No Evidence for a Y Chromosomal Effect on Alternative Behavioral Strategies in Mice

This study takes the first step toward testing a Y chromosomal effect on both aggression and thermoregulatory nest-building behavior in mouse lines either bidirecrionally selected for short (SAL) and long (LAL) attack latency or high (HIGH) and low (LOW) nest-building behavior. Using reciprocal crosses between SAL and LAL, and between HIGH and LOW, we found no indications for Y chromosomal effects on thermoregulatory nest-building behavior. As for aggression, we confirmed earlier studies on SAL and LAL, i.e., the origin of the Y chromosome influences attack latency, i.e., aggression. However, we did not find indications for a Y chromosomal effect on aggression in the HIGH and LOW lines. Since aggression and nest-building behavior have been shown to be characteristic parameters of two fundamentally different behavioral strategies, the present data underline the improbability of Y chromosomal genes underlying the genetic architecture of alternative behavioral strategies.     

Studies on plasminogen activator and other proteases in subcultured human vascular cells

Plasminogen activator activity (PAA) of human vascular cells in culture was quantitated in an assay system in which the conversion of purified plasminogen to plasmin was measured by activity against a soluble low-molecular-weight plasmin substrate. Reliable detection of PAA required cell lysis and use of membrane-disrupting detergents. After such treatment, PAA was found only in the 100,000 g subcellular fractions of human aortic smooth muscle and mixed populations of rabbit aortic cells. No corresponding activity was found in any fraction from human umbilical vein endothelial cells. In contrast, PAA was detected in significant amounts in intact mouse embryo fibroblasts (3T3 cells) used as controls. Very low levels of enzymatic activity against a spectrum of substrates preferentially amidolyzed by serine proteases were also demonstrable in human aortic smooth muscle or 3T3 fibroblast subcultures. Neither whole cell homogenates nor subcellular fractions demonstrated the previously described acid-labile inhibitor of PAA when assayed in this system. The above findings suggest that significant differences in PAA exist between various cell types and vascular segments. In addition, the subcellular localization and quantitatively low levels of PAA and other serine proteases found in human arterial and venous cells may reflect the presence of membrane-associated enzymes whose biological role is restricted to local homeostasis.     

Detection of human group C rotaviruses in Nigeria and sequence analysis of their genes encoding VP4, VP6, and VP7 proteins.

In a survey on the etiology of acute gastroenteritis in infants and young children in Nigeria, group C human rotaviruses were detected in two of 112 rotavirus positive stool specimens collected between 1999 and 2000. The VP7, VP6, and VP4 genes of the two Nigerian human group C rotavirus strains (Jajeri and Moduganari) were sequenced in this study. Comparative sequence analysis with other published human group C rotaviruses showed that the genes encoding the three structural proteins were remarkably conserved in primary structure with few mutations. The VP4 and VP7 genes from the two Nigerian strains were related more closely to each other than to those of other published strains, and formed a separate cluster on the phylogenetic tree. In contrast, it was of note that VP6 gene of strain Moduganari was related more closely to the Brazilian strain Belem than to the other Nigerian strain Jajeri. This is the first report of identification of human group C rotavirus in Nigeria and constitutes the first sequence data of human group C rotaviruses in the African continent.     

Human genetics of common mycobacterial infections

There is increasing interest in and understanding of the role of human genetic factors controlling susceptibility/resistance to infectious diseases. This is of particular importance for the two most common mycobacterial infections, tuberculosis and leprosy, because this will allow a genetic dissection of antimycobacterial immunity and should open new fields of preventive and therapeutic measures. In this review we will initially discuss various methods of genetic epidemiology that have been and are being developed to identify human genes controlling infectious diseases, and then illustrate the findings obtained in the numerous studies performed in tuberculosis and leprosy. Although the most convincing results were observed for HLA-DR2 and NRAMP1 (or a closely linked gene) in pulmonary tuberculosis and leprosy subtypes and for a 10p13 locus in paucibacillary leprosy, the molecular basis of their effects remains to be established.     

Adrenergic signaling plays a critical role in the maintenance of waking and in the regulation of REM sleep

Many experiments have suggested that the adrenergic system is important for arousal and the regulation of sleep/wake states. Electrophysiological studies have found strong correlations between the firing of adrenergic neurons and arousal state. Lesions of adrenergic neurons have been reported to cause changes in sleep/wake regulation, although findings have been variable and sometimes transient. To more specifically address the role of adrenergic signaling in sleep/wake regulation, we performed electroencephalographic and electromyographic recordings in mice with a targeted disruption of the gene for dopamine beta-hydroxylase, the enzyme that converts dopamine to norepinephrine. These mice are unable to synthesize the endogenous adrenergic ligands norepinephrine and epinephrine. The mutant mice sleep approximately 2 h more each day. The decrease in waking is due to a considerable decrease in the duration of waking bouts in spite of an increase in the number of waking bouts and transitions from sleep to waking. In contrast, the amount of rapid-eye-movement (REM) sleep is only half that in control mice due to a decrease in the number and duration of REM sleep bouts. Delta power is selectively increased in the mutant mice, and there is much less variation in non-REM sleep delta power over 24 h. After 6 h of total sleep deprivation during the first half of the light period, there is no rebound recovery of sleep time in the mutant mice. These results provide genetic evidence that adrenergic signaling acts to maintain waking and is important for the regulation of REM sleep and possibly sleep homeostasis.     

