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<jats:p> G <jats:sub>1</jats:sub> cyclin-dependent kinase (Cdk)–triggered degradation of the S-phase Cdk inhibitor Sic1p has been implicated in the transition from G <jats:sub>1</jats:sub> to S phase in the cell cycle of budding yeast. A multidimensional electrospray mass spectrometry technique was used to map G <jats:sub>1</jats:sub> Cdk phosphorylation sites in Sic1p both in vitro and in vivo. A Sic1p mutant lacking three Cdk phosphorylation sites did not serve as a substrate for Cdc34p-dependent ubiquitination in vitro, was stable in vivo, and blocked DNA replication. Moreover, purified phosphoSic1p was ubiquitinated in cyclin-depleted G <jats:sub>1</jats:sub> extract, indicating that a primary function of G <jats:sub>1</jats:sub> cyclins is to tag Sic1p for destruction. These data suggest a molecular model of how phosphorylation and proteolysis cooperate to bring about the G <jats:sub>1</jats:sub> /S transition in budding yeast. </jats:p>

<jats:p> Proteolysis mediated by the anaphase-promoting complex (APC) triggers chromosome segregation and exit from mitosis, yet its regulation is poorly understood. The conserved Cdc20 and Cdh1 proteins were identified as limiting, substrate-specific activators of APC-dependent proteolysis. <jats:italic>CDC20</jats:italic> was required for the degradation of the APC substrate Pds1 but not for that of other APC substrates, such as Clb2 and Ase1. Conversely, <jats:italic>cdh1Δ</jats:italic> mutants were impaired in the degradation of Ase1 and Clb2 but not in that of Pds1. Overexpression of either <jats:italic>CDC20</jats:italic> or <jats:italic>CDH1</jats:italic> was sufficient to induce APC-dependent proteolysis of the appropriate target in stages of the cell cycle in which substrates are normally stable. </jats:p>

<jats:p>The site of impulse initiation is crucial for the integrative actions of mammalian central neurons, but this question is currently controversial. Some recent studies support classical evidence that the impulse always arises in the soma-axon hillock region, with back-propagation through excitable dendrites, whereas others indicate that the dendrites are sufficiently excitable to initiate impulses that propagate forward along the dendrite to the soma-axon hillock. This issue has been addressed in the olfactory mitral cell, in which excitatory synaptic input is restricted to the distal tuft of a single primary dendrite. In rat olfactory bulb slices, dual whole cell recordings were made at or near the soma and from distal sites on the primary dendrite. The results show that the impulse can be initiated in either the soma-axon hillock or in the distal primary dendrite, and that the initiation site is controlled physiologically by the excitatory synaptic inputs to the distal tuft and inhibitory synaptic inputs near the soma.</jats:p>

<jats:p> Long-term potentiation (LTP) is considered an important neuronal mechanism of learning and memory. Currently, however, there is no direct experimental link between LTP of an identified synapse and learning. A cellular analog of classical conditioning in <jats:italic>Aplysia</jats:italic> was used to determine whether this form of invertebrate learning involves <jats:italic>N</jats:italic> -methyl- <jats:sc>d</jats:sc> -aspartate (NMDA)–type LTP. The NMDA receptor-antagonist <jats:sc>dl</jats:sc> -2-amino-5-phosphonovalerate significantly disrupted synaptic enhancement after associative training but did not disrupt synaptic enhancement after nonassociative training. Thus, classical conditioning in <jats:italic>Aplysia</jats:italic> appears to be mediated, in part, by LTP due to activation of NMDA-related receptors. </jats:p>

<jats:p> Inositol hexakisphosphate (InsP <jats:sub>6</jats:sub> ), the dominant inositol phosphate in insulin-secreting pancreatic β cells, inhibited the serine-threonine protein phosphatases type 1, type 2A, and type 3 in a concentration-dependent manner. The activity of voltage-gated L-type calcium channels is increased in cells treated with inhibitors of serine-threonine protein phosphatases. Thus, the increased calcium channel activity obtained in the presence of InsP <jats:sub>6</jats:sub> might result from the inhibition of phosphatase activity. Glucose elicited a transient increase in InsP <jats:sub>6</jats:sub> concentration, which indicates that this inositol polyphosphate may modulate calcium influx over the plasma membrane and serve as a signal in the pancreatic β cell stimulus-secretion coupling. </jats:p>

<jats:p>Although previous analyses indicate that neocortical neurons originate from the cortical proliferative zone, evidence suggests that a subpopulation of neocortical interneurons originates within the subcortical telencephalon. For example, γ-aminobutyric acid (GABA)–expressing cells migrate in vitro from the subcortical telencephalon into the neocortex. The number of GABA-expressing cells in neocortical slices is reduced by separating the neocortex from the subcortical telencephalon. Finally, mice lacking the homeodomain proteins DLX-1 and DLX-2 show no detectable cell migration from the subcortical telencephalon to the neocortex and also have few GABA-expressing cells in the neocortex.</jats:p>

<jats:p>A mechanism by which members of the ciliary neurotrophic factor (CNTF)–leukemia inhibitory factor cytokine family regulate gliogenesis in the developing mammalian central nervous system was characterized. Activation of the CNTF receptor promoted differentiation of cerebral cortical precursor cells into astrocytes and inhibited differentiation of cortical precursors along a neuronal lineage. Although CNTF stimulated both the Janus kinase–signal transducer and activator of transcription (JAK-STAT) and Ras–mitogen-activated protein kinase signaling pathways in cortical precursor cells, the JAK-STAT signaling pathway selectively enhanced differentiation of these precursors along a glial lineage. These findings suggest that cytokine activation of the JAK-STAT signaling pathway may be a mechanism by which cell fate is controlled during mammalian development.</jats:p>

<jats:p>Rats learn a novel foraging pattern better with their right-side whiskers than with their left-side whiskers. They also learn better with the left cerebral hemisphere than with the right hemisphere. Rotating an already learned maze relative to the external environment most strongly reduces right-whisker performance; starting an already learned maze at a different location most strongly reduces left-whisker performance. These results suggest that the right-periphery–left-hemisphere system accesses a map-like representation of the foraging problem, whereas the left-periphery–right-hemisphere system accesses a rote path. Thus, as in humans, functional asymmetries in rats can be elicited by both peripheral and cortical manipulation, and each hemisphere makes qualitatively distinct contributions to a complex natural behavior.</jats:p>