- Email: [email protected]
Proteome efforts to follow Genome reports
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could be compared to studies of LTP, which implicate a local MAPK action for regulating LTP induction, and both dendritic and nuclear targets for regulating late phases of LTP. It is difficult, however, to relate the relatively long-duration stimuli and interstimulus intervals used by Wu et al. to synaptic activity mediating LTP or in vivo learning. Furthermore, it is not clear why multiple spaced stimuli induce sustained MAPK activation and spine and filopodia growth, whereas a single long pulse does not. Wu et al. show that Ca2+ transients
TRENDS in Neurosciences Vol.24 No.5 May 2001
257
during depolarization rapidly decay, even though depolarization persists. Therefore, spaced, shorter stimuli could yield greater Ca2+ influx compared with single long stimuli, which might be needed to activate PKA. Also, it should be clear that the meanings of the terms ‘spaced’ and ‘massed’ used by Wu et al. differ significantly from, and therefore should not be associated with, their use in behavioral learning paradigms. Wu et al. have provided an important bridge between activitydependent stimulation of MAPK and spine
and filopodia growth, strengthening the model that MAPK stores the memory of neuronal activity during the transition from early forms of LTP mediated by receptor modulation to longer-lasting structural changes.
Src, which upregulates NMDA receptor function via tyrosine phosphorylation. These events also occur secondary to tetanic stimuli and are necessary events for LTP induction.
involved in the litigation. In order to facilitate the selection of less-biased experts, the AAAS will take suggestions by professional associations and will have a panel of advisors to make selections based on both scientific credentials and the ability to communicate to a lay audience. The expert, who will be paid by the court, will be revealed only when the appointment becomes part of the public record. The project, called CASE for Court-Appointed Scientific Experts, was launched in February.
1 Wu, G-Y. et al. (2001) Spaced stimuli stabilize MAPK pathway activation and its effects on dendritic morphology. Nat. Neurosci. 4, 151–158
Kurt Haas [email protected]
In Brief
Proteome efforts to follow Genome reports
New LTP molecule Enhanced NMDA receptor activity is responsible for the induction of LTP in hippocampus, but exactly how NMDA receptor activity is upregulated is unknown. It is known that protein kinase C (PKC) activity leads to increased NMDA receptor currents, similar to NMDA receptor phosphorylation by Src. Now, researchers from Toronto, Canada and Sapporo, Japan report in the February issue of Neuron that another non-receptor kinase called cell adhesion kinase β/proline-rich tyrosine kinase 2 (CAKβ/Pyk2) is an additional intermediary signal. CAKβ/Pyk2 can be activated by both Ca2+ and PKC, and is associated with the NMDA receptor complex in the postsynaptic density. Electrophysiological data using CAKβ/Pyk2 or a mutant dominant-negative of the kinase, in addition to PKC and Src activators or inhibitors, are consistent with the scheme that PKC-activated CAKβ/Pky2 activates
In the wake of the publication of the human genomic sequences in February issues of Science and Nature, attention is now moving from the genes to the proteins they encode. An international Human Proteome Organization, modeled after the Human Genome Organization, has been established to coordinate the efforts to understand the function and expression patterns of these new proteins. Because over 10 000 of genes in the human genome are thought to be involved in the development and function of the brain, neuroscientists in particular will have much to gain by these efforts. The first meeting of the organization is planned for this upcoming spring.
AD gene accelerates MS
Scientific expertise in law A new project developed by the American Association for the Advancement of Science (AAAS) and the American Bar Associations Science and Technology Law Section will help US federal judges find impartial scientists and engineers to explain complex technical information in trials. In spite of the right of federal judges to appoint experts and a 1993 US Supreme Court ruling requiring them to exclude unreliable testimonies, AAAS studies found that testimonies usually come from experts chosen and paid by parties
An interesting connection between two neurologic diseases – Alzheimer’s disease (AD) and multiple sclerosis (MS) – have been linked in a recent study reported in the February 13 issue of Neurology. Researchers at Tel Aviv University in Israel used disability status tests to study 205 MS patients over several years. They found that MS patients who also carried the APOE4 gene, which predisposes people to AD, had MS an average of three years earlier and suffered a quicker and
http://tins.trends.com 0166-2236/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.
