University College London

A molecular cardiologist looks into getting to the heart of his inner fish.

Newts do it, fish do it, but sadly humans and other mammals cannot repair or regenerate damaged heart tissue as adults.

Despite the modern-day promotion of healthier lifestyles (such as bans on smoking in public places and pro-fitness campaigns in the run-up to London 2012), cardiovascular disease is still on the up worldwide and, not unlike swine flu, is a true pandemic that respects no borders. As a result, and for some time now, I and others have been asking how we might become more newt-like or fish-like and repair our own hearts after a heart attack.

We have favoured looking at small resident progenitor cells which, when stimulated, might make new heart muscle and blood vessels. But a study by Bernhard Kühn and his colleagues at the Children's Hospital Boston in Massachusetts shows us another way (K. Bersell et al. Cell 138, 257–270; 2009).

They simply asked whether or not existing heart muscle can be instructed to divide and make more of the same. Apparently it can, with the help of the epidermal growth factor neuregulin (famed for its role in the nervous system), and its Erb4 receptor. While under the influence of neuregulin, some mature heart cells in mice disassemble their scaffold, re-enter the cell cycle, divide and regenerate injured muscle.

Of course, the devil is in the detail: the trick, it seems, is to have not only plenty of neuregulin, but also more heart muscle cells with one nucleus instead of two, because only the former responded to the growth factor. Unfortunately, this presents something of a conundrum where mammals are concerned. Mammalian heart-muscle cells generally become binuclear shortly after birth. Thus, for a complete fix, we are left heading back in the direction of the drawing board.

Posted by Brendan Maher at 10:18 PM | Permalink | Comments (3) | TrackBacks (0)

Department of Geology, University of Oviedo, Spain

A biogeochemist sees the value of diversity in a changing ocean.

Ocean acidification in response to excess carbon dioxide in the atmosphere could become a problem for marine organisms, especially those that make skeletons or shells out of calcium carbonate. Corals and clams are at risk, as are the coccolithophorids — microscopic algae that are, by volume, the most important shell producers.

These algae have been the guinea pigs in a series of lab studies measuring their response to acidified seawater. But I worry about whether these studies give us an accurate picture of the future. They typically start with clones — descendants of a single cell — grown in acidified conditions for only a few weeks. This set-up precludes the kind of natural selection and adaptation that might occur over decades and centuries in the ocean.

To cloud the waters further, different labs often obtain conflicting results on the same species, a situation some attribute to subtle differences in methods. Fortunately, a recent study by Gerald Langer of the Autonomous University of Barcelona in Spain and his colleagues provides a more satisfying and ultimately more optimistic explanation (G. Langer et al. Biogeosci. Discuss. 6, 4361–4383; 2009). These reserachers grew four different strains of a calcifying algae, Emiliania huxleyi, at different seawater pH levels, and showed that the response to acidification varies significantly among the strains. They argue convincingly that these diverse responses have a genetic basis.

Identifying diverse responses among strains of a species puts us one step closer to capturing the true potential of adaptation in this group of organisms. It would be naive to assume that this puts coccolithophorids out of harm's way. However, diversity is good insurance in a changing ocean. Moreover, I am hopeful that scientific experiments are starting to take that into account.

Posted by Brendan Maher at 05:11 AM | Permalink | Comments (0) | TrackBacks (0)

Center for Insect Science, University of Arizona

An evolutionary biologist learns how to be remembered: cheat someone.

What makes someone unforgettable? Is it their charm? Their looks? Or is it that they once stiffed you on the bill?

Like many others, I have trouble remembering people's names, even as I am being introduced to them, but certain names remain etched in my mind forever. Few, for example, will forget Bernard Madoff, the New York financier convicted of defrauding people out of billions of dollars in a giant Ponzi scheme.

Raoul Bell and Axel Buchner at the Institute of Experimental Psychology in Düsseldorf, Germany, have explored this bias in memory (R. Bell and A. Buchner. Evol. Psychol. 7, 317–330; 2009). They reveal that humans have a greater propensity to remember the names of individuals associated with cheating than names associated with trustworthiness or other unrelated behaviours.

Cooperation is immensely beneficial to humans, but with cooperation looms the ever-present risk of exploitation. Researchers have proposed that humans have a specialized brain module dedicated to detecting and remembering cheaters, to help them to steer clear of future interactions with such individuals. It has previously been suggested that the cheater memory module is tied only to facial stimuli. But using the same behaviours associated with facial stimuli in previous studies, Bell and Buchner were able to replicate these findings using only names, which suggests a more general module for remembering cheaters.

Associating reputations with names is crucial to maintaining social norms through verbal mechanisms such as gossip. Thus memory bias for the names as well as the faces of cheaters could expand the ability of groups of individuals to avoid exploitation.

Madoff probably won't have much luck if he tries to scam people again.

Posted by Brendan Maher at 01:04 PM | Permalink | Comments (0) | TrackBacks (0)

The University of Manchester, UK

A systems biologist ponders how disparate ideas can sometimes come together beautifully.

If X alone and Y alone cannot explain a phenomenon, sometimes together they can. As the late biochemist Henrik Kacser remarked: "To understand the whole you must look at the whole."

Prion diseases, for example, are closely associated with the conformational change of the prion protein PrP from its normal form to an aggregating, autocatalysing, pathologic form, PrPSc. But clumping prions don't tell the whole story. Their levels often correlate poorly with disease progression, and it is far from clear how a simple conformational change leads to the holes in brain tissue seen in late-stage disease.

It is also clear that poorly liganded iron is highly neurotoxic, mainly because it can spur the production of the highly reactive and toxic hydroxyl radical OH* — heavily involved in the progression of many other degenerative diseases and ageing. Neena Singh at Case Western Reserve University in Cleveland, Ohio, and her colleagues have now tied these two disparate threads together.

PrPSc, they found, can sequester cellular iron in insoluble PrPSc–ferritin complexes, making it bio-unavailable, leading to increased iron uptake and an overall excess of iron in brain tissue (A. Singh et al., PLoS Pathog. 5, e1000336; 2009). Modified iron metabolism is found in both scrapie and sporadic Creutzfeldt–Jakob disease, and such work stresses that it is not only the total amount of Fe(II) and Fe(III) that matters but their speciation. It is yet to be shown whether PrPSc–ferritin complexes catalyse OH* production directly, but if they do, this could account for the massive damage observed. Recognition of this could have a colossal effect on our thinking and provide new therapeutic (and dietary) options based on iron chelation for these and other syndromes.

Posted by Brendan Maher at 07:49 PM | Permalink | Comments (0) | TrackBacks (0)