What makes species unique? The contribution of proteins with obscure features

BACKGROUND: Proteins with obscure features (POFs), which lack currently defined motifs or domains, represent between 18% and 38% of a typical eukaryotic proteome. To evaluate the contribution of this class of proteins to the diversity of eukaryotes, we performed a comparative analysis of the predicted proteomes derived from 10 different sequenced genomes, including budding and fission yeast, worm, fly, mosquito, Arabidopsis, rice, mouse, rat, and human. RESULTS: Only 1,650 protein groups were found to be conserved among these proteomes (BLAST E-value threshold of 10(-6)). Of these, only three were designated as POFs. Surprisingly, we found that, on average, 60% of the POFs identified in these 10 proteomes (44,236 in total) were species specific. In contrast, only 7.5% of the proteins with defined features (PDFs) were species specific (17,554 in total). As a group, POFs appear similar to PDFs in their relative contribution to biological functions, as indicated by their expression, participation in protein-protein interactions and association with mutant phenotypes. However, POF have more predicted disordered structure than PDFs, implying that they may exhibit preferential involvement in species-specific regulatory and signaling networks. CONCLUSION: Because the majority of eukaryotic POFs are not well conserved, and by definition do not have defined domains or motifs upon which to formulate a functional working hypothesis, understanding their biochemical and biological functions will require species-specific investigations

Dose- and rate-dependent effects of cocaine on striatal neurons related to licking

To examine the role of striatal mechanisms in cocaine-induced stereotyped licking, the activity of lick-related neurons in the ventrolateral striatum of awake, freely moving rats engaged in licking was recorded before and after cocaine administration (0, 5, 10 and 20 mg/kg). Relative to zero dose, cocaine reduced lick duration and increased interlick interval, particularly at the high dose, but did not affect licking rhythm. Stereotyped licking was induced only by the high dose, evident by an increase in the number of licks in the absence of water delivery. Firing rates (FR) of striatal neurons phasically related to licking were compared between matched licks before and after injection, minimizing any influence of sensorimotor variables on changes in firing. Both increases and decreases in average FR were observed post-drug, exhibiting a dose-dependent pattern that strongly depended on pre-drug FR. At the middle and high doses relative to the zero dose group, the average FR of slow firing neurons were increased by cocaine, resulting from a general elevation of movement-related FR. By contrast, fast firing neurons showed decreased average FR only in the high dose group, with reduced FR across the entire range for these neurons. Additionally, without any drug present (prior to drug injection) FR were positively related to the strength of the correlation of FR with lick duration. Changes in behavioral correlations were demonstrated over time with no drug present (for slow firing neurons), and following cocaine administration (for slow firing neurons at all doses, and for fast firing neurons only at the high dose). Thus, differences were observed between slow and fast firing neurons in drug effects on FR, in the strength of their behavioral correlations and with respect to changes in their behavioral correlations, suggesting that fast firing neurons may be more strongly involved in the processing of movement parameters. These findings suggest that at the high dose, increased phasic activity of slow firing striatal neurons and simultaneously reduced phasic activity of fast firing striatal neurons may contribute, respectively, to the continual initiation of stereotypic movements and the absence of longer, more global movements.Ph.D.Includes bibliographical references (p. 96-106)

Dose- and Rate-Dependent Effects of Cocaine on Striatal Firing Related to Licking

To examine the role of striatal mechanisms in cocaine-induced stereotyped licking, we investigated the acute effects of cocaine on striatal neurons in awake, freely moving rats before and after cocaine administration (0, 5, 10, or 20 mg/kg). Stereotyped licking was induced only by the high dose. Relative to control (saline), cocaine reduced lick duration and concurrently increased interlick interval, particularly at the high dose, but it did not affect licking rhythm. Firing rates of striatal neurons phasically related to licking movements were compared between matched licks before and after injection, minimizing any influence of sensorimotor variables on changes in firing. Both increases and decreases in average firing rate of striatal neurons were observed after cocaine injection,and these changes exhibited a dose-dependent pattern that strongly depended on predrug firing rate. At the middle and high doses relative to the saline group, the average firing rates of slow firing neurons were increased by cocaine, resulting from a general elevation of movement-related firing rates. In contrast, fast firing neurons showed decreased average firing rates only in the high-dose group, with reduced firing rates across the entire range for these neurons. Our findings suggest that at the high dose, increased phasic activity of slow firing striatal neurons and simultaneously reduced phasic activity of fast firing striatal neurons may contribute, respectively, to the continual initiation of stereotypic movements and the absence of longer movements

Dose- and Rate-Dependent Effects of Cocaine on Striatal Firing Related to Licking

To examine the role of striatal mechanisms in cocaine-induced stereotyped licking, we investigated the acute effects of cocaine on striatal neurons in awake, freely moving rats before and after cocaine administration (0, 5, 10, or 20 mg/kg). Stereotyped licking was induced only by the high dose. Relative to control (saline), cocaine reduced lick duration and concurrently increased interlick interval, particularly at the high dose, but it did not affect licking rhythm. Firing rates of striatal neurons phasically related to licking movements were compared between matched licks before and after injection, minimizing any influence of sensorimotor variables on changes in firing. Both increases and decreases in average firing rate of striatal neurons were observed after cocaine injection,and these changes exhibited a dose-dependent pattern that strongly depended on predrug firing rate. At the middle and high doses relative to the saline group, the average firing rates of slow firing neurons were increased by cocaine, resulting from a general elevation of movement-related firing rates. In contrast, fast firing neurons showed decreased average firing rates only in the high-dose group, with reduced firing rates across the entire range for these neurons. Our findings suggest that at the high dose, increased phasic activity of slow firing striatal neurons and simultaneously reduced phasic activity of fast firing striatal neurons may contribute, respectively, to the continual initiation of stereotypic movements and the absence of longer movements