could be compared to studies of LTP, which implicate a local MAPK action for regulating LTP induction, and both dendritic and nuclear targets for regulating late phases of LTP. It is difficult, however, to relate the relatively long-duration stimuli and interstimulus intervals used by Wu et al. to synaptic activity mediating LTP or in vivo learning. Furthermore, it is not clear why multiple spaced stimuli induce sustained MAPK activation and spine and filopodia growth, whereas a single long pulse does not. Wu et al. show that Ca2+ transients
TRENDS in Neurosciences Vol.24 No.5 May 2001
257
during depolarization rapidly decay, even though depolarization persists. Therefore, spaced, shorter stimuli could yield greater Ca2+ influx compared with single long stimuli, which might be needed to activate PKA. Also, it should be clear that the meanings of the terms ‘spaced’ and ‘massed’ used by Wu et al. differ significantly from, and therefore should not be associated with, their use in behavioral learning paradigms. Wu et al. have provided an important bridge between activitydependent stimulation of MAPK and spine
and filopodia growth, strengthening the model that MAPK stores the memory of neuronal activity during the transition from early forms of LTP mediated by receptor modulation to longer-lasting structural changes.
Src, which upregulates NMDA receptor function via tyrosine phosphorylation. These events also occur secondary to tetanic stimuli and are necessary events for LTP induction.
involved in the litigation. In order to facilitate the selection of less-biased experts, the AAAS will take suggestions by professional associations and will have a panel of advisors to make selections based on both scientific credentials and the ability to communicate to a lay audience. The expert, who will be paid by the court, will be revealed only when the appointment becomes part of the public record. The project, called CASE for Court-Appointed Scientific Experts, was launched in February.
1 Wu, G-Y. et al. (2001) Spaced stimuli stabilize MAPK pathway activation and its effects on dendritic morphology. Nat. Neurosci. 4, 151–158
Kurt Haas [email protected]
In Brief
Proteome efforts to follow Genome reports
New LTP molecule Enhanced NMDA receptor activity is responsible for the induction of LTP in hippocampus, but exactly how NMDA receptor activity is upregulated is unknown. It is known that protein kinase C (PKC) activity leads to increased NMDA receptor currents, similar to NMDA receptor phosphorylation by Src. Now, researchers from Toronto, Canada and Sapporo, Japan report in the February issue of Neuron that another non-receptor kinase called cell adhesion kinase β/proline-rich tyrosine kinase 2 (CAKβ/Pyk2) is an additional intermediary signal. CAKβ/Pyk2 can be activated by both Ca2+ and PKC, and is associated with the NMDA receptor complex in the postsynaptic density. Electrophysiological data using CAKβ/Pyk2 or a mutant dominant-negative of the kinase, in addition to PKC and Src activators or inhibitors, are consistent with the scheme that PKC-activated CAKβ/Pky2 activates
In the wake of the publication of the human genomic sequences in February issues of Science and Nature, attention is now moving from the genes to the proteins they encode. An international Human Proteome Organization, modeled after the Human Genome Organization, has been established to coordinate the efforts to understand the function and expression patterns of these new proteins. Because over 10 000 of genes in the human genome are thought to be involved in the development and function of the brain, neuroscientists in particular will have much to gain by these efforts. The first meeting of the organization is planned for this upcoming spring.
AD gene accelerates MS
Scientific expertise in law A new project developed by the American Association for the Advancement of Science (AAAS) and the American Bar Associations Science and Technology Law Section will help US federal judges find impartial scientists and engineers to explain complex technical information in trials. In spite of the right of federal judges to appoint experts and a 1993 US Supreme Court ruling requiring them to exclude unreliable testimonies, AAAS studies found that testimonies usually come from experts chosen and paid by parties
An interesting connection between two neurologic diseases – Alzheimer’s disease (AD) and multiple sclerosis (MS) – have been linked in a recent study reported in the February 13 issue of Neurology. Researchers at Tel Aviv University in Israel used disability status tests to study 205 MS patients over several years. They found that MS patients who also carried the APOE4 gene, which predisposes people to AD, had MS an average of three years earlier and suffered a quicker and
http://tins.trends.com 0166-2236/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.