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Glee for Glia
Special Online Collection
Years of thorough research have confirmed that glia are highly complex cells engaged in a plethora of functions -- not simply the glue that holds nerve cells together. As described in a special section of the 5 Nov 2010 Science, glial cells are involved in the rapid conduction of action potentials, synapse formation and maturation, as well immune processes in the nervous system. Review articles discussed the growth and development of two subsets of glial cells, astrocytes and myelin-forming oligodendrocytes, while a Perspective outlined the involvement of microglia in the treatment of higher brain functional defects. In the research section of the magazine, a Report investigated the developmental origin of microglia and a Research Article showed that the tonic release of the neurotransmitter GABA in the cerebellum occurs through an anion channel in glial cells. Complementing Science's special section, the 9 Nov issue of Science Signaling highlighted glial cell function, development, and disease, drawing attention to the molecular mechanisms of drug resistance of a cancer of glial origin, and on signaling between glia and neurons.
Cooperative Forest Management
Sustainably managing common natural resources, such as fisheries, water, and forests, is essential for our long-term survival. Conventional analysis assumes that groups struggle to manage common natural resources because of free-riders and people who will maximize short-term self-benefits at the expense of long-term sustainability (the so-called "tragedy of the commons"). However, behavioral laboratory experiments have shown evidence that "conditional cooperation" -- individual cooperation contingent upon the cooperation of others -- can produce shared, long-term benefits. In a Report in the 12 Nov 2010 Science, Rustagi et al. now extend these results to field studies involving Ethiopia's Oromo people, who have been given the authority to use and manage their forests as common property resources. To explore the role of cooperation in this effort, the team analyzed a set of 49 groups, comprising 679 individuals, and gathered data about their propensities to cooperate, socioeconomic backgrounds, and how they monitored their shared resources. Comparing these data to measures of forest productivity, the researchers found that the groups with larger proportions of conditionally cooperative members were more successful in managing their forest commons. Enforcing this cooperation, through costly and time-intensive patrolling of the forests, was the key to productivity. A Perspective by B. Vollan and E. Ostrom highlighted the study.
How Cats Lap
We all know that domestic cats lap milk, but perhaps fewer of us have thought about how they do this. In a Report in the 26 Nov 2010 Science (published online 11 Nov) Reis et al. used high-speed imaging and theoretical analysis to show that the domestic cat laps by a subtle mechanism that exploits fluid inertia to defeat gravity. By first lowering its tongue to touch the liquid surface and then rapidly pulling it up, a liquid column is created, the top of which the cat captures in its mouth before gravity draws it down (see the related video showing a cat lapping in slow motion and a physical model of the process that employs water and a glass disk). Measurements of lapping frequency in domestic and wild cats suggest that this mechanism is conserved among felines and that lapping frequency is tuned to maximize the ingested volume per lap depending on the animal's mass. The subtlety of the process is particularly remarkable, given the tongue's lack of skeletal support. A related ScienceNOW story by G. Telis noted that feline lapping could give "soft" robotics experts a new way to approach problems that require delicate of handling of liquids.
Supersonic jets of energized charged particles have been observed emanating from a variety of astrophysical objects, including supermassive black holes in the centers of galaxies, gamma-ray bursts, planetary nebulae, and brown dwarfs. Despite their different physical scales (from hundreds to billions of astronomical units), these jets share common features, like a gaseous disk around the central object, but whether a universal mechanism can explain the origin of all of these jets has been unclear. In a Report in the 26 Nov 2010 Science, Carrasco-González et al. presented observations of a jet emanating from yet another source -- a young stellar object known as HH 80-81. Radio data captured by the Very Large Array radio observatory indicate that the jet is magnetized and has characteristics that are similar to those of jets found in much larger systems. These results support the idea that all astrophysical jets are launched and collimated through the same basic mechanism, involving launching of material along magnetic field lines. An accompanying Perspective by T. Ray highlighted the findings and their importance for understanding the mechanisms of jet formation.
