Nonsemper systems optimization

The optimization of discrete systems constrained in an unusual way is discussed. Moreover, it is supposed that for such systems, here called "nonsemper," the selection of the control policy consists in the choice of the value of the control variables as well as in the allocation over time of the control action itself. A simple functional equation suitable for carrying on the solution of the problem is derived via dynamic programming.     

The nucleus negatively controls the synthesis of mitochondrial proteins in the sea urchin egg

Enucleation of Paracentrotus lividus eggs, followed by parthenogenetic activation induces a sharp increase in the synthesis of mitochondrial proteins as shown by electrofluorography after in vivo labeling with radioactive amino acids. These results further substantiate the hypothesis that the cell nucleus negatively controls mitochondrial replication in the sea urchin egg.     

Interleukin-1 mediates a rapid inflammatory response after injection of adenoviral vectors into the brain

Adenovirus-mediated gene transfer into the brain is associated with significant inflammation and activation of anti-vector and anti-transgene immune responses that curtail the gene delivery of adenoviruses and therapeutic efficacy. Elucidating the molecular mediators of inflammatory and immune responses to adenoviruses injected into the brain should allow us to inhibit their inflammatory actions, thereby reducing vector clearance and enhance adenoviral-mediated gene transfer into the CNS. Cytokines are primary mediators of the immune response and are released during inflammation. Here we report for the first time that injection of replication-deficient adenovirus vectors into the cerebral ventricles of rats causes a rapid increase in body temperature. This fever response precedes any vector-encoded transgene expression and occurs with vectors encoding no transgene, as well as with vectors encoding a therapeutic transgene i.e., HSV1-thymidine kinase. No fever is detected after infection of the striatum, an important brain target in studies on neurodegeneration. After infection of the brain ventricles, CSF levels of immunoreactive tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta increase significantly (up to 300-fold). In the hypothalamus, the locus of thermoregulation in the brain, only IL-1beta and IL-6 are significantly elevated. A neutralizing TNF-alpha antibody has no effect on adenovirus-induced fever. However, pretreatment with either the IL-1 receptor antagonist or the cyclooxygenase inhibitor flurbiprofen completely abolishes adenovirus-induced fever, suggesting that IL-1 and prostaglandins are direct mediators of this response. These results are the first to demonstrate that IL-1, but not TNF-alpha, is the main mediator of a very early inflammatory response to adenovirus in the brain.     

South Turkwel: a new pliocene hominid site in Kenya

New fossils discovered south of the Turkwel River in northern Kenya include an associated metacarpal, capitate, hamate, lunate, pedal phalanx, mandibular fragment, and teeth. These fossils probably date to around 3.5 m.y.a. Faunal information suggests that the environment at South Turkwel was predominantly bushland. The mandibular and dental remains are fragmentary, but the postcranial fossils are informative. Comparisons with Australopithecus, modern human, chimpanzee and gorilla hand bones suggest that the Turkwel hominid was most like Australopithecus afarensis and A. africanus. Carpometacarpal articulations are intermediate between those of modern humans and African apes, suggesting enhanced gripping capabilities compared with extant apes. The hamulus was strikingly large, similar in proportion only to Neandertals and some gorillas, suggesting the presence of powerful forearms and hands. There are no indicators of adaptations to knuckle-walking or suspensory locomotion in the hand, and the pedal phalanx suggests that this hominid was habitually bipedal.