Chromosome instability and deregulated proliferation: an unavoidable duo

The concept that aneuploidy is a characteristic of malignant cells has long been known; however, the idea that aneuploidy is an active contributor to tumorigenesis, as opposed to being an associated phenotype, is more recent in its evolution. At the same time, we are seeing the emergence of novel roles for tumor suppressor genes and oncogenes in genome stability. These include the adenomatous polyposis coli gene (APC), p53, the retinoblastoma susceptibility gene (RB1), and Ras. Originally, many of these genes were thought to be tumor suppressive or oncogenic solely because of their role in proliferative control. Because of the frequency with which they are disrupted in cancer, chromosome instability caused by their dysfunction may be more central to tumorigenesis than previously thought. Therefore, this review will highlight how the proper function of cell cycle regulatory genes contributes to the maintenance of genome stability, and how their mutation in cancer obligatorily connects proliferation and chromosome instability.     

Forecasting stock market volatility using (non-linear) Garch models

In this paper we study the performance of the GARCH model and two of its non-linear modifications to forecast weekly stock market volatility. The models are the Quadratic GARCH (Engle and Ng, 1993) and the Glosten, Jagannathan and Runkle (1992) models which have been proposed to describe, for example, the often observed negative skewness in stock market indices. We find that the QGARCH model is best when the estimation sample does not contain extreme observations such as the 1987 stock market crash and that the GJR model cannot be recommended for forecasting.     

Characterization of a set of abdominal neuroendocrine cells that regulate stress physiology using colocalized diuretic peptides in <Emphasis Type="Italic">Drosophila</Emphasis>

Multiple neuropeptides are known to regulate water and ion balance in Drosophila melanogaster. Several of these peptides also have other functions in physiology and behavior. Examples are corticotropin-releasing factor-like diuretic hormone (diuretic hormone 44; DH44) and leucokinin (LK), both of which induce fluid secretion by Malpighian tubules (MTs), but also regulate stress responses, feeding, circadian activity and other behaviors. Here, we investigated the functional relations between the LK and DH44 signaling systems. DH44 and LK peptides are only colocalized in a set of abdominal neurosecretory cells (ABLKs). Targeted knockdown of each of these peptides in ABLKs leads to increased resistance to desiccation, starvation and ionic stress. Food ingestion is diminished by knockdown of DH44, but not LK, and water retention is increased by LK knockdown only. Thus, the two colocalized peptides display similar systemic actions, but differ with respect to regulation of feeding and body water retention. We also demonstrated that DH44 and LK have additive effects on fluid secretion by MTs. It is likely that the colocalized peptides are coreleased from ABLKs into the circulation and act on the tubules where they target different cell types and signaling systems to regulate diuresis and stress tolerance. Additional targets seem to be specific for each of the two peptides and subserve regulation of feeding and water retention. Our data suggest that the ABLKs and hormonal actions are sufficient for many of the known DH44 and LK functions, and that the remaining neurons in the CNS play other functional roles.     

Coupled major and trace elements as indicators of the extent of melting in mid-ocean-ridge peridotites

Rocks in the Earth's uppermost sub-oceanic mantle, known as abyssal peridotites, have lost variable but generally large amounts of basaltic melt, which subsequently forms the oceanic crust. This process preferentially removes from the peridotite some major constituents such as aluminium, as well as trace elements that are incompatible in mantle minerals (that is, prefer to enter the basaltic melt), such as the rare-earth elements. A quantitative understanding of this important differentiation process has been hampered by the lack of correlation generally observed between major- and trace-element depletions in such peridotites. Here we show that the heavy rare-earth elements in abyssal clinopyroxenes that are moderately incompatible are highly correlated with the Cr/(Cr + Al) ratios of coexisting spinels. This correlation deteriorates only for the most highly incompatible elements-probably owing to late metasomatic processes. Using electron- and ion-microprobe data from residual abyssal peridotites collected on the central Indian ridge, along with previously published data, we develop a quantitative melting indicator for mantle residues. This procedure should prove useful for relating partial melting in peridotites to geodynamic variables such as spreading rate and mantle temperature.     

The corticomotoneurone connection is normal in Parkinson's disease

Voluntary movements in Parkinson's disease are initiated and executed slowly. It is assumed that the motor cortex and its output pathway are intact and that bradykinesia is due to abnormal motor commands delivered to a normal corticospinal system. We have tested this assumption using electrical stimulation of the motor cortex through the scalp in three patients with severe Parkinson's disease, studied during fluctuations from relatively normal mobility when receiving drugs (ON) to severe bradykinesia when not receiving drugs (OFF). Thresholds and latencies for motor cortex stimulation to excite thumb flexor muscles and the resulting fast mechanical responses were the same in both ON and OFF conditions, even though the patients were unable to execute fast thumb flexion movements voluntarily when OFF. We conclude that the excitability and conduction velocity of the corticospinal motor pathways are normal in Parkinson's disease.     

Biogeography: molecular trails from hitch-hiking snails

Darwin was fascinated by the transportation of land snails across great swathes of open ocean by birds--he even immersed snails in sea water to see how long they would survive. Here we follow a molecular phylogenetic trail that reveals the incredible transequatorial dispersal of the land snail Balea from Europe to the Azores and the Tristan da Cunha islands, and back again. This long-distance dispersal is unexpected for what are proverbially considered the most pedestrian of creatures.