Increase of neuronal cell vulnerability by presenilin-2 (PS2) mutation by increase of caspase-3 activity through ryanodine receptor-mediated perturbation of calcium homeostasis was investigated. Stably transfected PC12 cells and cortical neurons from transgenic mice expressing mutant PS2 (N141I) showed a significantly enhanced sensitivity to L-glutamate, Aβ 25-35 , and Aβ 1-42 (ADDLs form) compared with cells expressing wild-type PS2. Consistent with this result, much greater intracellular calcium levels and caspase-3 activity were found in PC12 cells and cortical neurons expressing mutant PS2 after treatment with L-glutamate, Aβ 25-35 , and Aβ 1-42 . Double-labeling confocal micrographic and coimmunoprecipitation analyses showed that ryanodine receptor type 3 (RyR) and PS2 colocalize in the endoplasmic reticulum (ER) in PC12 cells and in the brain of transgenic mice. The expression of RyR was much higher in the neurons of cells expressing mutant PS2. Moreover, pretreatment with dantrolene, an agent that blocks calcium release from RyR, protected against the mutant PS2-enhanced neuronal cell death and caspase-3 activity. The present data indicate that activation of caspase-3 by RyR-mediated increase of intracellular calcium levels may be an important neurotoxic mechanism in the neuronal cells expressing mutant PS2.

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Two short gravity cores were retrieved to obtain palaeoclimatic information from Maxwell and Admiralty bays, King George Island, South Shetland Islands. AMS 14C age dates, sediment properties (grain size, TOC and CaCO3) and stable oxygen and carbon isotope compositions of benthiδ foraminifera (Globocassidulina biora) show downcore variations that characterize depositional conditions during the late Holocene. In particular, δ18O values of benthic foraminifera are lowest at approximately 2500 yr bp in both cores. Allowδ18O time-equivalent excursion in both cores is interpreted to reflect a distinct subglacial meltwater discharge intensified by warm climatic conditions. An increased proportion of fine-grained detritus and higher TOC in the cores at this level suggests that enhanced meltwater supply may have resulted in increased primary productivity. This meltwater discharge event provides evidence of climatic instability during the late Holocene at King George Island.

Micropaleontological investigation of four sites drilled by Ocean Drilling Program Leg 159 on the Côte d'Ivoire-Ghana Margin indicates that the initial invasion of oceanic surface waters into the Deep Ivorian Basin, as indicated by the presence of calcareous nannofossils, occurred during the late Albian. The nature of these assemblages suggests that these first Cretaceous oceanic surface waters were warm and relatively high in nutrients. These upper Albian sediments were deposited prior to significant tectonism at some of the sites, as indicated by their structurally deformed nature. The likely age of this tectonism is Cenomanian. The Upper Cretaceous consists of condensed sequences of hemipelagic carbonates and phosphatic hardgrounds with very low sediment accumulation rates overlain, at Site 959, by non-calcareous claystones. These Turonian through Santonian hemipelagic carbonates contain nannofossil assemblages that suggest low surface water nutrient content, resulting in starved basin conditions.

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