University of Leeds, UK

A cell biologist ponders an outstanding mystery in muscle formation.

Heart and skeletal muscles have a beautiful, almost crystalline structure of repeating contractile units called sarcomeres. The length of these units is precisely regulated along with the lengths of two types of overlapping filament (thick and thin) that they contain. Muscles contract when crossbridges from thick filaments interact with actin in thin filaments. The amount of contraction depends on the length of each filament and how much they overlap.

A thick filament contains exactly 294 myosin molecules — a limit imposed by the giant 'ruler' protein titin. Yet it is not clear what regulates the length of thin filaments. The protein nebulin has been a key candidate: its size corresponds to thin filament length in several species. Puzzlingly, however, in mice with a targeted deletion of nebulin, skeletal muscle thin filaments are the right length, at least at birth. And Ryan Littlefield at the University of Washington in Friday Harbor and his colleagues have now shown that nebulin is too short to be the ruler — its end is located just short of the tips of the thin filaments (A. Castillo et al. Biophys. J. 96, 1856–1865; 2009).

Because of the way in which thick filaments are built, their middles — at the centre of the sarcomere — have no crossbridges. Littlefield and his colleagues suggest that thin filaments, which grow towards the middle of sarcomeres from their edges, stop growing when they reach this 'bare' zone. Intriguingly, this paper also shows that thin filament lengths in different muscles correspond to the length of titin in those muscles. A single titin molecule stretches from the edge to the middle of the sarcomere. If titin modulates overall sarcomere length, and thus the distance to the bare zone in the centre of the sarcomere, this could indirectly regulate thin filament lengths. Maybe the biggest protein known has yet another job.

Posted by Brendan Maher at 06:31 PM | Permalink | Comments (0) | TrackBacks (0)

University of Illinois at Chicago

A neuroscientist argues for a broader approach to brain mapping.

Efforts to map all of the connections between the brain’s neurons — known as synapses — are gathering momentum. Neural ‘wiring diagrams’ have even garnered a label: the ‘connectome’. But I worry that the connectome
will be a waste of time and money, and that we’ll eventually need to redo the whole thing.

Why am I so negative? Although the connectome is ambitious, it’s not ambitious enough. As currently envisioned, it ignores most brain cells as well as possible functional connections between those cells.

Although you wouldn’t know it from all the attention they receive, neurons are a relatively minor type of brain cell, making up less than 10% of the human brain. And synapses between neurons comprise only a small subset of all possible functional connections in the brain. Most brain cells are actually glia, which have long been neglected by neuroscientists owing to their lack of electrical signalling. But glia are increasingly being recognized as having important roles in brain function.

For example, consider the recent study of adenosine and sleep led by Philip Haydon and Marcos Frank at the University of Pennsylvania in Philadelphia (M. M. Halassa et al. Neuron 61, 213–219; 2009). Adenosine binds to receptors on neurons, thereby regulating neuronal signalling. Interestingly, adenosine seems to represent
‘sleepiness’: it accumulates during wakefulness, and dissipates during sleep. Where does it come from? It is generated from adenosine triphosphate (ATP), which is secreted by astrocytes — a major type of glia.

Therefore, if we want to map the functional brain connections controlling sleep, we need to include glia and the extracellular space between glia and neurons. If we’re going to understand brain function by mapping the brain, we need to include most of the brain in our map.

Posted by Brendan Maher at 06:00 PM | Permalink | Comments (1) | TrackBacks (0)

University of Ottawa, Canada

A biophysicist ponders the application of hidden metric spaces to genetic networks.

Complex networks can be conceptualized as a collection of points or 'nodes' connected by edges that represent their interactions. The structure and logic of these visualized networks allows mathematical modelling to investigate dynamics such as how information propagates through a system. I am particularly interested in gene regulatory — ensembles of molecules and interactions that control gene expression — because of their connection to human diseases such as cancer.

Marián Boguñá and his colleagues suggest that real, observable networks are underlain by geometric frames that contain all nodes, influence topology and guide information-routing decisions. They call these underlying frames 'hidden metric spaces' (M. Boguñá et al. Nature Phys. 5, 74–80; 2009).

