene oxidizing flame and a 10-cm single slot burner for all the measurements. Thallium was determined in the APDC-MIBK extract as soon as possible after the extraction step was completed, using the primary wavelength (276.8 nm), a 16 mA lamp current, and a slit setting at 4. Other metals such as Mn, Fe, Cu, Ni, and Co were measured directly in a portion of the acid-digested samples without carrying out the solvent extraction preconcentration step

Analysis of deep-sea ferromanganese nodules using particle-induced X-ray emission technique

Seven samples of ferromanganese nodules were analyzed using particle-induced X-ray emission technique (PIXE). All the samples were air-dried, crushed, and ground to a fine particle size (<100 mesh). Between 200 and 300 mg of each of the nodule samples was digested in a Teflon-lined stainless steel vessel with a 3:3:1 mixture of Ultrex HNO3, HF, and HC1 at 110 "C for several hours. A Nuclepore filter was impregnated with three 100-µL aliquots of the resulting solution and the thin target sandwiched between Kapton. The samples were irradiated with a 1-MeV proton beam for 1/2 h and the low-energy X-ray spectrum (0-10 keV) was collected. The high-energy (5-35 keV) emission spectrum obtained with a 2-MeV proton beam was collected for 1 h with a 0.004-in. A1 filter. The elemental concentrations present in the thin targets were calculated from the X-ray efficiency curves as described for the standard reference materials

Analysis of deep-sea ferromanganese nodules using flame atomic absorption and emission analysis

All the samples were air-dried, crushed, and ground to a fine particle size (<100 mesh). Flame analyses were carried out with a solution that was obtained by the digestion of a 0.5-g sample of nodules in a Teflon-lined vessel. The resulting solution was transferred to a 100-mL volumetric flask containing 70 mL of a 5% boric acid solution and diluted to the mark. Standard solutions of the elements were prepared in an identical manner with 5% boric acid solution. Atomic absorption and emission spectrophotometric analyses were carried out for 22 elements with a Varian Model 5 atomic absorption spectrophotometer. A nitrous oxide-acetylene flame was used for the determination of Al, Ba, Mo, Sr, V, Ti, and Si. Arsenic was determined with a tantalum boat and a hydrogen-nitrogen flame, and the remaining elements were determined with an ai-acetylene flame