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Biomedical subjects

M Salomon

Publications and source records attributed to M Salomon.

At least 37 records · Page 2Linked to original sources

Prediction of alpha-helices in proteins with the hydrophobic strip-of-helix template and distributions of other amino acids around the hydrophobic strip.

Upon addition of requirements for highly characteristic distributions of helix-stabilizing residues to an alpha-helix predictor based upon identification of a longitudinal, hydrophobic strip-of-helix pattern, maximal sensitivity and efficiency scores approached 50% levels at a high degree of stringency. The hydrophobic strip-of-helix template ([symbol: see text], joined in a circle) was applied to 247 helices to maximize the strip-of-helix hydrophobicity index (SOHHI; the mean hydrophobicity of residues in [symbol: see text] positions). Statistically significant increases or decreases in the frequencies of certain residues are observed in some [symbol: see text] and [symbol: see text] positions: [symbol: see text] in the helix (including N- and C-terminal [symbol: see text] in the helix): Leu, Ile, Val, Phe, and Met; first [symbol: see text] positions in extensions of the template to surrounding segments: not increased Leu, Ile, Val, Phe, or Met; N-terminal [symbol: see text]: Asp, Glu; C-terminal [symbol: see text] and the first [symbol: see text] after the helix: His, Lys, Arg; N-terminal [symbol: see text]: Asn; C-terminal [symbol: see text]: Gln; smallest residue in longitudinal strip-of-helix: Ala or Val at crossing points between helices. An algorithm was then derived to indicate alpha-helices by merging predictions with templates [symbol: see text] and [symbol: see text], where the SOHHI > or = 3.0 in the Kyte-Doolittle scale. Relative to the baseline prediction using only the template, more elaborate rules using combinations of other structural patterns produced more efficient (49 versus 42%, respectively) but less sensitive (32 versus 42%, respectively) predictions when the prediction was required to overlap substantially with the known helix. These maximal sensitivities and efficiencies imply that some helices may be formed in folding intermediates but are lost upon coalescence of the final form. Better predictions of protein structure from the primary sequence may require modeling of competing interactions of local structures in folding intermediates.

Amino Acids↗

Comparison of actual and random-positioning-model distributions of peptide scavenging and T cell-presented sites in antigenic proteins.

In a peptide with a T cell-presented epitope (T site), a folded structure with a hydrophobic surface, 'the scavenger (S) site', may regulate transfer to major histocompatibility complex class II molecules. Three procedures which were proposed to identify T sites selected for amphipathic helical patterns but not T sites. In testing whether S sites lay in or near T sites, we found their linkage was not greater than that generated by a model in which segments of equal length and number to the S and T sites for each protein were distributed at random. This study establishes criteria for evaluation of schemes to predict functional motifs in antigenic proteins.

Amino Acid Sequence↗

FMH-induced decrease in central histamine levels produces increased feeding and body weight in rats.

The present study tested the long-term effects of the histamine (H) synthesis inhibitor alpha-fluoromethylhistidine (FMH) on feeding and body weight in rats. FMH (administered via 2-week osmotic minipumps) increased feeding significantly throughout the test period. Body weights were also significantly increased toward the end of the test period. Hypothalamic H assays, performed at the end of the study, confirmed that FMH-treated rats had significantly lower H levels than controls. In general, the results suggest that H activity and feeding are inversely related.

Animals↗

Differential effects of psychotropic drugs on feeding in rats: is histamine blockade involved?

The present animal studies tested the hypothesis that drug-induced blockade of histamine-1 receptors leads to appetite stimulation. Test agents included the antipsychotic promazine which has very potent antihistaminic effects, as well as the antipsychotic haloperidol and the antidepressant desipramine which both have negligible antihistaminic effects. In support of the hypothesis, significant appetite stimulation occurred only with promazine, while the other two test agents did not increase feeding, and even produced some suppression in food intake.

Animals↗

Sequence analysis and protein import studies of an outer chloroplast envelope polypeptide.

