53 research outputs found

    Action Potential Gating of Calcium Channels and Transmitter Release

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    The regulation of transmitter release at the neuromuscular junction is tightly regulated by the influx of calcium in the presynaptic nerve terminal. Interestingly, the probability that release sites at the neuromuscular junction will liberate transmitter during each action potential is very low. The reasons for this low probability of release are not well understood. To test the hypothesis that individual N-type calcium channels open with a low probability, single channel recordings of N-type voltage-gated calcium channels were performed. Using this approach I determined the conductance of these channels, their probability of gating during an action potential waveform, and the magnitude of calcium flux during a single channel opening. I conclude from these studies that N-type voltage-gated calcium channels have a very low probability of opening (< 5%) during an action potential and the characteristics of calcium entry during single channel openings can help to explain the low probability of transmitter release at release sites in the neuromuscular junction. To understand how calcium current is activated physiologically, the activation and resulting current from N-type calcium channels elicited by different action potential waveforms were studied. This work was carried out at both room temperature and 37°C to provide a physiological context. Using the whole-cell patch clamp techniques, I studied the activation of current during various action potential shapes and conditions, and the kinetics of N- and L-type current activation. Using this approach I determined that N-type channels activate more slowly than L-type. Furthermore, depending on the action potential shape used and the temperature, action potentials can activate varying proportions (I/Imax) of N-type calcium current (ranging from 10-100%). Under physiological conditions using a frog motoneuron action potential waveform I determined that there was a very low proportion of calcium current activated by a natural action potential (~32%). Adenosine 5´-triphosphate (ATP) is co-released with acetylcholine (ACh) at the neuromuscular junction, and has been found to inhibit transmission. I used the cutaneous pectoris muscle of the Rana pipiens to study ATP-mediated modulation of ACh release. Intracellular postsynaptic recordings were used as a measure of ACh release, and agents that perturb the ATP signaling were examined

    Copy Number Variation in Intron 1 of SOX5 Causes the Pea-comb Phenotype in Chickens

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    Pea-comb is a dominant mutation in chickens that drastically reduces the size of the comb and wattles. It is an adaptive trait in cold climates as it reduces heat loss and makes the chicken less susceptible to frost lesions. Here we report that Pea-comb is caused by a massive amplification of a duplicated sequence located near evolutionary conserved non-coding sequences in intron 1 of the gene encoding the SOX5 transcription factor. This must be the causative mutation since all other polymorphisms associated with the Pea-comb allele were excluded by genetic analysis. SOX5 controls cell fate and differentiation and is essential for skeletal development, chondrocyte differentiation, and extracellular matrix production. Immunostaining in early embryos demonstrated that Pea-comb is associated with ectopic expression of SOX5 in mesenchymal cells located just beneath the surface ectoderm where the comb and wattles will subsequently develop. The results imply that the duplication expansion interferes with the regulation of SOX5 expression during the differentiation of cells crucial for the development of comb and wattles. The study provides novel insight into the nature of mutations that contribute to phenotypic evolution and is the first description of a spontaneous and fully viable mutation in this developmentally important gene

    Effect of Audiovisual Training on Monaural Spatial Hearing in Horizontal Plane

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    The article aims to test the hypothesis that audiovisual integration can improve spatial hearing in monaural conditions when interaural difference cues are not available. We trained one group of subjects with an audiovisual task, where a flash was presented in parallel with the sound and another group in an auditory task, where only sound from different spatial locations was presented. To check whether the observed audiovisual effect was similar to feedback, the third group was trained using the visual feedback paradigm. Training sessions were administered once per day, for 5 days. The performance level in each group was compared for auditory only stimulation on the first and the last day of practice. Improvement after audiovisual training was several times higher than after auditory practice. The group trained with visual feedback demonstrated a different effect of training with the improvement smaller than the group with audiovisual training. We conclude that cross-modal facilitation is highly important to improve spatial hearing in monaural conditions and may be applied to the rehabilitation of patients with unilateral deafness and after unilateral cochlear implantation

    when history teaching turns into parrhesia the case of italian colonial crimes

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    The aim of this chapter was to highlight the importance and the consequentiality of a specific kind of history education that happens when teachers decide to openly narrate to their students the crimes committed by previous generations of their own group—crimes so far kept silenced and literally denied in the general social discourse. According to Foucault's categorization of different kinds of truth's speaking, we propose to call parrhesia this history teaching. After reviewing theoretical stances on consequences expected for young people receiving this kind of history education, empirical evidence is discussed referring to recent researches conducted on chosen case studies. Data suggest that knowledge conveyed by parrhesiastic historical teaching on previously silenced ingroup crimes allow young students to morally distance themselves from wrongdoings of older generations

    Tempo and Mode in Evolution of Transcriptional Regulation

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    Perennial questions of evolutionary biology can be applied to gene regulatory systems using the abundance of experimental data addressing gene regulation in a comparative context. What is the tempo (frequency, rate) and mode (way, mechanism) of transcriptional regulatory evolution? Here we synthesize the results of 230 experiments performed on insects and nematodes in which regulatory DNA from one species was used to drive gene expression in another species. General principles of regulatory evolution emerge. Gene regulatory evolution is widespread and accumulates with genetic divergence in both insects and nematodes. Divergence in cis is more common than divergence in trans. Coevolution between cis and trans shows a particular increase over greater evolutionary timespans, especially in sex-specific gene regulation. Despite these generalities, the evolution of gene regulation is gene- and taxon-specific. The congruence of these conclusions with evidence from other types of experiments suggests that general principles are discoverable, and a unified view of the tempo and mode of regulatory evolution may be achievable

    Common envelope evolution: where we stand and how we can move forward

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    Contains fulltext : 111306.pdf (preprint version ) (Open Access
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