Sleepy dialogues between cortex and hippocampus: who talks to whom?

During NREM sleep, neocortical neurons undergo near-synchronous transitions, every second or so, between UP states, during which they are depolarized and fire actively, and DOWN states, during which they are hyperpolarized and completely silent. In this issue of Neuron, Isomura et al. report that slow oscillations of membrane potential occur near-synchronously not only in neocortex but also in entorhinal cortex and subiculum. Within the hippocampus proper, pyramidal neurons lack the bistability of UP and DOWN states, but their firing is strongly modulated by cortical activity during the UP state. Intriguingly, many hippocampal neurons fire during the cortical DOWN state. Thus, during sleep UP states, the cortex can talk to the hippocampus, but it is unclear whether the hippocampus talks back.     

Kindlins, integrin activation and the regulation of talin recruitment to αIIbβ3

Talins and kindlins bind to the integrin β3 cytoplasmic tail and both are required for effective activation of integrin αIIbβ3 and resulting high-affinity ligand binding in platelets. However, binding of the talin head domain alone to β3 is sufficient to activate purified integrin αIIbβ3 in vitro. Since talin is localized to the cytoplasm of unstimulated platelets, its re-localization to the plasma membrane and to the integrin is required for activation. Here we explored the mechanism whereby kindlins function as integrin co-activators. To test whether kindlins regulate talin recruitment to plasma membranes and to αIIbβ3, full-length talin and kindlin recruitment to β3 was studied using a reconstructed CHO cell model system that recapitulates agonist-induced αIIbβ3 activation. Over-expression of kindlin-2, the endogenous kindlin isoform in CHO cells, promoted PAR1-mediated and talin-dependent ligand binding. In contrast, shRNA knockdown of kindlin-2 inhibited ligand binding. However, depletion of kindlin-2 by shRNA did not affect talin recruitment to the plasma membrane, as assessed by sub-cellular fractionation, and neither over-expression of kindlins nor depletion of kindlin-2 affected talin interaction with αIIbβ3 in living cells, as monitored by bimolecular fluorescence complementation. Furthermore, talin failed to promote kindlin-2 association with αIIbβ3 in CHO cells. In addition, purified talin and kindlin-3, the kindlin isoform expressed in platelets, failed to promote each other's binding to the β3 cytoplasmic tail in vitro. Thus, kindlins do not promote initial talin recruitment to αIIbβ3, suggesting that they co-activate integrin through a mechanism independent of recruitment.     

Ribosome biogenesis and p53: Who is regulating whom?

Comment on: Krastev DB, et al. Nat Cell Biol 2011; 13:809-18.     

Olfactory axon pathfinding: who is the pied piper?

Mammalian olfactory sensory neurons that express a particular odorant receptor (OR) project axons to the same few glomeruli in the olfactory bulb. In this issue of Neuron, Vassalli et al. use OR minigenes that coexpress histochemical markers and show that the determinants in the sensory neurons required to generate the stereotyped olfactory bulb map are the same as those needed for appropriate expression of the OR.     

Hormone treatments and preventive strategies in the aging male: whom and when to treat?

Sex hormones have a broad range of actions in regulating very diverse systems throughout life. Testosterone and other related hormones change with age to varying degrees and may induce pathophysiological changes and the clinical condition known as andropause. Androgen replacement is the accepted but not the only possible treatment for andropause. The presence of clinical symptoms, including a loss of sexual function, intellectual capacity, lean body mass, or bone mineral density; alterations in body hair, skin, or sleep pattern; or increases in visceral fat, together with low levels of serum testosterone characterize andropause. An appreciation of the potentially undesirable impact of androgens on the biology of prostate cancer, as well as possibly the cardiovascular system, is necessary. However, proper evaluation of aging men with symptoms of andropause will result in a decision to initiate androgen therapy in some aging men.     

Metabolic and hedonic drives in the neural control of appetite: who is the boss?

Obesity is on the rise in all developed countries, and a large part of this epidemic has been attributed to excess caloric intake, induced by ever present food cues and the easy availability of energy dense foods in an environment of plenty. Clearly, there are strong homeostatic regulatory mechanisms keeping body weight of many individuals exposed to this environment remarkably stable over their adult life. Other individuals, however, seem to eat not only because of metabolic need, but also because of excessive hedonic drive to make them feel better and relieve stress. In the extreme, some individuals exhibit addiction-like behavior toward food, and parallels have been drawn to drug and alcohol addiction. However, there is an important distinction in that, unlike drugs and alcohol, food is a daily necessity. Considerable advances have been made recently in the identification of neural circuits that represent the interface between the metabolic and hedonic drives of eating. We will cover these new findings by focusing first on the capacity of metabolic signals to modulate processing of cognitive and reward functions in cortico-limbic systems (bottom-up) and then on pathways by which the cognitive and emotional brain may override homeostatic regulation (top-down).     

A size dependent predator-prey interaction: who pursues whom?

We investigate the properties of an (age, size) -structured model for a population of Daphnia that feeds on a dynamical algal food source. The stability of the internal equilibrium is studied in detail and combined with numerical studies on the dynamics of the model to obtain insight in the relation between individual behaviour and population dynamical phenomena. Particularly the change in the (age, size)-relation with a change in the food availability seems to be an important behavioural mechanism that strongly influences the dynamics. This influence is partly stabilizing and partly destabilizing and leads to the coexistence of a stable equilibrium and a stable limit cycle or even coexistence of two stable limit cycles for the same parameter values. The oscillations in this case are characterized by drastic changes in the size-structure of the population during a cycle. In addition the model exhibits the usual predator-prey oscillations that characterize Lotka-Volterra models.     

Biomedical research practice and therapeutic practice: to whom does the human body belong?

Who owns the human body? This issue has been formerly raised about the status of the slave. Today, it has become a prominent stake for when reflecting on biomedical research and healthcare practices. In our cultures, many answers may be given to this question : they are derived from philosophical or theological traditions ; they are borrowed from anthropological, sociological or psychological knowledge ; they may be formulated in a moral or political perspective. All of them give different insights and reveal one of the various dimensions of the question. When examining the status of the body and its relation to the human subject in the various stages of his/her life (including his/her death), one of the main difficulties is to deal with each of these answers and to understand how they meet and interact in the public debate. Another matter is related to the fact that law also plays a crucial role in the process of giving an answer to this question. In our book, A qui appartient le corps humain ? Médecine, politique et droit (Paris, Belles Lettres, 2004), Claire Crignon-De Oliveira and I have tried to deal with both difficulties. In this article, I focus on the meaning of the various law traditions. In western world, the laws are all derived, up to a certain extent, from the Roman tradition. Whether they have chosen to consider the human body as a property or to associate the body to the person, they have taken very different options. However, an examination of the ways laws are elaborated on this topic shows that these two conceptions can meet in unexpected manners and that lawmaking can give creative answers to both the problem of protecting the person and to the requirements of biomedical research and healthcare practices.     

Virulence factors of Trypanosoma cruzi: who is who?

The aim of this review is to gather the current knowledge of Trypanosoma cruzi's virulence factors described to date in an integrative way, relating these with the parasite's life cycle and trying to elucidate their importance in each process. Several aspects relevant for the parasite's survival, such as invasion, resistance to oxidative damage, escape from the phagolysosomal vacuole and differentiation, among others, will be discussed. However, there is still a lot to learn about what virulence really means in T. cruzi and which parasite molecules are absolutely required to make T. cruzi one of the most successful pathogens to invade, survive and persist in a mammalian host.