Gladstone Institute of Cardiovascular Disease, San Francisco, California

A geneticist wonders why we need to sleep.

Scientists can have a love–hate relationship with sleep. We know that it is vital for our health, but not the reasons why. We celebrate dreams that provide inspiration, but often dismiss sleep as a chore.

Yet deep sleep can provide insight into vexing problems. In 1920, pharmacologist Otto Loewi famously had a recurring dream that suggested how he could demonstrate neurotransmission in the lab. The key experimental details escaped him until he captured the dream in a bedside notebook. Later that day, he performed his Nobel-prizewinning experiments with the aid of a few frog hearts and a water bath.

Now, a team led by Ying-Hui Fu reports that a single mutation in a gene called DEC2 can cause people to sleep for only about six hours per night instead of the usual eight (Y. He et al. Science 325, 866–870; 2009). This mutation seems to be exceedingly rare, with only two carriers found so far. Only by introducing this mutation into transgenic mice and fruitflies could the researchers show compelling evidence of the mutation's effect. These two additional waking hours each day are quite remarkable when you consider that, over 80 years, this would add up to more than 8 years of extra productivity!

Why are extreme short sleepers so rare? Surely evolutionary pressures should favour less sleep? In prehistoric times, short sleepers would have had more time to hunt, gather food and guard against predators. In modern society, we must constantly balance home, work and other demands. Sleep is often sacrificed, so a drug that could provide hours of extra productivity would be hugely popular.

A better understanding of the reasons for sleep could provide a rationale for getting more of it. In the meantime, I will keep a notebook by my bedside as a dream catcher.

Posted by Corie Lok at 08:18 PM | Permalink | Comments (2) | TrackBacks (0)

Keio University School of Medicine, Tokyo, Japan

A biologist praises a mouse model of autism inheritance.

Autism, a neurodevelopmental disorder that affects people's social abilities, has both genetic and non-genetic causes. Chromosomal abnormalities account for 10–20% of autism cases, with duplication of a long stretch of chromosome 15 being the most common. I was excited to read that a mouse model with a similar chromosomal duplication has been generated (J. Nakatani et al. Cell 137, 1235–1246; 2009). These mice exhibit the inflexible behaviour, social abnormalities and increased anxiety often observed in people with autism. However, whereas the engineered mice inherit the duplication from their fathers, human autism cases caused by such a duplication are usually inherited maternally. Further genomic analysis in the mice should find the reason for this discrepancy.

This model deserves special attention as the chromosomal duplication is stably maintained between generations. Also, genes in the duplicated regions seem to work; that is, the expression levels of genes — including HBII52, which affects the function of serotonin, a molecule that has cognitive roles in mood, memory and learning — are higher in the mice, as would be expected with a gene duplication.

Accumulated evidence shows that variations in gene-copy number, such as the chromosomal duplication in this model, are associated with susceptibility to various human diseases; cancer cells, for example, tend to have high gene-copy numbers. Thus, this mammalian model may help us to understand the molecular basis of autism and to investigate the contribution of gene duplication in other genetic diseases. This should encourage many researchers to produce other model systems for copy-number variation using similar techniques; systems that may clarify the contribution of chromosomal duplication, or even the lack of it, in common diseases such as diabetes.

Posted by Corie Lok at 10:56 PM | Permalink | Comments (0) | TrackBacks (0)

Texas A&M University, College Station, Texas

A coastal ecologist sees the hidden effects of hurricanes.

As part of my job, I often drive around looking at the impacts of hurricanes in coastal areas. The one thing that stands out from such trips is that the devastation always looks the same, regardless of where I am — the boats perched on the streets, the newly house-less stilts near the beach, the furniture on a lawn covered in mould.

I realized though, after reading a recent article by Hongcheng Zeng of Tulane University in New Orleans, Louisiana and his colleagues (H. Zeng et al. Proc. Natl Acad. Sci. USA 106, 7888–7892; 2009), that I need to be concerned with the damage that I cannot see — the bleeding of carbon from the landscape, and the loss of future carbon stores.

