Neonatal asphyxia and hyperthermia and cognitive deficits in adult rats: Role of iron

We compared effects of a critical neonatal anoxia, applied in Wistar rats at body temperatures of 33, 37 and 39 °C, on memory performance in adulthood. Because hyperthermic–anoxic neonates suffer from hyperferremia an additional group of rats, exposed to anoxia at 39 °C, was injected with deferoxamine, a chelator of iron. At the age of 4 and 12 months all rats were examined in hole board, typical maze and Morris maze.     

Uninterrupted growth in a non-polar hadrosaur explains the gigantism among duck-billed dinosaurs

Duck-billed dinosaurs (Hadrosauridae) were the most common ornithopods of the Late Cretaceous. Second only to sauropods and in many cases exceeding the sizes of the largest land mammals (such as indricotheres or proboscideans), they are among the largest terrestrial herbivores to have walked the Earth. Despite their gigantic size, diversity and abundance, their growth strategies remain poorly understood. Here, we examine the bone microstructure of several Mongolian hadrosauroids of varied adult sizes. The small and middle-sized species have lines of arrested growth (LAGs). On the other hand, one of the largest duck-billed dinosaurs, Saurolophus angustirostris, shows uninterrupted growth, comparable with other big hadrosaurs for which the lack of cyclical growth arrests was interpreted as a result of living in the polar region. Since both of the studied taxa inhabited warmer, continental, monsoon-influenced environments of the Late Cretaceous Mongolia, we propose that the absence of LAGs is not a climatic-driven condition but rather connected with the animal's size (i.e. ontogeny). Our results show that, like sauropods, hadrosaurs changed their growth dynamics from cyclical to continuous during their evolution, which made it possible for them to achieve comparable body sizes.     

Conditional drug screening shows that mitotic inhibitors induce AKT/PKB-insensitive apoptosis

The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is frequently upregulated in human cancer. Activation of this pathway has been reported to be associated with resistance to various chemotherapeutical agents. We here used a chemical biology/chemical informatic approach to identify apoptotic mechanisms that are insensitive to activation of the PI3K/AKT pathway. The National Cancer Institute (NCI) Mechanistic Set drug library was screened for agents that induce apoptosis in colon carcinoma cells expressing a constitutively active form of AKT1. The cytotoxicity screening data available as self-organized maps at the Developmental Therapeutics Program (DTP) of the NCI was then used to classify the identified compounds according to mechanism of action. The results showed that drugs that interfere with the mitotic process induce apoptosis which is comparatively insensitive to constitutive AKT1 activity. The conditional screening approach described here is expected to be useful for identifying relationships between the state of activation of signaling pathways and sensitivity to anticancer agents.     

Cellular senescence in skin-related research: Targeted signaling pathways and naturally occurring therapeutic agents

Despite the growing interest by researchers into cellular senescence, a hallmark of cellular aging, its role in human skin remains equivocal. The skin is the largest and most accessible human organ, reacting to the external and internal environment. Hence, it is an organ of choice to investigate cellular senescence and to target root-cause aging processes using senolytic and senomorphic agents, including naturally occurring plant-based derivatives. This review presents different aspects of skin cellular senescence, from physiology to pathology and signaling pathways. Cellular senescence can have both beneficial and detrimental effects on the skin, indicating that both prosenescent and antisenescent therapies may be desirable, based on the context. Knowledge of molecular mechanisms involved in skin cellular senescence may provide meaningful insights for developing effective therapeutics for senescence-related skin disorders, such as wound healing and cosmetic skin aging changes.