A critical review of the role of M2PYK in the Warburg effect

It is becoming generally accepted in recent literature that the Warburg effect in cancer depends on inhibition of M₂PYK, the pyruvate kinase isozyme most commonly expressed in tumors. We remain skeptical. There continues to be a general lack of solid experimental evidence for the underlying idea that a bottle neck in aerobic glycolysis at the level of M₂PYK results in an expanded pool of glycolytic intermediates (which are thought to serve as building blocks necessary for proliferation and growth of cancer cells). If a bottle neck at M₂PYK exists, then the remarkable increase in lactate production by cancer cells is a paradox, particularly since a high percentage of the carbons of lactate originate from glucose. The finding that pyruvate kinase activity is invariantly increased rather than decreased in cancer undermines the logic of the M₂PYK bottle neck, but is consistent with high lactate production. The “inactive” state of M₂PYK in cancer is often described as a dimer (with reduced substrate affinity) that has dissociated from an active tetramer of M₂PYK. Although M₂PYK clearly dissociates easier than other isozymes of pyruvate kinase, it is not clear that dissociation of the tetramer occurs in vivo when ligands are present that promote tetramer formation. Furthermore, it is also not clear whether the dissociated dimer retains any activity at all. A number of non-canonical functions for M₂PYK have been proposed, all of which can be challenged by the finding that not all cancer cell types are dependent on M₂PYK expression. Additional in-depth studies of the Warburg effect and specifically of the possible regulatory role of M₂PYK in the Warburg effect are needed.     

Action exerted by atropine sulfate on the luteinization phenomenon induced by a total gonadotropic preparation of prehypophysis at several stages of the estrus cycle in the rat

These experiments explored the effect of 70 mg atropine sulfate, and several doses of Gonadormone Byla, given at 1700 on diestrous I or at 1700 on diestrous II in the strains WI and WII rats derived in the authors' laboratory from Wistar rats. In Experiment 1 300 rats, 30 per group, received 2.5 or 5.0 mouse units of Gonadormone per 100 gm body weight at 1700 of diestrous I, with or without atropine, and were killed for serial ovarian sections at 1100 of proestrus. The 2.5 unit experime nt generated significant differences in frequency of luteinization between season of the year (p less than .001), between atropine and no atropine treatment (p less than .001), and season of atropine administration (p less than .05). Atropine decreased frequency of luteinization defined as proportion of a group having luteinized with or without retained ova. There were no differences in mean coefficients of ovulation, i.e., mean proportion of ovulated corpora lutea in each rat among all luteinized follicles, between rat strains or atropine treatments. The 5 unit dose of gonadotropin per 100 gm body weight increased luteinization 100% over the 2.5 unit dose. In the 2nd series of 180 rats, the frequency of luteinization induced by 1.25 units of gonadotropin was decreased by atropine (p less than .01), but the frequency of ovulation and response in the 2 rat strains did not differ. The results were interpreted as due in part to endogenous gonadotropin release, although atropine was thought to act directly on the ovary.     

Memory and chemical communication in the orientation of two mass-recruiting ant species

Summary The relative contribution of visual and chemical components in the orientation ofLasius niger andIridomyrmex humilis (Argentine ant) workers during mass recruitment to newly discovered food sources is analyzed over short time intervals. While both species orient in response to the trail pheromone, a large number ofL. niger foragers rapidly switch to a more individual orientation, based on their memory of environmental cues.I. humilis workers, on the other hand, predominantly use collective chemical cues. The effect of the number of reinforcements on visual learning and its interference with chemical communication show that olfactory cues always prevail in the Argentine ant. InL. niger, the proportion of ants orienting to visual cues is independent of the trail concentration. Detailed observations of the trail-laying behavior of individually marked foragers show that nearly all theI. humilis workers initially lay a trail, whereas only half theL. niger foragers do so. This proportion decreases considerably with the number of trips performed byL. niger workers, while remaining constant for the Argentine ants. These results are interpreted with respect to the species' behavioral ecology.     

Note on the formulation of a stochastic model of superinfection

We incorporate a process of removal (e.g., death) directly into the basic stochastic model for superinfection and recovery in order to describe explicitly the dynamics of infection within an individual. Formulae are derived for the mean duration of infection and the probability of removal during a bout of infection. A common method of approximating this joint process with a differential equation results in overestimation of these two quantities.     

Effect of atropine sulfate on the phenomena of follicular growth induced by a total anterior pituitary gonadotropic preparation during the estrus cycle in the rat

The question whether atropine inhibits follicular growth in rats induced by Gonadormone Byla was tested. 52 rats of strain WI, and 48 WII rats about 20 gm heavier, were injected at 1700 in diestrous I with 2.5 mouse units of gonadotropin per 100 gm body weight and 28 of each group also with 70 mg atropine sulfate sc, then serial ovarian sections were prepared at 1700 of proestrus. Atropine reduced the mean number of follicles 400 mcm in diameter or above (p less than .02), but did not affect their size distribution. A 2nd series of 48 rats were injected at 1700 of diestrous II with 1.5 units of gonadotropin per 100 gm body weight and half the rats with atropine. Again, atropine reduced the number of developing follicles (p less than .05) without affecting their mean diameter or size distribution.