HIV/AIDS Money Matters
Special Online Collection

Over the past decade, funding for HIV/AIDS research and treatment in low- and middle-income countries has exploded, jumping more than 20-fold to $10 billion last year. In a special section of the 25 Jul 2008 issue, Science followed the money trail, with News correspondent Jon Cohen reporting on how the billions research dollars have been divvied up and what they have accomplished. One report looked at the global distribution of funds, another at investments and grants backed by the U.S. National Institutes of Health, and two case studies (with accompanying videos documentaries) highlighted efforts to combat corruption in Uganda and aggressive treatment and prevention programs in Botswana. In addition, a pair of Perspectives examined the progress and challenges of microbicide and HIV vaccine research, an Editorial discussed the particular difficulties of combatting HIV/AIDS in Latin America and the Caribbean, and podcast interviews discussed trends in research funding and the future of vaccine research.


Genetic Clues to Autism

Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication and by repetitive, stereotyped, and obsessive-compulsive behaviors. The underlying causes of autism are unclear, but likely involve diverse and complex genetic factors. In a Research Article in the 11 Jul 2008 Science, Morrow et al. used homozygosity mapping -- which involves analysis of families in which parents of affected individuals share a common ancestor (e.g., first cousins) -- to identify recessive genes that correlate with susceptibility to autism (see the related Perspective by J.S. Sutcliffe). By analyzing the inheritance of DNA through the genome in these pedigrees, the researchers identified several chromosomal regions inherited in common by affected individuals, some of which contained large deletions. The largest deletions implicate genes whose level of expression changes in response to neuronal activity, a marker of genes involved in synaptic changes that underlie learning and memory. These findings suggest that defective regulation of gene expression after neural activity -- and thus disrupted synaptic development -- may be a mechanism common to seemingly diverse autism-associated mutations. Senior author Christopher Walsh discussed the work in a related podcast interview.


Serotonin and Sudden Death

Sudden infant death syndrome (SIDS) is the leading cause of death during the first year of life in developed countries. Postmortem studies have shown deficits in serotonin neurotransmission in the brainstem of afflicted infants, but the mechanism by which such a deficiency might cause sudden death is unknown. In a Report in the 4 Jul 2008 Science Audero et al. reported that in young mice, expression of higher-than-normal levels of a type of serotonin receptor (serotonin receptor 1A or Htr1a) causes sporadic death with features reminiscent of SIDS. In mammals, normal levels of serotonin neuron firing are maintained by negative feedback inhibition via the Htr1a receptor: serotonin that is released locally binds to the receptor located on the same cells that produce the serotonin, and thereby inhibits further serotonin release. The researchers found that mice overexpressing Htr1a showed decreased serotonin firing and exhibited decreased heart rate and hypothermia, sometimes leading to death, during a limited window of time during their development. These results suggest that altered serotonin homeostasis is sufficient to cause autonomic crises and sudden death in mice and that this animal model may help identify new ways to diagnose and prevent SIDS. Senior author Cornelius Gross discussed the findings in a related podcast interview.


Deadly Defiance
Introduction to Special Issue

Almost as soon as penicillin was introduced in 1942, the bacteria it was designed to defeat began evolving to resist it. Now many common bacteria have acquired resistance to multiple antibiotics, making some infections immensely difficult -- if not impossible -- to treat. A special section of the 18 Jul 2008 Science explored the issue of drug resistance and some of the options available for intervention. One news story chronicled the rise and spread of so-called bad bugs, and possible strategies to curb drug resistance given the dearth of new antibiotics in the pipeline. Another story highlighted efforts by the Boston nonprofit organization Partners in Health to tackle the growing threat of multidrug-resistant tuberculosis in places such as Siberia, where resources are limited. Two Perspectives discussed the evolution of antibiotic resistance genes in bacteria in natural environments and whether these might offer clues for fighting infection in clinical settings, and the prospects for outwitting multidrug resistance to antifungals. A special podcast covered themes of the special issue including the ever-escalating war between humans and microbes, how changes in natural ecosystems may be altering microorganism resistance, and the particular challenges of dealing with pathogenic fungi.


