Looking forward, looking back

Amgen's retrospective sortie into personalized Vectibix treatment poses some difficult questions for regulators concerning the oversight of companion diagnostics.     

Diet and asthma: looking back,moving forward

Asthma is an increasing global health burden, especially in the western world. Public health interventions are sought to lessen its prevalence or severity, and diet and nutrition have been identified as potential factors. With rapid changes in diet being one of the hallmarks of westernization, nutrition may play a key role in affecting the complex genetics and developmental pathophysiology of asthma. The present review investigates hypotheses about hygiene, antioxidants, lipids and other nutrients, food types and dietary patterns, breastfeeding, probiotics and intestinal microbiota, vitamin D, maternal diet, and genetics. Early hypotheses analyzed population level trends and focused on major dietary factors such as antioxidants and lipids. More recently, larger dietary patterns beyond individual nutrients have been investigated such as obesity, fast foods, and the Mediterranean diet. Despite some promising hypotheses and findings, there has been no conclusive evidence about the role of specific nutrients, food types, or dietary patterns past early childhood on asthma prevalence. However, diet has been linked to the development of the fetus and child. Breastfeeding provides immunological protection when the infant''s immune system is immature and a modest protective effect against wheeze in early childhood. Moreover, maternal diet may be a significant factor in the development of the fetal airway and immune system. As asthma is a complex disease of gene-environment interactions, maternal diet may play an epigenetic role in sensitizing fetal airways to respond abnormally to environmental insults. Recent hypotheses show promise in a biological approach in which the effects of dietary factors on individual physiology and immunology are analyzed before expansion into larger population studies. Thus, collaboration is required by various groups in studying this enigma from epidemiologists to geneticists to immunologists. It is now apparent that this multidisciplinary approach is required to move forward and understand the complexity of the interaction of dietary factors and asthma.     

Submergence research using Rumex palustris as a model; looking back and going forward

Flooding is a phenomenon that destroys many crops worldwide. During evolution several plant species evolved specialized mechanisms to survive short- or long-term waterlogging and even complete submergence. One of the plant species that evolved such a mechanism is Rumex palustris. When flooded, this plant species is capable to elongate its petioles to reach the surface of the water. Thereby it restores normal gas exchange which leads to a better survival rate. Enhanced levels of ethylene, due to physical entrapment, is the key signal for the plant that its environment has changed from air to water. Subsequently, a signal transduction cascade involving at least four (classical) plant hormones, ethylene, auxin, abscisic acid, and gibberellic acid, is activated. This results in hyponastic growth of the leaves accompanied by a strongly enhanced elongation rate of the petioles enabling them to reach the surface. Other factors, among them cell wall loosening enzymes have been shown to play a role as well.     

Looking backwards, looking forward: hopes for bioethics' next twenty-five years

I reflect on the past, present, and future of the field of bioethics. In so doing, I offer a very situated overview of where bioethics has been, where it now is, where it seems to be going, where I think we could do better, and where I dearly hope the field will be heading. I also propose three ways of re-orienting our theoretic tools to guide us in a new direction: (1) adopt an ethics of responsibility; (2) explore the responsibilities of various kinds of actors and relationships among them; (3) expand the types of participants engaged in bioethics.     

l-glutamate as a central neurotransmitter: looking back

The high concentration in brain of unbound l-glutamic acid (in its anionic form, l-glutamate) fuelled considerable speculation as to its role in central nervous function more than 50 years ago. Claims in the 1940s that it could improve cognitive acuity in patients with mental impairment were particularly intriguing, though later refuted. In the early 1950s Hayashi [(1954) Keio J. Med. 3, 183-192] found that l-glutamate could cause convulsions and proposed that it might be a central synaptic transmitter. Soon thereafter, Curtis and colleagues [Curtis, Phillis and Watkins (1959) Nature (London) 183, 611] showed that l-glutamate depolarized and excited central neurons, as expected for an excitatory transmitter; however, various aspects of the action of l-glutamate seemed to argue strongly against a transmitter function. This negative view prevailed for some 20 years, before compelling evidence for such a role was adduced. Over the last two decades, extensive research has revealed a host of glutamate receptor subtypes, subserving several different functions in excitatory synaptic transmission. This paper gives a very brief and personal overview of the development of the field over the last 50 years from a mainly pharmacological standpoint.