Increased Production of Paired Helical Filament Epitopes in a Cell Culture System Reduces the Turnover of τ

Abstract: To investigate the regulation of posttranslational modifications of τ that might be pertinent to the production of the paired helical filament (PHF) of Alzheimer's disease, we incubated human neuroblastoma cells with the protein phosphatase inhibitor okadaic acid. This treatment results in increased immunoreactivity of τ with the monoclonal antibodies Alz-50, PHF-1, T3P, and NP8, a reduction in Tau-1 immunoreactivity, and an elevation in apparent molecular weight of τ. Moreover, our data demonstrate that accumulation of phosphates in τ leads to a decrease in the turnover rate of τ in the neuroblastoma cells. It is suggested that similar build-up of hyperphosphorylated τ in the neuronal perikarya may represent an early event in PHF formation. The present system facilitates the investigation of regulatory mechanisms governing the occurrence of PHF epitopes, their effects on neuronal cell metabolism, and possible pharmacological intervention.     

Reproductive Dynamics and Potential Annual Fecundity of South Pacific Albacore Tuna (Thunnus alalunga)

The reproductive biology of albacore tuna, Thunnus alalunga, in the South Pacific Ocean was investigated with samples collected during broad-scale sampling between 2006 and 2011. Histology was done in a single laboratory according to standard protocols and the data analysed using generalized linear mixed-effects models. The sex ratio of albacore was female biased for fish smaller than approximately 60 cm FL and between 85 and 95 cm, and progressively more male biased above 95 cm FL. Spawning activity was synchronised across the region between 10°S and 25°S during the austral spring and summer where sea surface temperatures were ≥24 °C. The average gonad index varied among regions, with fish in easterly longitudes having heavier gonads for their size than fish in westerly longitudes. Albacore, while capable of spawning daily, on average spawn every 1.3 days during the peak spawning months of October to December. Spawning occurs around midnight and the early hours of the morning. Regional variation in spawning frequency and batch fecundity were not significant. The proportion of active females and the spawning fraction increased with length and age, and mature small and young fish were less active at either end of the spawning season than larger, older fish. Batch fecundity estimates ranged from 0.26 to 2.83 million oocytes with a mean relative batch fecundity of 64.4 oocytes per gram of body weight. Predicted batch fecundity and potential annual fecundity increased with both length and age. This extensive set of reproductive parameter estimates provides many of the first quantitative estimates for this population and will substantially improve the quality of biological inputs to the stock assessment for South Pacific albacore.     

Quantitative determination of conformational disorder in the acyl chains of phospholipid bilayers by infrared spectroscopy

A method is proposed and demonstrated for the direct determination of conformational disorder (trans-gauche isomerization) as a function of acyl-chain position in phospholipid bilayer membranes. Three specifically deuterated derivatives of dipalmitoylphosphatidylcholine (DPPC), namely 4,4,4',4'-d4-DPPC (4-d4-DPPC), 6,6,6',6'-d4-DPPC (6-d4-DPPC), and 10,10,10',10'-d4-DPPC (10-d4-DPPC), have been synthesized. The CD2 rocking modes in the Fourier transform infrared (FT-IR) spectrum have been monitored as a function of temperature for each derivative. A method originally applied by Snyder and Poore [(1973) Macromolecules 6, 708-715] as a specific probe of hydrocarbon chain conformation in alkanes has been used to analyze the data. The rocking modes appear at 622 cm-1 for a CD2 segment surrounded by a trans C-C-C skeleton and between 645 and 655 cm-1 for segments surrounded by particular gauche conformers. The integrated band intensities of these modes have been used to monitor trans-gauche isomerization in the acyl chains at particular depths in the bilayer. At 48 degrees C, above the gel-liquid-crystal phase transition, the percentage of gauche rotamers present is 20.7 +/- 4.2, 32.3 +/- 2.3, and 19.7 +/- 0.8 for 4-d4-DPPC, 6-d4-DPPC, and 10-d4-DPPC, respectively. The gel phase of the latter two molecules is highly ordered. In contrast, a substantial population of gauche rotamers was observed for the 4-d4-DPPC. The conformational analysis yields a range of 3.6-4.2 gauche rotamers/acyl chain of DPPC above the phase transition. This range is in excellent accord with the dilatometric data of Nagle and Wilkinson [(1978) Biophys. J. 23, 159-175]. The significant advantages of the FT-IR approach are discussed.     

An anchored molecular map of mouse Chromosome 6 with an analysis of interference

The haplotype data reported in this paper have been submitted to (MGD) and have been assigned the accession numbers: MGD-CREX-235 (back-cross data); MGD-CREX-236 (intercross data).