Using field, satellite and modelled data, Zeng and his colleagues detail how damaging winds over the past 150 years have greatly reduced forest biomass through tree mortality, subsequent wood decay and carbon release. They estimate that between 1980 and 1990, 9–18% of the amount of carbon stored yearly by US forests was lost due to destruction caused by tropical cyclones. The carbon dioxide loss is cumulative because once a tree is lost, it cannot sequester CO2 in the future. Thus, an extreme event such as Hurricane Katrina in 2005 or the Indian Ocean tsunami in 2004 could radically reduce carbon sequestration in the areas affected for several decades.

These findings force me to consider more than just the visible effects of hurricanes; I realize that tree loss is in effect altering the global carbon cycle. This paper also makes me wonder about the cumulative impact of cyclones on CO2 in other ecosystems, such as grasslands that have been damaged by salt-water inundation, or even possible forest growth due to storm-induced rainfall inland.

Posted by Brendan Maher at 03:37 PM | Permalink | Comments (0) | TrackBacks (0)

Burnham Institute for Medical Research, La Jolla, California

A biologist is gratified to find reconciliation for a conflicted receptor.

When giving talks on the involvement of the Eph family of receptor tyrosine kinases in cancer, I sometimes include a slide of the two-faced Roman god, Janus, to signify the dichotomies of Eph function in cancer cells. Most proteins have a clear-cut function. Some 'moonlighting' proteins carry out two unrelated functions. It is, however, rare for a protein to toggle between opposing activities. The Eph receptors are proving to be such outliers.

High expression of Eph receptors has been correlated with a poor cancer prognosis, but so has Eph silencing. Accordingly, there is good evidence that the Eph receptors can promote as well as inhibit tumour development. In a reconciliation reminiscent of Hegelian synthesis, a recent paper begins to explain how the EphA2 receptor can both promote and inhibit cancer cells' migratory and invasive abilities.

EphA2 activation by ephrin ligands seems to be minimal in most types of cancer cell. Hui Miao and Bingcheng Wang of Case Western Reserve University in Cleveland, Ohio, and their co-workers have shown that the protein Akt — which can be powerfully cancer-promoting — hijacks EphA2 by phosphorylating one of its serine residues, enabling its pro-metastatic activities (H. Miao et al. Cancer Cell 16, 9–20; 2009).

Remarkably, binding by the ephrin-A1 ligand erases this phosphorylation and transforms EphA2 into an anti-invasive molecule.

These findings lead to the counterintuitive proposition that we should encourage rather than inhibit EphA2's ligand-dependent function. It will be interesting to see whether analogous switches convert other Eph receptors between malignant and benign phenotypes.

Posted by Brendan Maher at 12:38 AM | Permalink | Comments (0) | TrackBacks (0)

Brown University, Providence, Rhode Island

A microbiologist wonders what turns us on.

An Internet search for the words 'pheromone attractant' pulls up products ranging from human aphrodisiacs to control measures for the Colorado potato beetle.

But sexual chemistry is not only important to humans and beetles, it is also relevant to many fungi. Fungal peptide pheromones are often released by one mating type to attract a partner of the opposite sex, thereby initiating the programme of sexual differentiation. This signalling is often highly specific so that pheromones attract only potential partners and not unwanted suitors.

Work by Joseph Heitman and his colleagues at Duke University in Durham, North Carolina, provides a new spin on pheromone signalling in fungi (Y.-P. Hsueh et al. EMBO J. 28, 1220–1233; 2009). While studying the fungal pathogen Cryptococcus neoformans, the authors became curious about the function of an uncharacterized pheromone-receptor-like gene.

It turns out that this gene, CPR2, encodes a constitutively active receptor that stimulates downstream mating events in both the presence and absence of pheromones. During sexual differentiation, expression of CPR2 is upregulated and supplements the activity of conventional pheromone receptors. A single amino-acid substitution in the Cpr2 protein, in a transmembrane domain that is highly conserved among pheromone receptors, was shown to be responsible for constitutive signalling activity.

This demonstrates that the sexual lifestyles of unicellular organisms can be much more complicated than they first seem. Furthermore, constitutively active receptors have been implicated in many signal-transduction processes in mammalian cells. It remains to be seen whether sexual activity in more complex organisms also involves signalling components that are continuously turned on.

Posted by Brendan Maher at 09:35 PM | Permalink | Comments (0) | TrackBacks (0)