In addition to the distance between nodes in the observable network, one can measure similarity between nodes — which can be determined by, for example, how many neighbours they share — and abstract it as a 'hidden distance'. Hidden distances are then used to define the hidden metric space that would place similar nodes closer together, increasing the probability that they are connected and interacting in the network.

A major challenge to applying this framework is explicitly identifying the structure of the hidden metric space for complex networks, for which data sets are often noisy or incomplete. For genetic networks, hidden distances could be abstracted from available data such as tissue-expression profiles. Comparing hidden metric spaces constructed from different data types with known genetic interactions would identify which data are best suited to the process. It will be interesting to see what this reveals in terms of the structure and dynamics of genetic networks.

Posted by Brendan Maher at 06:43 PM | Permalink | Comments (0) | TrackBacks (0)

University of Florida, Gainesville

An archaeologist looks at South America's early complex societies.

What leads to the rise and fall of civilizations? In coastal Peru, early urban societies based on maritime fishing thrived from 5,800 to 3,600 years ago. Daniel Sandweiss at the University of Maine in Orono and his colleagues report that climate and environmental changes were critical to the rise of these societies (D. H. Sandweiss et al. Proc. Natl Acad. Sci. USA 106, 1359–1363; 2009). They find that environmental shifts are well recorded in coastal geological features, which correlate to high Andes glacial cores, notably in the sixth millennium BP, when small urban centres also emerged in southwestern Asia – the 'cradle of civilization'. But as the Peruvian coastal embayments disappeared, around 3,600 years ago, so too did the societies that depended on them.

This paper particularly interested me as our work in the southern Amazon has revealed integrated towns and villages thriving several millennia later on similar resources as the early Andeans — fish, fruit and tubers. Although not as marked as coastal Peru, climatic fluctuations recorded in glacial records, notably the 'Medieval Warming' around 1100–1300 ad, coincided with the emergence of these small territorial polities.

The early complex societies of South America prompt debate over what constitutes urbanism and 'civil society' in its earliest and most minute forms,and make us reconsider the traits and typologies developed from classical civilizations and Western experience. Notably, in some South American cases, corporate labour and civic organization were not based on agricultural intensification and administration of crop surpluses.

Whether we call them urban or not, these societies show unique properties of self-organization and dynamics of the relationship of humans with natural systems.

Posted by Brendan Maher at 08:08 PM | Permalink | Comments (0) | TrackBacks (0)

University of Sheffield, UK

A chemist welcomes an ingenious advance in plastics technology.

It's a rare joy to come across a communication that is truly concise, with a genuinely surprising but ultimately logical result, and compellingly modest conclusions that could materially benefit our society. Anne Hiltner at Case Western Reserve University in Cleveland, Ohio, and her colleagues take two well established facts — confined polymers form single crystals, and a blend of polymers, when stretched and folded by clever processing, makes very many thin layers — and use them to make something novel: a two-polymer blend with an oxygen permeability 100 times lower than either of its components (H. Wang et al. Science 323, 757–760; 2009).
Plastics are often used in packaging as multilayer coatings. When each layer is thick, the barrier to oxygen is the sum of the properties of its components. The team found that as the layers were stretched, making them thinner, and folded back on themselves to make many layers, the plastic film became an even better oxygen barrier.
When a polymer crystallizes in a confined film it typically makes large pancake-like crystals around 10 nanometres thick and many micrometres across. Using simple mathematical models, the team showed that the improved barrier properties were due to the stretched and folded polymers forming alternating layers of such crystals. The core of each crystal is essentially impermeable to oxygen, which thus has to go across the pancake to find the edge — and at each alternate layer it faces another impermeable core: like a person having to go 1 kilometre sideways to go 1 metre forwards.
This astounding improvement is essentially free and could be incorporated into current packaging materials at little cost, reducing their environmental and energy impact. It makes a cold beer in a biodegradable plastic bottle a distinct possibility — and for me that would be a rare joy indeed!

Posted by Brendan Maher at 08:53 PM | Permalink | Comments (0) | TrackBacks (0)