How many numbers are required to specify sequence-dependent properties of polynucleotides?

There are 10 unique dinucleotides of double-stranded DNA, but only 8 independent nearest-neighbor energies that occur in circular DNA, as shown by D. M. Gray and I. Tinoco [(1970) Biopolymers 9, 223-244]. We extend that analysis to include end effects, and show that the number of unique dinucleotide pairs (including ends) is 14, but there are only 12 independent energies. We discuss how these 12 energies (or spectra or any other pairwise additive property) can be measured and displayed, and how they should and should not be compared between experimenters. As an example, we analyzed the recently reported melting curves [M.J. Doktycz et al. (1992) Biopolymers, 32, 849-864.] of 16 DNA dumbbells in two different Na+ environments. This analysis reveals a new means for evaluating end effects and the emergence of longer than nearest-neighbor interactions at low salt concentration.     

Biologically active analogs of thymopentin with enhanced enzymatic stability

Thymopentin, a synthetic pentapeptide fragment of thymopoietin (residues 32–36, Arg-Lys-Asp-Val-Tyr) is biologically active but susceptible to proteolytic digestion. Analogs were synthesized and studied for biological activity and susceptibility to peptidases. Amino acid changes were incorporated at positions known to not affect activity adversely and N-terminal acetylation and C-terminal amidation were used to increase resistance to proteolytic degradation by exopeptidases. Ac-Pro²-TP5-NH₂ and Aib²-TP5-NH₂ retained activity and were shown to exhibit a high degree of stability when incubated in human serum.     

Bicarbonate-induced synthesis of polysaccharide during morphogenesis by synchronous,single-generations of blastocladiella emersonii

Summary Relative to the formation of an ordinary colorless plant of Blastocladiella emersonii (which does not require bicarbonate for its formation), the bicarbonate-induced genesis of a resistant-sporangial plant (R.S.) is associated with: (a), a two-fold increase in the rate of exponential, net synthesis of an endogenous, apparently highly branched, glycogen-like polysaccharide; and (b), a three-fold increase in the total pool of this polysaccharide built up within the plant.The polysaccharide accumulates during the early development of an R. S. plant in synchronous, single-generation culture when glucose is being consumed rapidly from the medium without detectable production of lactic acid.The accumulated polysaccharide pool disappears again during the maturation period of a resistant-sporangial plant, when glucose is no longer being consumed from the medium. During this time, (a), approximately one mole of lactic acid is liberated per mole of polysaccharideglucose consumed; and (b), the specific activity of glucose-6-phosphate dehydrogenase rises sharply. These observations are consistent with the possibility that the final maturation of the resistant sporangium is associated with an increase in glucose metabolism via the hexose monophosphate shunt.     

A distinct African lentivirus from Sykes' monkeys.

Asymptomatic infection with simian immunodeficiency virus (SIV) has been demonstrated in African Sykes' monkeys (Cercopithecus mitis albogularis), and virus isolation confirmed infection with a novel SIV from Sykes' monkeys (SIVsyk). Macaques inoculated with SIVsyk became persistently infected but remained clinically healthy. We utilized polymerase chain reaction amplification to generate a full-length, infectious molecular clone of SIVsyk. The genome organization of SIVsyk is similar to that of the other primate lentiviruses, consisting of gag, pol, vif, vpr, tat, rev, env, and nef. A unique feature is the absence of the highly conserved NF-kappa B binding site in the long terminal repeat. SIVsyk is genetically equidistant from other primate lentiviruses. Thus, SIVsyk represents a new group that is distinct from the four previously recognized primate lentivirus groups: human immunodeficiency virus type 1 (HIV-1), SIV from sooty mangabeys (SIVsmm) and HIV-2, SIV from African green monkeys (SIVagm), and SIV from mandrills (SIVmnd). The genetic differences between SIVsyk and SIVagm, isolates derived from monkeys of the same genus, underscore the potential for other distinct SIVs which have yet to be isolated and characterized.     

Osmoregulatory responses of glaucous-winged gulls (Larus glaucescens) to dehydration and hemorrhage

The effects of dehydration and hemorrhage on plasma ionic, osmotic, and antidiuretic hormone (arginine vasotocin) concentrations and of hemorrhage on salt gland secretion and glomerular filtration rate were evaluated in glaucous-winged gulls, Larus glaucescens. Dehydration for 24 h did not affect plasma ionic, osmotic or arginine vasotocin concentrations; 72 h dehydration significantly elevated plasma osmolality, plasma sodium and chloride concentrations, and plasma arginine vasotocin concentration, but did not affect plasma potassium concentration. Constant infusion of 0.8 mol·l^-1 NaCl increased plasma arginine vasotocin concentration and produced salt gland secretion in seven gulls; four secreted well, while three secreted less well. Removal of 20% blood volume during saline infusion immediately reduced (P<0.001) salt gland secretion rate in all gulls. After bleeding, good secretors maintained glomerular filtration rate and urine flow rate; the poorer secretors increased glomerular filtration rate and became diuretic. Blood replacement returned salt gland secretion rate to the prebleeding level (P<0.05) without affecting salt gland secretions sodium concentration in gulls which secreted well, but did not restimulate salt gland secretion in gulls which secreted poorly. Reinfusion of blood had no effect on glomerular filtration rate. Bleeding and blood replacement did not affect plasma arginine vasotocin concentration.Abbreviations AVT arginine vasotocin - ECF extracellular fluid - ECFV extracellular fluid volume - EDTA ethylenediaminetetra-acetate - EWL evaporative water loss - GFR glomerular filtration rate - Hct hematocrit - LB large blood sample - [Na⁺]_pl plasma sodium concentration - Osm_pl plasma osmolality - PEG polyethylene glycol - RH relative humidity - RIA radioimmunoassay - SB small blood sample - SGS salt gland secretion - T _a ambient temperature - TFA trifluoroacetic acid - UFR urine flow rate     

