Tracking the Cracking: A Holistic Analysis of Rapid Ice Shelf Fracture Using Seismology, Geodesy, and Satellite Imagery on the Pine Island Glacier Ice Shelf, West Antarctica.

Ice shelves regulate the stability of marine ice sheets. We track fractures on Pine Island Glacier, a quickly accelerating glacier in West Antarctica that contributes more to sea level rise than any other glacier. Using an on-ice seismic network deployed from 2012 to 2014, we catalog icequakes that dominantly consist of flexural gravity waves. Icequakes occur near the rift tip and in two distinct areas of the shear margin, and TerraSAR-X imagery shows significant fracture in each source region. Rift-tip icequakes increase with ice speed, linking rift fracture to glaciological stresses and/or localized thinning. Using a simple flexural gravity wave model, we deconvolve wave propagation effects to estimate icequake source durations of 19.5-50.0 s and transient loads of 3.8-14.0 kPa corresponding to 4.3-15.9 m of crevasse growth per icequake. These long-source durations suggest that water flow may limit the rate of crevasse opening.

Effects of dopamine metabolites on locomotor activities and on the binding of dopamine: relevance to the side effects of L-dopa.

L-dopa is the major treatment for Parkinson's disease (PD), but its efficacy is limited by the presence of dyskinesia. The dyskinesia develops over a period of exposure to L-dopa and is related to the dosage, therefore, the cause may involve inductive changes that produce toxic levels of metabolites, interfering with dopamine (DA) neurotransmission. Chronic L-dopa induces catechol-O-methyltransferase (COMT) and methionine adenosyl transferase (MAT), enzymes involved in the methylation of catecholamines (CA). In addition, high levels of 3-O-methyl-dopa have been reported in the plasma of dyskinetic PD patients, treated with L-dopa, as compared to non-dyskinetic patients, therefore, the methyl metabolites of CA may be increased during L-dopa therapy and may be involved in the dyskinesia. Since large amounts of DA are produced from L-dopa, and DA is extensively methylated, the methyl metabolites of DA, 3-methoxytyramine (3-MT) and 3,4-dimethoxyphenylethylamine (DIMPEA), may be also involved. The first step in knowing this, is to assess the behavioral and DA-receptor activities of 3-MT and DIMPEA. In the rat, the intraventricular injection of 0.5 micromol of DIMPEA increased the total distance traveled (TD) by over 100%, the number of movement (NM) made by 40% and the time spent moving (MT) by about 36%. Identical doses of 3-MT decreased the TD by 42%, NM by 22% and MT by 39%. DIMPEA (1 mM) increased the binding of DA with brain membranes by 44.7%, whereas 3-MT decreased it by 15.8%. The results show that 3-MT and DIMPEA are behaviorally active, and in parallel, they interact with the binding sites for DA, consequently, they may contribute to the side effects of L-dopa. L-dopa produces high levels of DA and induces MAT and COMT. It is proposed, therefore, that DA will be methylated to 3-MT and 3-MT to DIMPEA. At threshold level each product will inhibit, allosterically, its enzyme of methylation, causing sequential and rhythmic up and down regulation of its concentration. At peak levels these hydrophobic metabolites will modulate the actions of DA on synaptic membranes, causing abnormal movements, at times, resembling the "on-off effects".

Striatal dopamine depletion, tremors, and hypokinesia following the intracranial injection of S-adenosylmethionine: a possible role of hypermethylation in parkinsonism.

The major symptoms of Parkinson disease (PD) are tremors, hypokinesia, rigidity, and abnormal posture, caused by the degeneration of dopamine (DA) neurons in the substantia nigra (SN) and deficiency of DA in the neostriatal DA terminals. Norepinephrine (NE) and serotonin (5-HT) levels in the neostriatum and tyrosine hydroxylase and melanin pigments in the substantia nigra are also decreased, and brain cholinergic activity is increased. The cause of PD is unknown, but PD is an age-related disorder, suggesting that changes that occur during the aging process may help to precipitate PD. Methylation increases in aging animals. Increased methylation can deplete DA, NE, and 5-HT; increase acetylcholine; and cause hypokinesia and tremors. These effects are similar to changes seen in PD, and interestingly also, they are similar to some of the changes that are associated with the aging process. It is suggested, therefore, that increased methylation may be an inducing factor in parkinsonism. Accordingly, the effects of an increase in methylation in the brain of rats were studied. S-adenosylmethionine (AdoMet), the limiting factor in the methylation process, was injected into the lateral ventricle of rats. Specific behavioral changes that resemble changes seen in PD were investigated. The results showed that AdoMet caused tremors, rigidity, hypokinesia, and depleted DA. The hypokinetic effects of a single dose of AdoMet lasted for about 90 min. AdoMet has a dose-dependent hypokinetic effect. A dose of 9.4 nmol reduced movement time (MT) by 68.9% and increased rest time (RT) by 20.7%, and a dose of 400 nmol reduced MT by 92.4% and increased RT by 27.6%. The normethyl analog of AdoMet, S-adenosylhomocysteine, did not cause hypokinesia or tremors, but it blocked the AdoMet-induced motor effects. L-dopa, the precursor of DA, also blocked the AdoMet-induced motor effects. These data suggest that the methyl group of AdoMet as well as DA depletion are involved in the AdoMet-induced motor effects. A dose of 0.65 mumol of AdoMet depleted DA in the ipsilateral caudate nucleus (CN) or neostriatum by 50.1%, and DA in the contralateral CN was reduced by 9.3%. Double the dose of AdoMet did not increase the depletion of DA on the ipsilateral CN, but DA in the contralateral CN was decreased by 26.3%. Taken together, the results suggest that increased methylation may contribute to the symptoms of PD.