Why do we eat?

The urge to eat is the main apparent issue underlying obesity. Although vast information regarding the physiology and psychology of eating behavior has been accumulated, a comprehensive concept is still missing. The model presented suggests that feeding behavior is ultimately controlled by the rate of work performed in the muscle or in an as yet unidentified compartment. It suggests a novel approach of a dynamic set-point weight and explains why diets usually fail to resolve the disorder while physical activity is beneficial in losing excess weight. Obesity is presented as a syndrome of high efficiency of energy conversion resulting in a variety of symptoms of which over-weight is only the more apparent. Other symptoms manifested in the predisposition to a variety of illnesses constitute the main health problem and can prevail in the obese subject even without the excess weight. Therefore, resolution of the disorder requires developing approaches which directly affect the efficiency of energy conversion.

Precontact mammalian sperm-egg communication and role in fertilization.

In creatures with external fertilization, e.g., metazoa, it is well established that there is precontact sperm-egg communication in the form of chemotaxis. An intriguing question is whether also in mammals, where fertilization is internal and the need for precontact sperm-egg communication is not self-evident, such a process occurs and what its physiological significance may be. Here we review the evidence related to such a process in mammals, evidence which suggests that sperm attraction to the ovulated egg may indeed occur. On the basis of the available data we propose a hypothesis, according to which a sperm population is heterogeneous with respect to its physiological state; some spermatozoa are at a physiological state ready for fertilizing an egg, while others are premature or overmature. According to the hypothesis this is a dynamic state; the population of fertilizing spermatozoa gradually loses its potency and, at the same time, other spermatozoa mature and acquire fertilizing ability. After ovulation, only the fertilizing spermatozoa are attracted to the egg, while the rest are either repelled or inhibited and thus prevented from reaching the egg. The potential significance of sperm-egg communication is discussed.

Bacterial catalysis of nitrosation: involvement of the nar operon of Escherichia coli.

We have developed a rapid and sensitive fluorimetric method, based on the formation of a fluorescent product from nitrosation of 2,3-diaminonaphthalene, for measuring the ability of bacteria to catalyze nitrosation of amines. We have shown in Escherichia coli that nitrosation can be induced under anaerobic conditions by nitrite and nitrate, that formate is the most efficient electron donor for this reaction, and that nitrosation may be catalyzed by nitrate reductase (EC 1.7.99.4). The narG mutants defective in nitrate reductase do not catalyze nitrosation, and the fnr gene is essential for nitrosation. Induction by nitrite or nitrate of nitrosation, N2O production, and nitrate reductase activity all require the narL gene.

Heterotrophic nitrification by intestinal microorganisms.

From studies of nitrate balance in man and analyses of fecal and ileostomy samples, the possibility that nitrite and nitrate are formed de novo in the intestine, possibly by heterotrophic nitrification has emerged. This proposition significantly alters our previous conceptions of man's exposure to nitrite and suggests that nitrite may play a role in the cause of intestinal cancer. Heterotrophic nitrification has been demonstrated in various microorganisms. Our work has shown that intestinal heterotrophic microbial isolates from man are able to oxidize nitrogenous compounds to nitrite. These isolates include both procaryotes and eucaryotes.

Sequential acquisition of chemotactic responsiveness by human spermatozoa.

Recent studies have indicated that human spermatozoa respond to follicular fluid by attraction to chemotactic factor(s) in the fluid, accompanied by enhancement of motility and ultimately hyperactivation. In this study, we quantified the sperm response. We exposed spermatozoa to a gradient of a chemotactically active fraction of follicular fluid (denoted as "the attractant") and separated the spermatozoa that accumulated in the attractant and those that did not. We thus obtained two subpopulations: one enriched with chemotactically responsive spermatozoa, and one deficient in such spermatozoa. The fraction of the responsive spermatozoa out of the total sperm population was 2-12% at any measured time point. With time, the responsive spermatozoa lost their ability to be attracted, while such activity was gradually acquired by the subpopulation originally deficient in responsive spermatozoa. These results indicate that the identity of responsive spermatozoa is continuously changing. If the in vitro results are representative of the physiological conditions in vivo, they imply that the role of sperm chemotaxis combined with enhanced motility may be to select capacitated spermatozoa and bring them to the egg. Such a mechanism may, over an extended period of time, increase the prospect that an egg will meet capacitated spermatozoa as soon as it ovulates.

Sperm attraction to a follicular factor(s) correlates with human egg fertilizability.

Spermatozoa normally encounter the egg at the fertilization site (in the Fallopian tube) within 24 hr after ovulation. A considerable fraction of the spermatozoa ejaculated into the female reproductive tract of mammals remains motionless in storage sites until ovulation, when the spermatozoa resume maximal motility and reach the fertilization site within minutes. The nature of the signal for sperm movement is not known, but one possible mechanism is attraction of spermatozoa to a factor(s) released from the egg. We have obtained evidence in favor of such a possibility by showing that human spermatozoa accumulate in follicular fluid in vitro. This accumulation into follicular fluid was higher by 30-260% than that observed with buffer alone and was highly significant (P less than 10(-8)). Not all of the follicular fluids caused sperm accumulation; however, there was a remarkably strong correlation (P less than 0.0001) between the ability of follicular fluid from a particular follicle to cause sperm accumulation and the ability of the egg, obtained from the same follicle, to be fertilized. These findings suggest that attraction may be a key event in the fertilization process and may give an insight into the mechanism underlying early egg-sperm communication.

Atrial natriuretic peptide attracts human spermatozoa in vitro.

Here we report that atrial natriuretic peptide (ANP), a known activator of particulate guanylate cyclase, induces attraction and swimming speed enhancement of human spermatozoa in vitro. Using capillary assays under a variety of experimental conditions (ascending or descending gradients of ANP, or no gradient at all) and microscopic assays in which individual spermatozoa could be followed, we found that spermatozoa followed the gradient of ANP and accumulated in it. Speed enhancement was detected in the presence of ANP without a gradient. These observations suggest either that an ANP-like substance is the physiological attractant for human spermatozoa, or, more likely, that ANP directly affects guanylate cyclase in a manner similar to that caused by the physiological attractant.

Chemotaxis and chemokinesis of human spermatozoa to follicular factors.

Human spermatozoa accumulate in vitro in diluted follicular fluids obtained from follicles from which the eggs have been fertilized. Using capillary assays under a variety of experimental conditions (ascending or descending gradients of follicular fluid, or no gradient at all) and microscopic assays in which individual spermatozoa could be followed, we found that the sperm accumulation in follicular fluid was the result of both sperm chemotaxis and chemokinesis and eventually hyperactivation-like motility. We determined the optimal conditions for sperm accumulation, which involved sperm preincubation (possibly to induce sperm capacitation) and proper dilution of follicular fluid. In all the assays, the net accumulation was low, probably reflecting the chemotactic responsiveness of only a small fraction of the sperm population at any given time. We partially fractionated follicular fluid in a Centricon microconcentrator (Amicon, Danvers, MA) and by acetone precipitation, and found that at least one of the chemotactic factors is a small (< 10-kDa) molecule that is probably nonhydrophobic. This is the first time that sperm chemotaxis and chemokinesis in response to a follicular factor(s) in mammals has been established and has been distinguished from other processes that might cause sperm accumulation. The physiological significance of these findings is discussed.