Progression of heart failure: A role for interstitial fibrosis

Progressive deterioration of left ventricular (LV) function is a characteristic feature of the heart failure (HF) state. The mechanism or mechanisms responsible for this hemodynamic deterioration are not known but may be related to progressive intrinsic dysfunction, degeneration and loss of viable cardiocytes. In the present study, we tested the hypothesis that accumulation of collagen in the cardiac interstitium (reactive interstitial fibrosis, RIF), known to occur in HF, results in reduced capillary density (CD=capillary/fiber ratio) and increased oxygen diffusion distance (ODD) which can lead to hypoxia and dysfunction of the collagen encircled myocyte. Studies were performed in LV tissue obtained from 10 dogs with chronic HF (LV ejection fraction 26±1%) produced by multiple sequential intracoronary, microembolizations. In each dog, CD and ODD were evaluated in LV regions that manifested severe RIF (volume fraction 16±2%) and in LV regions of little or no RIF (volume fraction 4±1%). In regions of severe RIF, CD was significantly decreased compared to regions of no RIF (0.92±0.02 vs. 1.05±0.03) (P<0.03). Similarly, ODD was significantly increased in regions of severe RIF compared to regions of no RIF (15.3±0.4 vs. 12.2±0.3 m) (P<0.001). These data suggest that in dogs with chronic HF, constituent myocytes of LV regions which manifest severe RIF may be subjected to chronic hypoxia; a condition that can adversely impact the function and viability of the collagen encircled cardiocyte.     

Ventricular remodeling: insights from pharmacologic interventions with angiotensin-converting enzyme inhibitors

Structural remodeling of the left ventricular (LV) myocardium develops in a time-dependent fashion following acute myocardial infarction and may be an integral component in the transition toward overt heart failure. Globally, the remodeling process is characterized by progressive LV enlargement and increased chamber sphericity. At the cellular level, the remodeling process is associated with myocyte slippage, hypertrophy, and accumulation of collagen in the interstitial compartment. In the present study, we examined the effects of early, long-term monotherapy with the angiotensin converting enzyme (ACE) inhibitor, enalapril, on the progression of LV remodeling in dogs with LV dysfunction (ejection fractions 30–40%) produced by multiple sequential intracoronary microembolizations. Dogs were randomized to 3 months oral therapy with enalapril (n=7) or to no treatment (n=7). In untreated dogs, LV end-systolic volume index (ESVI), end-diastolic volume index (EDVI) and chamber sphericity increased significantly during the 3 months follow-up period. In contrast, in dogs treated with enalapril ESVI, EDVI and chamber sphericity remained essentially unchanged. Treatment with enalapril attenuated myocyte hypertrophy and the accumulation of interstitial collagen in comparison to untreated dogs. These data indicate that early treatment with ACE inhibitors can prevent the progression of LV remodeling in dogs with LV dysfunction. Afterload reduction, inhibition of direct action of angiotensin-II and possibly the decrease in bradykinin degradation elicited by ACE inhibition may act in concert in preventing the progression LV chamber remodeling.     

Conformational analysis of pseudo-peptides: The case of FK888, a potent and selective substance P receptor antagonist

Molecular recognition is a central problem in medicinal sciences, and therefore a knowledge of the salient molecular features necessary for efficient interaction with a receptor as well as their relative spatial arrangement is of crucial importance. Thus, an insight into probable biorelevant 3D structures by conformational analysis is equally fundamental. In the present study, we describe the conformational analysis of FK888, a potent and selective pseudo-peptide antagonist of the NK₁ receptor of substance P, using an in-house developed method (CONFEX: CONFormational EXploration). Conformations could be subdivided into four families according to peptidic folding: the first two present an extended conformation which can be characterized as a hairpin-like structure, while the other two present a -turn-like arrangement. These results were compared with experimental findings obtained by NMR spectroscopy.     

Morphological and physiological responses of Scaevola sericea (Goodeniaceae) seedlings to salt spray and substrate salinity

The effects of substrate salinity and salt spray upon seedlings of Scaevola sericea were examined in this study. Three levels of substrate salinity: 0.0 ppt, 3.0 ppt, and 10.0 ppt were examined in conjunction with three levels of salt spray: zero, medium (200 mg m^-2mdd^-1), and high (1200–1500 mg-m^-2mdd^-1). Leaf surface area, root to shoot ratio, as well as leaf, stem, and root mass decreased significantly (P 0.05) with increasing substrate salinity. Biomass accumulation was very low at 10.0 ppt substrate salinity, suggesting that higher levels of substrate salinity cannot be tolerated by the seedlings. Salt spray had a substantial effect on several of these variables, however its effects were less pronounced than those of substrate salinity. Cell sap osmolarity, leaf thickness, and leaf specific mass increased significantly (P 0.05) with both increasing substrate salinity and salt spray levels. Leaf carbon isotope ratios (δ^l3C) became more positive with increasing salinity, indicating an enhancement of the intrinsic water use efficiency of the seedlings at higher salinities. Scaevola sericea is one of the dominant plants found at the leading edge of strand communities in the Hawaiian archipelago and throughout much of the tropical Pacific. Since substrate salinity and salt spray increase with proximity to the ocean, the two factors may act together to limit the seaward expansion of S. sericea in coastal habitats.