Origins of Vertebrate Vocalization

Vocalizations that impart social and environmental information are common to a variety of vertebrates other than humans, including birds, frogs, and even fish. Did the neural structures for soundmaking among this broad group of animals arise from a single common ancestor? In a Report in the 18 Jul 2008 Science, Bass et al. addressed this question by examining the organization of neural circuitry underlying vocalization in larval Batrachoidid fish (midshipman and toadfish), the adults of which use hum, grunt, and buzz noises to attract mates and to stake out territory (see the related ScienceNOW story by D. Malakoff). The team discovered that a set of rhythmically firing motor neurons control the fish’s vocal muscles and the pitch and duration of its calls and that these neurons grow at the base of the hindbrain and the upper part of the spinal cord. Moreover, this vocal circuitry is remarkably similar in location and function to brain structures found in other vertebrates that vocalize, including birds, amphibians, and mammals, suggesting that the neural basis of vocalization originated in a common ancestor of modern vertebrates. An accompanying Perspective by D. Margoliash and M.E. Hale discussed the findings.


Threatened Reefs

Coral reefs harbor the highest concentration of marine biodiversity, but face increasing threats at local and global scales -- from human disturbances such as pollution, sedimentation, and overfishing to elevated sea surface temperatures and ocean acidification caused by the buildup of carbon dioxide and other greenhouse gases in the atmosphere. In a Report in the 25 Jul 2008 Science (published online 10 Jul) Carpenter et al. surveyed 704 reef-building coral species and rated them according to the International Union for Conservation of Nature (IUCN) standards of extinction risk, which rely primarily on population size reduction and geographic range information. About one-third of the species fall into the threatened or near-threatened categories, and are considered at increased risk for extinction. The analysis also shows that the proportion of corals threatened with extinction has increased dramatically over the past decade and exceeds that of most terrestrial animal groups apart from amphibians. The Caribbean and the "Coral Triangle" in the western Pacific have the largest proportion of corals at high risk. The results emphasize the widespread plight of coral reefs and the continued need for conservation measures. A related ScienceNOW story by P. Berardelli published on 10 Jul highlighted the study.


Publishing and Citing Online

Millions of scholarly articles have migrated online in recent years, a development that has made trips to library "stacks" almost obsolete. In a study reported in the 18 Jul 2008 Science, Evans investigated how the wealth of available research afforded by electronic publishing has affected authors’ citation behavior and breadth of scholarship. Using a database of 34 million articles with citations from 1945 to 2005, Evans showed that as more journal issues came online, citation patterns indeed shifted with researchers referencing more narrowly, citing fewer and more recent references than in the past. The trend likely reflects the shift from browsing in print to searching online -- which facilitates avoidance of older and less relevant literature -- as well as the use of hyperlinks within online articles, which puts experts in touch with consensus about the most important prior work on a particular topic. On the flip side, the results indicate that a smaller number of articles than in the past are garnering citations and that valuable papers might end up getting lost in the archives. An accompanying News story by J. Couzin noted that the new results contrast with those from some other studies showing that scientists are actually reading older articles and reading more broadly than before.


MESSENGER Returns to Mercury
Introduction to Special Issue

Mercury is the closest planet to the Sun, and the smallest of the inner planets of our solar system. It is also the only inner planet other than Earth to have an internal magnetic field. Most of what we know about this unusual planet comes from observations from the Mariner 10 spacecraft captured in the mid-1970s and ground-based studies. In a special section of the 4 Jul 2008 Science, a series of Reports detailed new observations by the Mercury Surface, Space Environment, Geochemistry, and Ranging (MESSENGER) spacecraft, which flew by Mercury in January 2008 and after two more passes, will settle into orbit around the planet in 2011. The broad range of observations made during the flyby illuminate the strongly dynamic interactions among Mercury’s interior, surface, tenuous atmosphere, and magnetosphere. Surface observations made by several instruments reveal that volcanic activity and impact processes have been important in shaping the planet and indicate that Mercury has actually contracted over its history as a result of cooling of its mantle and core. Principal investigator of the MESSENGER mission Sean Solomon discussed these and other findings in a related podcast interview.