Amiloride analogues induce responses in isolated rat cardiovascular tissues by inhibition of Na+/Ca2+ exchange

Summary The role of inhibition of Na⁺/Ca²⁺ exchange in the positive inotropic, negative chronotropic and vasorelaxant responses to amiloride and some of its analogues was investigated in isolated cardiovascular tissues from female Wistar rats. The compounds tested were amiloride, 5-(N-ethyl-N-isopropyl)amiloride (EIPA, a potent inhibitor of Na⁺/H⁺ exchange), phenamil and 2,4-dimethylbenzamil (DMB), both potent Na⁺ channel inhibitors with activity against Na⁺/Ca²⁺ exchange, and 5-(N-4-chlorobenzyl)-2,4-dimethylbenzamil (CBDMB), a potent inhibitor of Na⁺/Ca²⁺ exchange with reduced activity against Na⁺ channels compared with its parent compound DMB.Phenamil, DMB and CBDMB increased the force of contraction of right ventricular papillary muscles with similar potencies (-log EC₅₀ values: 4.77 ± 0.06, 5.09 ± 0.09, 4.97 ± 0.17 respectively), while amiloride and EIPA gave small negative inotropic responses. All compounds gave negative chronotropic responses at similar concentrations to those which exerted inotropic effects. Inhibition of KCl contraction of endothelium-free aortic rings was observed with all compounds tested. Phenamil, DMB and CBDMB but not amiloride or EIPA showed a shift to the left of the concentration-response curves in the presence of intact endothelium.These results provide further evidence for positive inotropic and endothelium-dependent vasorelaxant effects of amiloride analogues mediated by inhibition of Na⁺/Ca²⁺ exchange. Send offprint requests to J. R. Bourke at the above address     

Amorphous‐Smectic Glassy Main‐Chain LCPs, 1. Poly(ether esters) Derived from Hydroxybibenzoic Acid and (R,S)‐ and (R)‐2‐Methylpropane‐1,3‐diol

The synthesis and the characterization of main‐chain liquid‐crystalline poly(ether esters), derived from hydroxybibenzoic acid and (R,S)‐ and (R)‐2‐methylpropane‐1,3‐diol, are reported. These polymers show an interesting thermal behavior. They develop mesophases with a slow rate of formation, allowing the easy quenching of the melt into: a) the glassy amorphous state, b) the glassy liquid‐crystalline state, or c) a mixture of both, depending on the thermal treatment. The extent of the transformation and the symmetry of the different phases have been determined by means of calorimetric and X‐ray diffraction methods. Dielectric spectroscopy results provide additional evidence for the detection of distinct glass transitions. The results show that the racemic polymer forms a low‐ordered SmC_alt mesophase, while a more ordered phase is obtained in the case of the enantiomerically pure polymer. The comparison of the properties of the different states evidences the special behavior and properties of the glass transition (T_g) in these polymers. Emphasis is paid to the location of the T_g of the liquid‐crystalline state in comparison to the T_g of the amorphous state. It is found that the glass transition of the SmC_alt glass in R,S‐PBO3 (the poly(ether ester) derived from hydroxybibenzoic acid and (R,S)‐2‐methylpropane‐1,3‐diol) appears at lower temperatures than the glass transition of the amorphous state. However, in R‐PBO3 (the poly(ether ester) derived from hydroxybibenzoic acid and (R)‐2‐methylpropane‐1,3‐diol), where the more ordered phase is present, the glass transition follows the classical tendency of semicrystalline polymers.

     

Syngeneic preference manifested by thymic stroma during development of thymocytes from bone marrow cells

The question whether major histocompatibility complex (MHC) recognition is expressed in interactions between thymocyte progenitors and thymic stroma cells was investigated in an organ culture system, in which inductive interactions between thymic stroma cells and thymocyte progenitors of different MHC haplotypes could be measured. Thymocyte-depleted fetal thymuses were reconstituted with mixtures of syngeneic and allogeneic bone marrow cells, which also differed in their Thy-1 allele. The relative repopulating ability of the cells was estimated by determining the percentage of emerging Thy-1.1+ vs. Thy-1.2+ thymocytes. Similar values of Thy-1+ cells of the bone marrow donor type developed when the thymus were reconstituted by bone marrow from donors which were either syngeneic or allogeneic to the thymic explants. However, when a 1:1 mixture of syngeneic and allogeneic cells was applied to the thymus, a syngeneic preference was manifested in development of Thy-1+ cells. When mixtures of bone marrow cells from C57BL/Ka (Thy-1.1) and B10.A MHC-congenic (Thy-1.2) mice were used, this developmental preference was found to map to the I-E region. Thymocytes derived from bone marrow cells allogeneic to the stroma, seeded on their own, manifested an advantage over allogeneic bone marrow cells from a different MHC haplotype, in a secondary reconstitution. This suggested that allogeneic bone marrow progenitor cells can be "educated" by the host thymic stroma to behave, in the competitive reconstitution, like syngeneic cells.