Boundary conditions at the cartilage-synovial fluid interface for joint lubrication and theoretical verifications

The objective of this study is to establish and verify the set of boundary conditions at the interface between a biphasic mixture (articular cartilage) and a Newtonian or non-Newtonian fluid (synovial fluid) such that a set of well-posed mathematical problems may be formulated to investigate joint lubrication problems. A "pseudo-no-slip" kinematic boundary condition is proposed based upon the principle that the conditions at the interface between mixtures or mixtures and fluids must reduce to those boundary conditions in single phase continuum mechanics. From this proposed kinematic boundary condition, and balances of mass, momentum and energy, the boundary conditions at the interface between a biphasic mixture and a Newtonian or non-Newtonian fluid are mathematically derived. Based upon these general results, the appropriate boundary conditions needed in modeling the cartilage-synovial fluid-cartilage lubrication problem are deduced. For two simple cases where a Newtonian viscous fluid is forced to flow (with imposed Couette or Poiseuille flow conditions) over a porous-permeable biphasic material of relatively low permeability, the well known empirical Taylor slip condition may be derived using matched asymptotic analysis of the boundary layer at the interface.     

Male reproductive success in harem troops of hanuman langurs (Presbytis entellus)

Based on cross-sectional and longitudinal data collected in 1967–1988 by various observers, male reproductive success was studied in the Hanuman langurs of Jodhpur, India. The harem-structured social organization ensures a high degree of paternity certainty. Births occur throughout the year, with significant peaks and minima in March and November, respectively (n =398).The interbirth interval averages 16.7 months (n = 114).The duration of harem residencies varies between 3 days and ≥ 74.0 months, with a mean of 26.5 (n = 64). Harem holder replacements occur during all months of the year. No male achieves residency in more than one troop, suggesting that residency is associated with a distinct peak in the resource holding potential of a given male. Reproductive success among males varies considerably. Male mortality is high due to migration and intrasexual competition, leading to an adult sex ratio of 1:4.9. It is estimated that one-quarter of all adult males will never gain harem residency. Conceptions achieved outside harem residencies are so rare (4.7%) that a viable low-risk strategy, opting for longevity instead of harem residency, is unlikely. Tenure length has a stronger influence on male reproductive success than harem size because interbirth intervals are significantly shorter in small harems than in larger ones. It is assumed that females in one-male breeding structures compete for sperm and that such competition is more intense in larger harems.     

TRH analog MK-771 reverses neurochemical and learning deficits in medial septal-lesioned rats

Microinjection of ibotenic acid into medial septum of rats decreased choline acetyltransferase (CAT) and high-affinity choline uptake (HACU) activities in hippocampus and retarded the learning of a spatial memory task in the radial-arm maze. Administration of MK-771, a stable TRH analog, to such animals restored HACU activity in hippocampus to normal levels. Daily treatment of rats with MK-771 prior to maze running also restored the animals' learning ability. MK-771 did not enhance hippocampal HACU activity or maze performance in sham-lesioned rats. These results suggest that MK-771 reversed the ibotenic acid-induced memory deficit by restoring septohippocampal cholinergic function. MK-771 and other TRH analogs may represent novel agents for improving memory deficits produced by cholinergic insufficiency in Alzheimer's disease.     

Disulfide and secondary structures of recombinant human granulocyte colony stimulating factor

Molecular characteristics and secondary structures of recombinant methionyl human granulocyte colony stimulating factor produced by genetically engineered Escherichia coli are described. Limited radiolabeling of the protein with tritiated iodoacetate and determination of the labeled residue revealed that this recombinant protein contains only one free cysteine at position 17 which is not essential for activity. The free cysteine is inaccessible to modification unless the molecule is unfolded under denaturing conditions. The molecule forms two disulfide bridges which were assigned as Cys(36)-Cys(42) and Cys(64)-Cys(74) based on the results of isolation and characterization of disulfide-containing peptides obtained from a subtilisin digest of the intact protein. CD analyses and secondary structure prediction suggest that the molecule is abundant in alpha-helical structures.     

