Circadian rhythm of plasma sodium is disrupted in spontaneously hypertensive rats fed a high-NaCl diet

High-NaCl diets elevate arterial pressure in NaCl-sensitive individuals, and increases in plasma sodium may trigger this effect. The present study tests the hypotheses that 1) plasma sodium displays a circadian rhythm in rats, 2) the plasma sodium rhythm is disturbed in spontaneously hypertensive rats (SHR), and 3) excess dietary NaCl elevates plasma sodium concentration in SHR. The results demonstrate that plasma sodium has a circadian rhythm that is inversely related to the circadian rhythm of arterial pressure. Although the plasma sodium rhythms of SHR and control rats are nearly identical, the plasma sodium concentrations are significantly higher in SHR throughout the 24-h cycle. Maintenance on a high-NaCl diet increases plasma sodium concentration similarly in both SHR and control rats, but it blunts the plasma sodium rhythm only in SHR. These results demonstrate that in rats, plasma sodium has a circadian rhythm and that high-NaCl diets increase plasma sodium concentration.     

Fused bicyclic Gly-Asp beta-turn mimics with potent affinity for GPIIb-IIIa. Exploration of the arginine isostere

6-[4-Amidinobenzoyl]amino]-tetralone-2-acetic acid is a potent antagonist of GPIIb-IIIa. Substitution in the meta position of the benzamidine, or replacement with a heteroaryl amidine was tolerated in this series. Use of an acyl-linked 4-alkyl piperidine as an arginine isostere also provided active compounds. Compounds from this series provided substantial systemic exposure in the rat following oral administration.     

An AFLP-based genetic linkage map of Plasmodium chabaudi chabaudi

Background

Plasmodium chabaudi chabaudi can be considered as a rodent model of human malaria parasites in the genetic analysis of important characters such as drug resistance and immunity. Despite the availability of some genome sequence data, an extensive genetic linkage map is needed for mapping the genes involved in certain traits.

Methods

The inheritance of 672 Amplified Fragment Length Polymorphism (AFLP) markers from two parental clones (AS and AJ) of P. c. chabaudi was determined in 28 independent recombinant progeny clones. These, AFLP markers and 42 previously mapped Restriction Fragment Length Polymorphism (RFLP) markers (used as chromosomal anchors) were organized into linkage groups using Map Manager software.

Results

614 AFLP markers formed linkage groups assigned to 10 of 14 chromosomes, and 12 other linkage groups not assigned to known chromosomes. The genetic length of the genome was estimated to be about 1676 centiMorgans (cM). The mean map unit size was estimated to be 13.7 kb/cM. This was slightly less then previous estimates for the human malaria parasite, Plasmodium falciparum

Conclusion

The P. c. chabaudi genetic linkage map presented here is the most extensive and highly resolved so far available for this species. It can be used in conjunction with the genome databases of P. c chabaudi, P. falciparum and Plasmodium yoelii to identify genes underlying important phenotypes such as drug resistance and strain-specific immunity.     

The highly conserved C-terminal dileucine motif in the cytosolic domain of the human immunodeficiency virus type 1 envelope glycoprotein is critical for its association with the AP-1 clathrin adaptor [correction of adapter

Short amino acid sequences in the cytosolic domains of transmembrane proteins are recognized by specialized adaptor [corrected] proteins which are part of coated vesicles utilized to transport membrane proteins between the trans-Golgi network (TGN) and the plasma membrane (forward and backward). Previously, we and others reported that the membrane-proximal tyrosine residues Y712 (human immunodeficiency virus [HIV]) and Y721 (simian immunodeficiency virus [SIV]) in the envelope glycoprotein (Env) of the primate lentiviruses are crucial for the association of Env with clathrin-associated adaptor [corrected] complex AP-2. The same tyrosine-based endocytosis motifs in the cytosolic domains (EnvCD) of transmembrane gp41 of HIV type 1 (HIV-1) and SIV, respectively, were also shown to modulate the interaction with TGN- and endosome-based clathrin-associated complex AP-1. Our findings suggested that EnvCD binding to AP-1, unlike the association of EnvCD with AP-2, is dependent largely on residues other than Y712 and Y721. Here, we tested if motifs downstream of Y712 affect HIV-1 EnvCD-AP-1 binding and Env trafficking. Mutational analysis revealed that the C-terminal leucine-based motif in Env was crucial for the recruitment of AP-1 in vitro and in Env-expressing cells. In addition to affecting Env-AP-1 association, mutations at the C terminus of Env also altered the subcellular localization of Env, suggesting that proper post-Golgi routing of Env depends on its recruitment of AP-1. Finally, the C-terminal dileucine was shown to assist the membrane-proximal Y712 motif in restricting the cell surface expression of Env.     