A chloroplast outer envelope membrane protein was cloned and sequenced and from the sequence it was possible to deduce a polypeptide of 6.7 kDa. It has only one membrane-spanning region; the C terminus extends into the cytosol, whereas the N terminus is exposed to the space between the two envelope membranes. The protein was synthesized in an in vitro transcription-translation system to study its routing into isolated chloroplasts. The import studies revealed that the 6.7-kDa protein followed a different and heretofore undescribed translocation pathway in the respect that (i) it does not have a cleavable transit sequence, (ii) it does not require ATP hydrolysis for import, and (iii) protease-sensitive components that are responsible for recognition of precursor proteins destined for the inside of the chloroplasts are not involved in routing the 6.7-kDa polypeptide to the outer chloroplast envelope.

Amino Acid Sequence↗

Cloning and sequence analysis of cDNAs encoding the cytosolic precursors of subunits GapA and GapB of chloroplast glyceraldehyde-3-phosphate dehydrogenase from pea and spinach.

Chloroplast glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is composed of two different subunits, GapA and GapB. cDNA clones containing the entire coding sequences of the cytosolic precursors for GapA from pea and for GapB from pea and spinach have been identified, sequenced and the derived amino acid sequences have been compared to the corresponding sequences from tobacco, maize and mustard. These comparisons show that GapB differs from GapA in about 20% of its amino acid residues and by the presence of a flexible and negatively charged C-terminal extension, possibly responsible for the observed association of the enzyme with chloroplast envelopes in vitro. This C-terminal extension (29 or 30 residues) may be susceptible to proteolytic cleavage thereby leading to a conversion of chloroplast GAPDH isoenzyme I into isoenzyme II. Evolutionary rate comparisons at the amino acid sequence level show that chloroplast GapA and GapB evolve roughly two-fold slower than their cytosolic counterpart GapC. GapA and GapB transit peptides evolve about 10 times faster than the corresponding mature subunits. They are relatively long (68 and 83 residues for pea GapA and spinach GapB respectively) and share a similar amino acid framework with other chloroplast transit peptides.

Amino Acid Sequence↗

Rapid antidepressant response to alprazolam in depressed patients with high catecholamine output and heterologous desensitization of platelet adenylate cyclase.

The present study examined the relationship between 24-hr urinary catecholamine (norepinephrine and epinephrine) output and measures of platelet adenylate cyclase (AC) activity in depressed patients (n = 17) and control subjects (n = 10). In both groups, significant inverse correlations were observed when 24-hr urinary catecholamine levels were examined in relation to measures of both receptor-mediated (prostaglandin D2 and alpha 2-adrenergic) and postreceptor-mediated (NaF) platelet AC enzyme activities, suggesting that circulating catecholamines may regulate platelet AC by heterologous (agonist-nonspecific) desensitization of the AC enzyme complex. Depressed patients who had favorable antidepressant responses to alprazolam had significantly higher pretreatment urinary catecholamine output and lower receptor-mediated platelet AC enzyme activities than control subjects, whereas the nonresponders did not. After 8 days of treatment with alprazolam, urinary catecholamine levels declined significantly. In responders, receptor-mediated measures of platelet AC activity increased significantly by day 8 to values comparable to those in control subjects; but similar changes were not observed in nonresponders. Prior to treatment, responders showed a strict linear relationship between receptor-mediated (prostaglandin D2) and postreceptor-mediated (NaF) stimulation of platelet AC activity through the stimulatory guanine nucleotide regulatory protein (Ns), whereas nonresponders did not. This suggests the presence of two distinct coupling interactions between platelet prostaglandin D2 receptors and the stimulatory guanine nucleotide regulatory protein in responders and nonresponders to the antidepressant effects of alprazolam prior to treatment. The authors propose that catecholamines, possibly acting through prostaglandins, may regulate platelet AC enzyme activity by heterologous desensitization occurring through postreceptor mechanisms.

Adenylyl Cyclases↗