A model for the sequential dominance of antigenic variants in African trypanosome infections.

Trypanosoma brucei infects various domestic and wild mammals in equatorial Africa. The parasite's genome contains several hundred alternative and highly diverged surface antigens, of which only a single one is expressed in any cell. Individual cells occasionally change expression of their surface antigen, allowing them to escape immune surveillance. These switches appear to occur in a partly random way, creating a diverse set of antigenic variants. In spite of this diversity, the parasitaemia develops as a series of outbreaks, each outbreak dominated by relatively few antigenic types. Host-specific immunity eventually clears the dominant antigenic types and a new outbreak follows from antigenic types that have apparently been present all along at low frequency. This pattern of sequential dominance by different antigenic types remains unexplained. I use a mathematical model of parasitaemia and host immunity to show that small variations in the rate at which each type switches to other types can explain the observations. My model shows that randomly chosen switch rates do not provide sufficiently ordered parasitaemias to match the observations. Instead, minor modifications of switch rates by natural selection are required to develop a sequence of ordered parasitaemias.     

A neural network model of speech acquisition and motor equivalent speech production

This article describes a neural network model that addresses the acquisition of speaking skills by infants and subsequent motor equivalent production of speech sounds. The model learns two mappings during a babbling phase. A phonetic-to-orosensory mapping specifies a vocal tract target for each speech sound; these targets take the form of convex regions in orosensory coordinates defining the shape of the vocal tract. The babbling process wherein these convex region targets are formed explains how an infant can learn phoneme-specific and language-specific limits on acceptable variability of articulator movements. The model also learns an orosensory-to-articulatory mapping wherein cells coding desired movement directions in orosensory space learn articulator movements that achieve these orosensory movement directions. The resulting mapping provides a natural explanation for the formation of coordinative structures. This mapping also makes efficient use of redundancy in the articulator system, thereby providing the model with motor equivalent capabilities. Simulations verify the model's ability to compensate for constraints or perturbations applied to the articulators automatically and without new learning and to explain contextual variability seen in human speech production.Supported in part by AFOSR F49620-92-J-0499     

Determination of adenosine triphosphate in human semen to estimate the fertilizing potential and to quantify sperm antibodies

The measurement of the ATP content of fresh semen is as accurate as the estimation of sperm motility by conventional methods in discriminating between semen of fertile versus subfertile men. The ATP content of frozen thawed donor semen is correlated with the probability of conception per cycle of insemination. Exact quantification of cytotoxic sperm antibodies in serum is possible with the adenosine-triphosphate-release-cytotoxicity test, since measurement is free of the bias of microscopic examination. The procedure has been simplified by testing only one serum dilution and calculating the ‘sperm toxicity index’.     

Long-term effects of dietary isoflavones on uterine gene expression profiles

Isoflavones (ISOs) are bioactive food ingredients of the traditional East Asian diet and currently discussed as alternatives to classical hormone replacement therapies and for reducing the prevalence of hormone-dependent cancers. Although there are many studies on ISOs, not much is known about their long-term effects.Therefore, we performed an animal experiment analyzing the effects of three different diets: a phytoestrogen-free diet, a diet supplemented with genistein (700 μg/g diet) and an ISO-high diet (232 μg daidzein and 240 μg genistein/g) at two distinct time points, juvenile (21 days) and adult (97 days). Exposure started prior to mating of the parents and throughout the life of the offspring.We observed a stronger increase of uterine wet weights in juvenile offspring with genistein exposure (1018 ± 350 mg/kg BW) than with ISO-high diet (497 ± 133 mg/kg BW). Whereas the expression of proliferation related genes (PCNA; Ki67; IGF-1; IGF-1R), analyzed by real-time-qPCR and Western blot, were significantly down-regulated in juvenile animals exposed to genistein. Additionally, genistein exposure led to estrogenic responses, observed upon increase of complement C3 and decrease of estrogen receptors gene expressions, while the exposure to ISO-high diet did not show these effects.In conclusion, both the time point on which phytoestrogen exposure starts together with the composition of the ingested phytoestrogen containing diet are of great importance for the biological response of the offspring.     

Functional morphology of the neck organ in Artemia salina nauplii

Fine structure of the ion transporting epithelium of the neck organ in the brine shrimp (Artemia salina) nauplius is described. The neck organ is a dome-like gland situated atop the cephalothorax of the larva and is composed of 50 to 60 cuboidal epithelial cells. These cells possess many of the characteristics of salt-secretory cells from other tissues. They contain many mitochondria and exhibit a high degree of plasma membrane elaboration. This membrane amplification takes two forms; the apical plasmalemma is infolded into irregular loops, while the basal and lateral membranes penetrate the cytoplasm in the form of branching sinusoids. The labyrinth of tubular reticulum thus formed fills most of the cell volume. Mitochondria in the labyrinth are often in intimate contact with these tubular membranes and regular arrays of parallel mitochondria with constricted intervening sinusoids are often observed. Other organelles including Golgi complexes, multivesicular bodies, and rough endoplasmic reticulum are also numerous, particularly in the narrow rim of cytoplasm which lies between the apical infolds and the labyrinth. Yolk platelets and glycogen fields are conspicuous in the basal perinuclear regions of the cells.