Synthesis and characterization of thermoset biodegradable elastomers based on star-poly(epsilon-caprolactone-co-D,L-lactide)

Biodegradable elastomers represent a useful class of biomaterials. In this paper, we synthesize thermoset elastomers by utilizing the living nature of ring-opening polymerization of a star copolymer of D,L-lactide and epsilon-caprolactone initiated with glycerol and catalyzed by stannous 2-ethylhexanoate. The star copolymers were synthesized of varying molecular weight and monomer composition and cross-linked by compression molding using a dilactone, bis(epsilon-caprolactone-4-yl)propane dissolved in epsilon-caprolactone monomer. The elastomers were then characterized by differential scanning calorimetry and uniaxial tensile testing and their physical properties related to the nature of the star copolymer prepolymers. The results demonstrate a means of predictably altering the elastomer physical properties by adjusting the star copolymer prepolymer initial molecular weight and monomer ratio.     

Effects of L-carnitine administration on VO2max and the aerobic-anaerobic threshold in normoxia and acute hypoxia

Seven healthy young male adults were subjected to a total of 56 tests to ascertain the effects of L-carnitine (L-C) and a placebo (P) on ventilation, O2 intake (VO2), CO2 output, heart rate, blood pressure and serum lactic acid, non-esterified fatty acid, glycerol and glucose during strenuous and aerobic/anaerobic threshold-level treadmill exercise. The tests were made in conditions of normoxia (O2 = 20.9%) and hypoxia (O2 = 13.0%, equivalent to 3,500 m above sea level). The only clear difference was in the respiratory quotient (RQ = 0.883, SD 0.025 vs 0.904, SD 0.035) after L-C and P administration respectively (P less than 0.01), under normal oxygenation and 0.861, SD 0.052 following L-C vs 0.926, SD 0.040 after P (P less than 0.01) in acute hypoxia at VO2 levels around the anaerobic threshold. The lower RQ values of the L-C-treated subjects during hypoxia indicate a lower rate of carbohydrate transformation.     

New Chinchillid Rodents (Hystricognathi: Caviomorpha) from Northern Chile and Bolivia Fill a 17-Million-Year Gap in the Pan-Chinchilline Fossil Record

Journal of Mammalian Evolution - The fossil record of chinchillid rodents (Hystricomorpha: Caviomorpha) begins in the early Miocene. However, nearly all remains have thus far been limited to the...     

Accuracy of single-plane fluoroscopy in determining relative position and orientation of total knee replacement components

The accuracy of estimating the relative pose between knee replacement components, in terms of clinical motion, is important in the study of knee joint kinematics. The objective of this study was to determine the accuracy of the single-plane fluoroscopy method in calculating the relative pose between the femoral component and the tibial component, along knee motion axes, while the components were in motion relative to one another. The kinematics of total knee replacement components were determined in vitro using two simultaneous methods: single-plane fluoroscopic shape matching and an optoelectronic motion tracking system. The largest mean differences in relative pose between the two methods for any testing condition were 2.1°, 0.3°, and 1.1° in extension, abduction, and internal rotation respectively, and 1.3, 0.9, and 1.9 mm in anterior, distal, and lateral translations, respectively. For the optimized position of the components during dynamic trials, the limits of agreement, between which 95% of differences can be expected to fall, were -2.9 to 4.5° in flexion, -0.9 to 1.5° in abduction, -2.4 to 2.1° in external rotation, -2.0 to 3.9 mm in anterior-posterior translation, -2.2 to 0.4mm in distal-proximal translation and -7.2 to 8.6mm in medial-lateral translation. These mean accuracy values and limits of agreement can be used to determine whether the shape-matching approach using single-plane fluoroscopic images is sufficiently accurate for an intended motion tracking application.