Molecular dynamics of antitumor ether-linked phospholipids in model membranes: a spin-label study

We have synthesized a spin-labeled derivative of ET-18-OCH3, a known antitumor ether-linked phospholipid. The spin-labeled analog was shown to be as potent as ET-18-OCH3 in inhibiting 3H-thymidine uptake of HL60 leukemic cells. Electron spin resonance (ESR) studies showed that the mobility of this ether-linked phospholipid in the membrane is more restricted when compared to its ester-linked counterparts. It is probable that the absence of the bulky carbonyl oxygens allows closer packing of the two alkyl chains in the ether-linked phospholipid, thereby reducing the angular amplitude of the motion of the alkyl chains. These findings may be of importance in elucidating mechanisms by which the antitumor ether-linked phospholipids perturb the structure of cellular membranes.     

31P NMR spectra of ethidium, quinacrine, and daunomycin complexes with poly(adenylic acid).poly(uridylic acid) RNA duplex and calf thymus DNA

31P NMR provides a convenient monitor of the phosphate ester backbone conformational changes upon binding of the intercalating drugs ethidium, quinacrine, and daunomycin to sonicated poly(A).poly(U) and calf thymus DNA. 31P chemical shifts can also be used to assess differences in the duplex unwinding angles in the presence of the drug. Thus a new 31P signal, 1.8-2.2 ppm downfield from the double-stranded helix signals, is observed in the ethidium ion-poly(A).poly(U) complex. This signal arises from phosphates which are in perturbed environments due to intercalation of the drug. This is in keeping with the hypothesis that the P-O ester torsional angle in phosphates linking the intercalated base pairs is more trans-like. Similar though smaller deshielding of the 31P signals is observed in sonicated poly(A).poly(U)-quinacrine complexes as well as in the daunomycin complexes. The effect of added ethidium ion, quinacrine, and daunomycin on the 31P spectra of sonicated calf thymus DNA is consistent with Wilson and Jones' (1982) earlier study. In these drug-DNA complexes the drug produces a gradual downfield shift in the DNA 31P signal without the appearance of a separate downfield peak. These differences are attributed to differences in the rate of chemical exchange of the drug between free and bound duplex states. The previous correlation of 31P chemical shift with drug duplex unwinding angle (Wilson & Jones, 1982) is confirmed for both the RNA and DNA duplexes.     

Conformational changes of plasma fibronectin detected upon adsorption to solid substrates: a spin-label study

Changes in local environment of the free sulfhydryl groups in plasma fibronectin upon adsorption of the protein to polystyrene beads have been examined by electron spin resonance (ESR) spin-label spectroscopy. The two free sulfhydryl groups per subunit of plasma fibronectin were modified chemically with an [15N, 2H]maleimide spin-label. For soluble fibronectin, both free sulfhydryl groups are shown to be in confined environments as evidenced from the labeled protein exhibiting a strongly immobilized ESR spectrum as described previously using [14N, 1H]maleimide spin-labels [Lai, C.-S., & Tooney, N. M. (1984) Arch. Biochem. Biophys. 228, 465-473]. When the labeled protein was adsorbed to the beads, half of the strongly immobilized component was found to convert into a weakly immobilized component, a result indicating that one of the two labeled sites becomes exposed and exhibit a fast tumbling motion. Experiments conducted using various spin-labeled fibronectin fragments suggest that the newly exposed labeled site is located between the DNA-binding and the cell-binding regions of the molecule. The data obtained indicate that, upon adsorption to polystyrene beads, plasma fibronectin undergoes a conformational change through which the buried free sulfhydryl group near the cell-binding region of the molecule is exposed. This observation may have important implications regarding the expression of cell adhesive properties of the fibronectin molecule.