4 resultados para Works in Progress

em National Center for Biotechnology Information - NCBI


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This paper argues that historical works in pharmacy are important tools for the clinician as well as the historian. With this as its operative premise, delineating the tripartite aspects of pharmacy as a business enterprise, a science, and a profession provides a conceptual framework for primary and secondary resource collecting. A brief history and guide to those materials most essential to a historical collection in pharmacy follows. Issues such as availability and cost are discussed and summarized in checklist form. In addition, a glossary of important terms is provided as well as a list of all the major U.S. dispensatories and their various editions. This paper is intended to serve as a resource for those interested in collecting historical materials in pharmacy and pharmaco-therapeutics as well as provide a history that gives context to these classics in the field. This should provide a rationale for selective retrospective collection development in pharmacy.

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Recent studies show that neuronal mechanisms for learning and memory both dynamically modulate and permanently alter the representations of visual stimuli in the adult monkey cortex. Three commonly observed neuronal effects in memory-demanding tasks are repetition suppression, enhancement, and delay activity. In repetition suppression, repeated experience with the same visual stimulus leads to both short- and long-term suppression of neuronal responses in subpopulations of visual neurons. Enhancement works in an opposite fashion, in that neuronal responses are enhanced for objects with learned behavioral relevance. Delay activity is found in tasks in which animals are required to actively hold specific information “on-line” for short periods. Repetition suppression appears to be an intrinsic property of visual cortical areas such as inferior temporal cortex and is thought to be important for perceptual learning and priming. By contrast, enhancement and delay activity may depend on feedback to temporal cortex from prefrontal cortex and are thought to be important for working memory. All of these mnemonic effects on neuronal responses bias the competitive interactions that take place between stimulus representations in the cortex when there is more than one stimulus in the visual field. As a result, memory will often determine the winner of these competitions and, thus, will determine which stimulus is attended.

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The F1F0 ATP synthase is the smallest motor enzyme known. Previous studies had established that the central stalk, made of the γ and ɛ subunits in the F1 part and c subunit ring in the F0 part, rotates relative to a stator composed of α3β3δab2 during ATP hydrolysis and synthesis. How this rotation is regulated has been less clear. Here, we show that the ɛ subunit plays a key role by acting as a switch of this motor. Two different arrangements of the ɛ subunit have been visualized recently. The first has been observed in beef heart mitochondrial F1-ATPase where the C-terminal portion is arranged as a two-α-helix hairpin structure that extends away from the α3β3 region, and toward the position of the c subunit ring in the intact F1F0. The second arrangement was observed in a structure determination of a complex of the γ and ɛ subunits of the Escherichia coli F1-ATPase. In this, the two C-terminal helices are apart and extend along the γ to interact with the α and β subunits in the intact complex. We have been able to trap these two arrangements by cross-linking after introducing appropriate Cys residues in E. coli F1F0, confirming that both conformations of the ɛ subunit exist in the enzyme complex. With the C-terminal domain of ɛ toward the F0, ATP hydrolysis is activated, but the enzyme is fully coupled in both ATP hydrolysis and synthesis. With the C-terminal domain toward the F1 part, ATP hydrolysis is inhibited and yet the enzyme is fully functional in ATP synthesis; i.e., it works in one direction only. These results help explain the inhibitory action of the ɛ subunit in the F1F0 complex and argue for a ratchet function of this subunit.

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Mechanical injury to the adult mammalian spinal cord results in permanent morphological disintegration including severance/laceration of brain-cord axons at the lesion site. We report here that some of the structural consequences of injury can be averted by altering the cellular components of the lesion site with x-irradiation. We observed that localized irradiation of the unilaterally transected adult rat spinal cord when delivered during a defined time-window (third week) postinjury prevented cavitation, enabled establishment of structural integrity, and resulted in regrowth of severed corticospinal axons through the lesion site and into the distal stump. In addition, we examined the natural course of degeneration and cavitation at the site of lesion with time after injury, noting that through the third week postinjury recovery processes are in progress and only at the fourth week do the destructive processes take over. Our data suggest that the adult mammalian spinal cord has innate mechanisms required for recovery from injury and that timed intervention in certain cellular events by x-irradiation prevents the onset of degeneration and thus enables structural regenerative processes to proceed unhindered. We postulate that a radiation-sensitive subgroup of cells triggers the delayed degenerative processes. The identity of these intrusive cells and the mechanisms for triggering tissue degeneration are still unknown.