Improving Solar Cells

Photovoltaic concentrators aim to increase the electrical power obtained from solar cells. Conventional devices rely on large mobile mirrors to track the Sun during the day, but these mirrors are expensive to deploy and maintain and require that the solar cells at the focal point of the mirrors be cooled. One alternative is to use luminescent solar concentrators, waveguides in which dye molecules absorb incident light and then reemit at wavelengths that are collected by attached solar cells. But their performance has so far been limited because much of the extra light collected is lost via reabsorption by the dye. Now, in a Report in the 11 Jul 2008 Science, Currie et al. describe a next-generation "organic solar concentrator" that consists of a piece of transparent glass with a thin film of dye molecules deposited on the face and inorganic solar cells attached to the edges. Light is absorbed by the dye coating and reemitted into the glass for collection by the solar cells. In order to avoid the problem of light loss, the team added a small concentration of second dye that collects all the absorbed light from its surrounding dye molecules. They also made use of phosphorescent dyes, which only weakly absorb their own emitted light. These and other technical innovations improved solar cell efficiency 10-fold.


Marine Diversity Revisited

Early analyses of past marine diversity have suggested a steep increase in the diversity of marine invertebrates during the Cretaceous period and Cenozoic Era, particularly since about 100 million years ago. In a Research Article in the 4 Jul 2008 Science, Alroy et al. presented the a new curve of marine diversity based on a combing of the most recent version of the Paleobiology Database -- a compilation of about 3.5 million specimens with individually recorded ages and geographic coordinates that spans the last 500 million years. Their analysis employs sampling standardization and more robust counting methods than previous efforts and shows only a modest rise in diversity largely confined to the Jurassic and Early Cretaceous. This suggests that something has been constraining evolution and diversity for hundreds of millions of years -- perhaps some type of bottleneck in the way energy moves up through the food chain. A related News story by R.A. Kerr noted that it is also possible that young fossils found in loose sediment that were excluded from the analysis may have damped the plotted rise.


Tracking Corrosion Cracking

During fabrication and operation, many stainless steel components are exposed to mechanical loads that create high strains inside the material. This stress, combined with exposure to environmental damage such as that caused by corrosion, can lead to mechanical failure. In a Report in the 18 Jul 2008 Science, King et al. offered insight into the microscopic origin of environmental corrosion by studying crack formation in situ. The team used diffraction contrast tomography -- a nondestructive three-dimensional mapping technique -- to image grain shapes and their crystal orientation in a stainless steel wire. When the metal was exposed to a corrosive environment, the researchers observed that special grain boundaries were resistant to the cracking process due to the formation of bridging ligaments that retain some ductility within the material. As noted in an accompanying Perspective by A. Stierle these results suggest that "[t]he development of better types of stainless steel will require simultaneous improvement of the mechanical properties and corrosion resistance via grain boundary engineering…"



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In Science Signaling

New Paradigm for Fighting Infection

The current strategy for managing infectious diseases has focused mainly on targeting unique processes or enzymes within pathogens with specific drugs. A major disadvantage of this pathogen-directed drug targeting approach has been the development of microbial drug resistance and consequent resurgence of once-contained infectious diseases. In a Review in the 22 Jul 2008 issue, A. Schwegmann and F. Brombacher discussed the emergence of a new drug discovery paradigm that focuses on identifying and targeting host factors essential for pathogen entry, survival, and replication. Fueling this new approach are innovative strategies that combine genome-wide computational biology, genomics, proteomics, and traditional forward and reverse genetics to identify host-pathogen interactions and host functions critical for the establishment of infection. Most host-directed drug targeting studies have so far focused on viral infections, but they have provided a proof of concept for similar approaches to bacterial and parasite infections. The authors note that "[f]uture therapies may combine conventional targeting of microbial virulence factors, together with host-directed drug therapy and augmentation of protective host factors, to efficiently eliminate the invading pathogen.

Also in Science Signaling this month:
--J.F. Foley and A.M VanHook, in a podcast, discussed how macrophages might be manipulated to become more efficient killers of tumor cells and bacteria (15 Jul 2008)
--D.D. Carson discussed the numerous roles that the cytoplasmic domain of mucin 1 (MUC1) plays in intracellular signaling pathways (8 Jul 2008)
--A. Atfi and R. Baron explained that interactions between p53 and Smad proteins influence the responses to the transforming growth factor beta pathway, which may be important for progression of some types of cancer. (1 Jul 2008)