In search of tuberculosis virulence genes

The identity of the virulence genes that enable tuberculosis organisms to survive in macrophages and to induce the features of tuberculosis remains largely unknown. Numerous putative virulence genes have been identified, but so far there is only conclusive evidence for the role of two genes, KatG and rpoV, in virulence.     

Is there only one type of male handicap?

The handicap principle has been one of the most important developments in sexual selection theory. Numerous theoretical papers have considered whether extreme male ornaments could have arisen through female choice by being handicaps to the male. These models have been defined as belonging to one of three categories: (i) Zahavi's (J. theor. Biol. 53, 205 (1975)); (ii) the revealing; or (iii) the condition-dependent handicap. Here I discuss whether the division is still helpful for empirical purposes, or whether handicaps are not best considered as being condition dependent. I argue that in fact the revealing and condition-dependent handicaps are indistinguishable empirically, and that the 'Zahavi' handicap models arose due to a misunderstanding of what Zahavi originally proposed, which was in fact a condition-dependent handicap.     

Developmental and behavioral effects of prenatal primidone exposure in the rat

Pregnant Sprague-Dawley rats were administered primidone (PRM) by oral gavage on gestation days 8-17 in doses of 0.40, and 80 mg/kg. Although these doses of PRM did not produce significant differences in litter size, birth weight, mortality, date of attainment of developmental landmarks or measures of preweaning reflex and motor development, there were a number of significant differences that developed as the animals approached and entered adulthood. When tested as adults, the 80 mg/kg male rats showed a deficit in the performance of an eight-arm radial maze task. These same animals showed a significant reduction in open field activity when tested as adults. In addition, both male and female PRM-treated animals showed reduced body weights at different periods corresponding to onset of sexual maturation during development. These findings are consistent with the larger body of literature reporting on the neurobehavioral teratology of phenobarbital, including its ability to produce lesions in the hippocampus and endocrine dysfunction resulting in reproductive deficits. These results suggest that PRM produces its adverse effects as a result of its metabolism to phenobarbital, which in turn affects the limbic system.     

Protein kinase A activators inhibit agonist induced prostaglandin production in human amnion

Prostaglandin (PG) production by human amnion has been postulated to have a role in the onset of labor. Previous work by ourselves and others has demonstrated that oxytocin, phorbol esters and epidermal growth factor (EGF) increase PGE2 production in human amnion cells by activation of the Phospholipase C/Protein Kinase C (PKC) cascade system. The present study was undertaken to determine the effect of prior activation of the Adenylate Cyclase cascade system upon subsequent stimulation of PGE2 production by oxytocin, phorbol 12-myristate-13-acetate (PMA) or EGF in amnion cells and membrane discs. Isoproterenol, forskolin and dibutyryl cyclic adenosine monophosphate (dbcAMP) were utilized to activate the Adenylate Cyclase system at the receptor, enzyme and second messenger level. In control amnion cells, oxytocin, PMA and EGF each provoked dose dependent increases in PGE2 production. In cells preincubated with dbcAMP, forskolin or isoproterenol, agonist stimulated PGE2 production was markedly (50-90%) inhibited (p < 0.01). Inhibition was dose dependent upon preincubator concentrations. Maximal inhibition by adenylate cyclase activators occurred with 2-4 h of preincubation. In membrane discs, forskolin preincubation also inhibited oxytocin, PMA and EGF stimulation of PGE2 production. Activation of the Adenylate Cyclase system in human amnion cells or membrane discs inhibits the subsequent action of potent stimulators of PGE2 production in human amnion.     

ACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes

Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesterol esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. Minor changes in subsequent structure were found to have a significant effect in optimization of the biological activity of this series of compounds.     

Muscle-ligament interactions at the knee during walking.

A two-dimensional mathematical model of the knee is used with gait analysis to calculate muscle, cruciate ligament and tibio-femoral contact forces developed at the knee during normal level walking. Ten normal adult subjects--four females and six males--participated. The knee model is based upon a four-bar linkage comprising the femur, tibia and two cruciate ligaments. It takes account of the rolling and sliding of the femur on the tibia during flexion/extension and the changes in direction of the ligaments and muscle tendons. We considered forces transmitted by six elements: quadriceps, hamstrings, gastrocnemius, anterior and posterior cruciate ligaments, and tibio-femoral contact. The equations of mechanics can be used to determine the absolute values of only three of the knee forces simultaneously, so that twenty limiting solutions of three of the six forces were considered. A limiting solution was rejected if any of the three forces were negative, corresponding to compressive muscle or ligament forces, or tensile contact forces. These constraints always reduced and at times removed the redundancy of the knee structures. The high incidence of predicted single muscle activity, supported by electromyography, suggested that the ligaments play a significant role in load transmission during gait. The temporal patterns of muscle and ligament activity and ligament force magnitudes were sensitive to the choice of model parameters. The analysis showed that each of four possible minimum principles of muscle selection--minimal muscle force, muscle stress, ligament force and contact force--was unlikely to be valid throughout the walking cycle.     

Motion Planning for Redundant Manipulators Using a Floating Point Genetic Algorithm

This paper deals with the trajectory planning problem for redundant manipulators. A genetic algorithm (GA) using a floating point representation is proposed to search for the optimal end-effector trajectory for a redundant manipulator. An evaluation function is defined based on multiple criteria, including the total displacement of the end-effector, the total angular displacement of all the joints, as well as the uniformity of Cartesian and joint space velocities. These criteria result in minimized, smooth end-effector motions. Simulations are carried out for path planning in free space and in a workspace with obstacles. Results demonstrate the effectiveness and capability of the proposed method in generating optimized collision-free trajectories.     

Transient Response and Fixed Pattern Noise in Logarithmic CMOS Image Sensors

Logarithmic CMOS image sensors are appealing for their high-contrast and high-speed response but they require postprocessing to achieve high-quality images. Previously published work has explained the fixed pattern noise (FPN) in these image sensors using a steady-state analysis. This paper explains how the transient response of the readout circuit may also contribute to FPN. Thus, the performance of these CMOS cameras may be optimized with a proper understanding of the transient response, which is explained here through modeling and simulation with some experimental validation. In particular, the gain variation of a logarithmic camera is shown to be caused primarily by premature digitization. As logarithmic and linear active pixel sensors use similar circuits, some results in this paper, e.g., an analysis of readout capacitance, apply equally to the latter.