CYberinfrastructure for COmparative effectiveness REsearch (CYCORE): improving data from cancer clinical trials.

Improved approaches and methodologies are needed to conduct comparative effectiveness research (CER) in oncology. While cancer therapies continue to emerge at a rapid pace, the review, synthesis, and dissemination of evidence-based interventions across clinical trials lag in comparison. Rigorous and systematic testing of competing therapies has been clouded by age-old problems: poor patient adherence, inability to objectively measure the environmental influences on health, lack of knowledge about patients' lifestyle behaviors that may affect cancer's progression and recurrence, and limited ability to compile and interpret the wide range of variables that must be considered in the cancer treatment.

A fast synaptic potential mediated by NMDA and non-NMDA receptors.

A fast synaptic potential mediated by NMDA and non-NMDA receptors. J. Neurophysiol.

Cell-cell interactions define the innervation patterns of central leech neurons during development.

In the last 20 years, the nervous system of the developing leech has been used to great advantage to study the processes by which neurons seek and finally innervate their targets. This review summarizes what is presently known about how neurons of the CNS interact with each other and with their targets during embryogenesis.

Interactions during a critical period inhibit bilateral projections in embryonic neurons.

The anterior pagoda (AP) neurons in the CNS of the medicinal leech are found as homologous pairs in 20 of the 21 midbody ganglia. Each AP is the mirror image of its mate, extending its main axon across the midline of the CNS and eventually into the contralateral body wall, thereby attaining a unilateral pattern of innervation. Certain features of the adult AP morphology are known to arise through interactions among homologs early in development (Gao and Macagno, 1987b), but it is not known whether the contralateral nature of the projection pattern is due to intrinsic "one-sidedness" or rather to cell-cell interactions that inhibit the formation of a second, ipsilateral projection.

Postsynaptic modulation of synaptic efficacy at mixed synapses on the Mauthner cell.

Extracellular application of dopamine in the synaptic bed of the lateral dendrite of the goldfish Mauthner (M-) cell enhances both the electrical and chemical components of the mixed excitatory postsynaptic potential (EPSP) evoked by ipsilateral eighth nerve stimulation (Pereda et. al., 1992).

Calcium wave fronts that cross gap junctions may signal neuronal death during development.

Embryonic anterior pagoda (AP) neurons in the leech interact with their segmental homologs in adjacent ganglia through transient axons that overlap during a critical period of development and then retract. However, when an AP neuron is ablated mechanically or by irradiation during this period, an adjacent homolog responds by reinitiating growth of its overlapped axon and thereby taking over vacated territory (Gao and Macagno, 1987b; Gao, 1989). The death of an AP cell is therefore communicated to its homolog, but the mechanism underlying this signaling is presently unknown.

Growth cone "collapse" in vivo: are inhibitory interactions mediated by gap junctions?

In the leech embryo, oppositely directed axons of homologous anterior pagoda (AP) neurons overlap with each other extensively within the nerves that link adjacent ganglia, and inhibit each other's further growth (Gao and Macagno, 1987b). During this 5-8 d period of inhibition, the axons begin to grow thin, and eventually they retract completely. However, deletion of one overlapping AP cell results in the renewed growth of the remaining AP cell's axon, which then innervates territory vacated by the killed cell.

The effects of postsynaptic levels of cyclic AMP on excitatory and inhibitory responses of an identified central neuron.

The effects of cAMP on Mauthner (M-) cell excitatory and inhibitory responses were studied in vivo. Cyclic AMP was iontophoresed into the M-cell lateral dendrite, after which we monitored the changes in cellular responsiveness to stimulation of 2 classes of identified presynaptic cells: (1) excitatory fibers from the posterior branch of the ipsilateral eighth cranial nerve and (2) inhibitory interneurons activated by the M-cell collateral and commissural networks. We found that postsynaptic injections of cAMP increased the magnitudes of the electrically and chemically mediated EPSPs from the eighth nerve and enhanced M-cell inhibitory responses as well.