The Power Behind P450
Drugs, toxins, and a range of metabolic substrates are detoxified in the liver by a family of iron-containing enzymes called cytochrome P450s, which can oxidize normally unreactive carbon-hydrogen bonds. Interest in these enzymes stems not only from their obvious medical and biological importance, but also from a desire to harness their synthetic potential. Chemists have known that the principle intermediate in P450 catalysis is a heme iron bearing a single oxygen atom, but its exact structure has eluded scientists for decades. Now in a Research Article in the 12 Nov 2010 Science, Rittle and Green have used a variety of spectroscopic tools to characterize this long-sought intermediate, which the team captured by freezing a solution of a P450 enzyme from a heat-loving microbe as it reacted with an oxidant. Their analyses, which included structural and kinetic studies, revealed an iron-oxo-porphyrin cation radical intermediate that passes its oxygen along to the substrate with remarkable speed. A related Perspective by S.G. Sligar discussed the study in the context of previous advances in understanding P450 chemistry.
Maximum Mammal Size
For the first 140 million years of their evolutionary history, mammals were small (ranging from about 3-5 g to 10-15 kg) and occupied a fairly narrow range of ecological niches. However, the disappearance of dinosaurs following the end-Cretaceous mass extinction (about 65 million years ago), opened the door for the subsequent diversification of terrestrial mammals, both in size and range. In a Report in the 26 Nov 2010 Science, Smith et al. examined how the maximum size of mammals increased during their radiation using fossil data and measurements of animals from each taxonomic order, on each continent, over their entire evolutionary history. Their analysis reveals that overall, mammal size increased rapidly and then leveled off after about 25 million years. This pattern holds true on most of the continents, although data are sparse for South America. The analysis also suggests that the primary drive for the evolution of large mammals was diversification to fill ecological niches, but that environmental temperature and land area may have ultimately constrained the maximum size achieved.
Erasing Fear Memory
Traumatic fear memories can be inhibited by behavioral therapy for humans, or by "extinction" training in rodents, but are prone to recur. Under some conditions, however, these treatments generate a permanent effect on behavior, which suggests that emotional memory erasure has occurred. In a Report in the 19 Nov 2010 Science (published online 28 Oct), Clem and Huganir shed light on the neural basis of this fear erasure. Using a combination of electrophysiology and behavioral training in mice, the team observed that fear conditioning (the process by which the animals learn to be afraid of a given stimulus) increases synaptic transmission by calcium-permeable glutamate receptors known as AMPARs into the amygdala -- the part of the brain that controls emotional responses. This effect lasted for about a week, during which the fearful memories could be erased if the animals were then trained to reduce the conditioned fear responses. Postmortem brain slices confirmed that the synaptic changes acquired during fear conditioning were actually reversed in mice that had undergone fear extinction training during this week-long window of opportunity. These results reveal a molecular mechanism for fear erasure and the relative instability of recent memory -- findings that could be useful for interventions to alleviate traumatic memories.
MRI and Microfluidics
In the hospital and laboratory alike, magnetic resonance imaging (MRI) routinely provides detailed information about the interior structure and chemistry of objects and tissues. However, its applications are ultimately limited by the need to enclose the specimen within a detection coil; acquiring an image with increasingly smaller pixels reduces the sensitivity. In a Report in the 19 Nov 2010 Science, Bajaj et al. described a technique that overcomes this limitation by means of remotely detected MRI, thus enabling sensitive measurements of fluid flowing through microfluidic, "lab-on-a-chip" (LOC) devices. LOC devices consist of networks of channels, chambers, and valves with features that range in size from hundreds of nanometers to a few millimeters. Because they require very small volumes of samples and reagents and create a closed system that minimizes the risk of contamination, LOC devices have become an attractive technology for use in forensic science, environmental analyses, and medical diagnostics. The new technique, which records magnetic resonance signals from the spent fluid that exits the device, could be useful for tailoring chips for diagnostics or for imaging fluids flowing through porous materials or the body's tiniest blood vessels. An accompanying Perspective by M. Utz and J. Landers discussed the technique in further detail.
