On the quantal hypothesis of neurotransmitter release: an explanation for the calcium dependence of the binomial parameters

Results for quantal neurotransmitter release can be explained by assuming a binomial distribution with a population of N elements each with a probability p to release a quantum in a given trial. The binomial parameter N was unexpectedly observed to depend on external calcium concentration and (to a lesser extent) on the frequency of stimulation. This observation is explained here by the hypothesis that the release population is not homogeneous. It is shown that the same hypothesis can also account for other experimental findings. A possible cause for this inhomogeneity is suggested.     

Prolonged Intracellular Na+ Dynamics Govern Electrical Activity in Accessory Olfactory Bulb Mitral Cells

Persistent activity has been reported in many brain areas and is hypothesized to mediate working memory and emotional brain states and to rely upon network or biophysical feedback. Here, we demonstrate a novel mechanism by which persistent neuronal activity can be generated without feedback, relying instead on the slow removal of Na⁺ from neurons following bursts of activity. We show that mitral cells in the accessory olfactory bulb (AOB), which plays a major role in mammalian social behavior, may respond to a brief sensory stimulation with persistent firing. By combining electrical recordings, Ca²⁺ and Na⁺ imaging, and realistic computational modeling, we explored the mechanisms underlying the persistent activity in AOB mitral cells. We found that the exceptionally slow inward current that underlies this activity is governed by prolonged dynamics of intracellular Na⁺ ([Na⁺]_i), which affects neuronal electrical activity via several pathways. Specifically, elevated dendritic [Na⁺]_i reverses the Na⁺-Ca²⁺ exchanger activity, thus modifying the [Ca²⁺]_i set-point. This process, which relies on ubiquitous membrane mechanisms, is likely to play a role in other neuronal types in various brain regions.     

Digital PCR-Based Method for Detecting CDKN2A Loss in Brain Tumours

Molecular Diagnosis & Therapy - CDKN2A is a key tumour suppressor gene and loss of CDKN2A can be found in many tumours. In astrocytoma grade IV, CDKN2A is deleted in more than 50% of tumours....     

Monitoring of effector and target cell stimulation during conjugation by fluorescence polarization

The aim of the present study was to trace early intracellular changes induced in effector and target cells during their conjugation. This was performed by monitoring the intracellular fluorescein fluorescence polarization (IFFP), using the Cellscan apparatus. This apparatus permits the repetitive spectroscopic measurement of individual selected live cells within a population of many cells, while the location of each cell is known and preserved during the various cell manipulations and/or their suspending medium. Both natural killer (NK) and lymphocyte activated killer (LAK) cells were used as effector cells, while NK-sensitive K562 and NK-resistant Daudi cell lines were used as targets. In this study kinetic IFFP measurements were carried out for a period of approximately 4 h following cell attachment. Within minutes following effector-target conjugation, transient reduction of IFFP was observed consecutively, first in the effector and then in the target cells. A continuous reduction of IFFP occurring only in target cells was also found 50 min following conjugation. No reduction in IFFP was observed using NK- and LAK-resistant target cells. Good correlation was found between early stages of conjugation, as assessed by IFFP, and cytolytic efficiency as assessed by ⁵¹chromium release assay. When NK-resistant and LAK-resistant target cells were used, no reduction of IFFP was observed.     

Variable nonspecific immunopotentiating efficacy of two preparations of MER

Summary Two preparations of MER, both originating from the same master lot held and distributed by the US National Cancer Institute, were assayed for ability to heighten the contact hypersensitivity response of mice to specific sensitization with dinitrofluorobenzene (DNFB). One preparation, obtained as a ready, formulated suspension for clinical use, failed consistently to potentiate reactivity. The other, supplied as the parent dry powder and brought into suspension in our laboratories with the same diluent, proved significantly efficacious under identical conditions of DNFB sensitization and testing.