Weekly Articles

The 2009 H1N1 Virus in its Historical Context

Of the 16 known serotypes of influenza A haemagglutinin, 6 have been isolated from humans at the molecular level (H1, H2, H3, H5, H7, H9). 3 of these have been involved in past pandemics (H1, H2, H3). Traditional pandemic surveillance has focussed on monitoring antigenic shift, meaning the re-assortment of novel haemagglutinins into seasonal human influenza A viruses during rare events of double infection with seasonal and zoonotic strains. H5, from avian H5N1 influenza, has been the major cause for concern in recent years. However, the 2009 H1N1 zoonotic event demonstrates that even serotypes already encountered in past human pandemics may constitute new pandemic threats. The protein sequence divergence of the 2009 zoonotic H1 from human seasonal influenza H1 is around 20-24%. A similar level of divergence is found between the 2009 H1 and European swine flu. By contrast, its divergence from North American swine flu strains is around 1-9%. Given that the divergence between H1 and its nearest serotype neighbour H2 is around 40-46%, the 2009 H1 may be broadly considered as halfway towards a new serotype. The current situation is one of antigenic pseudo-shift.

The promise and reality of personal genomics

The publication of the highest-quality and best-annotated personal genome yet tells us much about sequencing technology, something about genetic ancestry, but still little of medical relevance. Which country has published the largest per-capita number of personal genomes? The United States, the United Kingdom? Actually, it is Korea. A recent article in Nature by Kim et al. [1] presents the genome sequence of a Korean male, AK1 - the seventh published sequence of an individual human genome and the second from Korea. The rapid progress in personal genome sequencing is possible because so-called 'next-generation' sequencing technology has decreased costs by orders of magnitude and increased throughput. But those advantages come at a price: short, error-prone reads derived from single molecules that have to be stitched back together to make a best-guess at the starting sequence. We are still at the stage of working out how to apply the available technologies to coax out biological information: the goal of a US$1,000 genome providing life-changing personal medical insights is still some way off.

Obesity: The Integrated Roles of Environment and Genetics

Obesity represents one of the most serious global health issues with ;310 million people presently affected. It develops because of a mismatch between energy intake and expenditure that results from behavior (feeding behavior and time spent active) and physiology (resting metabolism and expenditure when active). Both of these traits are affected by environmental and genetic factors. The dramatic increase in the numbers of obese people in Western societies reflects mostly changing environmental factors and is linked to reduced activity and perhaps also increased food intake. However, in all societies and subpopulations, there are both obese and nonobese subjects. These differences are primarily a consequence of genetic factors as is revealed by the high heritability for body mass index. Most researchers agree that energy balance and, hence, body weight are regulated phenomena. There is some disagreement about exactly how this regulation occurs. However, a common model is the ‘‘lipostatic’’ regulation system, whereby our energy stores generate signals that are compared with targets encoded in the brain, and differences between these drive our food intake levels, activity patterns, and resting and active metabolisms.

Cuts, Rules Threaten Flu Vaccine Program

The U.S. government is expecting delivery starting this week of enough doses of the new swine-flu vaccine for nearly every American who wants it, but state and local budget cuts coupled with limits on who can administer the vaccine could hamstring the campaign. A second wave of the new flu, known as the 2009 H1N1 virus, is widespread across more than half of U.S. states, but it will be weeks before millions of people who want shots can get them. Manufacturers are still producing the 250 million doses the government has ordered, and state health officials must then determine where to distribute them.

Effects of Caffeine on Human Health

The literature suggests that the following effects on behavior of adult humans may occur when individuals consume moderate amounts of caffeine. (1) Caffeine increases alertness and reduces fatigue. This may be especially important in low arousal situations (e.g. working at night). (2) Caffeine improves performance on vigilance tasks and simple tasks that require sustained response. Again, these effects are often clearest when alertness is reduced, although there is evidence that benefits may still occur when the person is unimpaired. (3) Effects on more complex tasks are difficult to assess and probably involve interactions between the caffeine and other variables which increase alertness (e.g. personality and time of day). (4) In contrast to the effects of caffeine consumption, withdrawal of caffeine has few effects on performance. There is often an increase in negative mood following withdrawal of caffeine, but such effects may largely reflect the expectancies of the volunteers and the failure to conduct “blind” studies. (5) Regular caffeine usage appears to be beneficial, with higher users having better mental functioning. (6) Most people are very good at controlling their caffeine consumption to maximise the above positive effects. For example, the pattern of consumption over the day shows that caffeine is often consumed to increase alertness. Indeed, many people do not consume much caffeine later in the day since it is important not to be alert when one goes to sleep. In contrast to effects found from normal caffeine intake, there are reports that have demonstrated negative effects when very large amounts are given or sensitive groups (e.g. patients with anxiety disorders) were studied. In this context caffeine has been shown to increase anxiety and impair sleep. There is also some evidence that fine motor control may be impaired as a function of the increase in anxiety. Overall, the global picture that emerges depends on whether one focuses on effects that are likely to be present when caffeine is consumed in moderation by the majority of the population or on the effects found in extreme conditions. The evidence clearly shows that levels of caffeine consumed by most people have largely positive effects on behavior. Excessive consumption can lead to problems, especially in sensitive individuals.

Gut Microbiota and its Possible Relationship With Obesity

Obesity results from alterations in the body’s regulation of energy intake, expenditure, and storage. Recent evidence, primarily from investigations in animal models, suggests that the gut microbiota affects nutrient acquisition and energy regulation. Its composition has also been shown to differ in lean vs obese animals and humans. In this article, we review the published evidence supporting the potential role of the gut microbiota in the development of obesity and explore the role that modifying the gut microbiota may play in its future treatment. Evidence suggests that the metabolic activities of the gut microbiota facilitate the extraction of calories from ingested dietary substances and help to store these calories in host adipose tissue for later use. Furthermore, the gut bacterial flora of obese mice and humans include fewer Bacteroidetes and correspondingly more Firmicutes than that of their lean counterparts, suggesting that differences in caloric extraction of ingested food substances may be due to the composition of the gut microbiota. Bacterial lipopolysaccharide derived from the intestinal microbiota may act as a triggering factor linking inflammation to high-fat diet–induced metabolic syndrome. Interactions among microorganisms in the gut appear to have an important role in host energy homeostasis, with hydrogen-oxidizing methanogens enhancing the metabolism of fermentative bacteria. Existing evidence warrants further investigation of the microbial ecology of the human gut and points to modification of the gut microbiota as one means to treat people who are overweight or obese.