Aside from prions -- which can trigger a cascade of protein misfolding associated with "mad cow disease" and Creutzfeldt-Jakob disease -- there has been no evidence that other neurodegenerative diseases associated with protein misfolding are transmissible between humans by an infectious agent. But in a Report in the 12 Nov 2010 Science, Eisele et al. showed that mouse brain extracts containing aggregates of beta-amyloid, the peptide that induces formation of debilitating brain plaques in Alzheimer's disease, can cause plaque-associated pathological changes in the brains of recipient mice when injected into other parts of their body. This finding extends previous work showing that beta-amyloid extracts can induce plaque formation if injected directly into the mouse brain -- and it has implications for a pathogenic mechanism reminiscent of prion transmission. Although the transport mechanism from peripheral tissue to the brain is unclear, an accompanying Perspective by J. Kim and D.M. Holtzman noted that the possibility of cell-to-cell passage of misfolded proteins could open the door to new treatment strategies for their associated disorders, such as antibodies or small molecules that block transmission of the protein.
Positronic Atomic Physics
According to our current understanding of nature, every charged particle has an antimatter counterpart of the same mass but opposite charge. Positronium (Ps), the atom formed from an electron and its antiparticle the positron, is the lightest neutral atomic species. Its interaction with matter is used to shed light onto fundamental physics, probe material defects, and perform dynamic imaging of metabolic pathways through positron emission tomography (PET). Since positronium lives long enough to scatter off other matter before decaying, researchers involved in such disciplines need to understand its scattering properties. In a Brevium in the 5 Nov 2010 Science, Brawley et al. reported the surprising finding that despite positronium being neutral and twice the mass of an electron, it scatters as if it were just a free electron. This result implies that the positron's interaction with the target is somehow "cloaked." An accompanying Perspective by H. R. J. Walters discussed how further understanding of the properties of Ps atoms could be a gateway to the ambitious project of making a stable form of antihydrogen -- the bound state of an antiproton and a positron -- which would allow scientists to test fundamental theories of relativistic quantum mechanics.
In Science Signaling
Making Resistance Futile
Mutations in the BRAF proto-oncogene are found in many tumor types, including melanomas, thyroid cancers, and colorectal cancers. Drugs that inhibit BRAF or the downstream kinase MEK (mitogen-activated or extracellular signal–regulated protein kinase kinase) -- have shown promise as therapies for individuals with BRAF-mutant tumors. Unfortunately, initial promising clinical responses to such targeted therapies are often followed by replapse, as the cancer cells develop resistance to a particular therapeutic agent. In the 23 Nov 2010 issue of Science Signaling, Corcoran et al. explored the mechanisms whereby BRAF-mutant colorectal cancer cells became resistant to an inhibitor of MEK and found that resistance involved amplification of the mutant BRAF gene. Cancer cells resistant to inhibition of either MEK or BRAF alone remained sensitive to the combined inhibition of BRAF and MEK, which suggest that a combinatorial approach could overcome resistance to targeted therapy -- and perhaps prevent it from arising.
Also in Science Signaling this month:
-- Bhardwaj et al. found that transcriptional regulatory networks resemble corporate management structures (2 Nov 2010)
-- Korzeniowski et al. reported findings on the regulation of Orai1 channels by the calcium sensor STIM1 (16 Nov 2010)
-- Zhang et al. determined how human leukocyte antigen I may contribute to transplant rejection; senior author E. Reed discussed the findings in a related podcast (23 Nov 2010)
In Science Translational Medicine
-- Ferrandi et al. and Lanzani et al. described how the antihypertension drug rostafuroxin can correct abnormal sodium pumping and how this understanding of the drug's mechanism points to a genetic signature that can predict whether a patient will respond to the drug (24 Nov 2010)
-- Palanker et al. presented a technique that improves the precision and reproducibility of cataract surgery by way of an image-guided femtosecond laser (17 Nov 2010)
-- Friedman et al. discussed how an infrastructure that enables secure reuse of patient data can speed the progression of new knowledge from bench to bedside (10 Nov 2010)
-- Scott-Van Zeeland et al. reported that children who carry one variant of a brain protein associated with autism exhibit fewer long-range connections between the prefrontal cortex and more posterior brain regions (3 Nov 2010)
Image credits (in order of appearance): Science cover, 5 November 2010/Ben Emery and Sara Mulinyawe; Micaela Pilotto, Roman Stocker and Pedro Reis; Ilia Denisov/S.G. Sligar, Science 330, 924 (2010); P. Huey