Studies reveal the mechanisms behind tumor metastasis and how to stymie it. But primary tumors still get the lion’s share of researchers’ attention.
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Aberrant brain circuitry may amplify cigarette cravings into addiction
Putative aberrant brain circuitry in addiction.
Cues such as the sight or smell of cigarettes can trigger cravings and cigarette use. But cravings can also be influenced by factors such as drug availability and individual self-control. Combining fMRI and a technique called transcranial magnetic stimulation (TMS), Takuya Hayashi et al. (pp. 4422–4427) investigated the neural basis of craving by examining how the human brain’s frontal lobe contributes to cue-induced cravings in smokers under different drug availability conditions. The authors found that subjective cravings increased with the availability of cigarettes, but the effect was eliminated by transiently inactivating a decision-making region of the brain known as the dorsolateral prefrontal cortex (DLPFC). Using fMRI, the authors then determined that the strongest signal associated with cravings was localized to the medial orbitofrontal cortex (mOFC), an area thought to assign value to stimuli and actions. Inactivating the DLPFC, the authors report, attenuated this craving-related signal as well as other signals in the anterior cingulate and ventral striatum, regions associated with transforming value into action. The findings suggest that the DLPFC may incentivize decisions about drug seeking based on knowledge of drug availability, and that aberrant circuitry between the dorsolateral prefrontal and orbitofrontal cortices may underlie addiction, according to the authors. — T.J.
Potential diagnostic tool for river blindness
The parasitic nematode Onchocerca volvulus, which infected more than 25 million people in Africa according to 2008 prevalence estimates, causes the debilitating disease onchocerciasis, or river blindness. Despite the presence of antiparasitic drugs, the elimination of the disease from Africa will require diagnostic methods for monitoring infection in individuals. Daniel Globisch et al. (pp. 4218–4223) identified a biomarker in human urine that reflects the state of infection with O. volvulus. The authors used a technique called liquid chromatography-mass spectrometry to analyze urine from O. volvulus-infected patients and identified a nonprotein compound, abbreviated NATOG, that was enriched six-fold in infected individuals compared with uninfected controls. NATOG is a metabolite of the nematode neurotransmitter tyramine and is generated by a two-step process involving deactivation of tyramine by a chemical modification called N-acetylation in the worm, followed by excretion into the host, where a glucuronic acid moiety is added prior to elimination. In patients undergoing treatment with the antibiotic doxycycline, which targets a bacterial endosymbiont of O. volvulus, levels of NATOG were found to be one-third of those observed in placebo-treated individuals, suggesting that NATOG levels track parasite load. According to the authors, NATOG represents a promising tool in the development of a diagnostic assay for onchocerciasis. — C.B.
Training may help reverse age-related neural slowing
With advancing age, the time needed to respond to sensory input increases, often resulting in difficulties for older adults in perceiving speech, particularly in noisy environments. Samira Anderson et al. (pp. 4357–4362) examined the effects of auditory-based cognitive training on neural timing and auditory perception in two groups of adults between the ages of 55 and 70. One group completed an adaptive computer-based auditory training program designed to improve the speed and accuracy of auditory information processing, and the other was asked to watch a series of educational DVDs and answer multiple-choice questions based on the DVD content. After 40 hours of training over 8 weeks, the group that received auditory training exhibited improved neural timing, memory, processing speed, and ability to perceive speech in background noise, compared with the group without auditory training. Short-term auditory training induced neural plasticity and led to a partial reversal of age-related declines in neural timing in older adults, according to the authors. Auditory training could help older adults manage communication difficulties, such as understanding speech in noisy environments, the authors suggest. — S.R.
Bacterial biofilms disrupt flow in medical and environmental devices
Streamers (red) impeding flow.
Researchers have long sought clues to the basic structure and physiology of biofilms, which are drug-resistant bacterial slimes that coat many moist surfaces on Earth. Bacteria such as Pseudomonas aeruginosa are particularly problematic as they can form biofilms on a variety of surfaces, including medical devices and water filters. Knut Drescher et al. (pp. 4345–4350) found that the flow of nutrients over a rough surface changed the appearance of P. aeruginosa biofilms, leading to the formation of 3D streamers, akin to bacterial dams, in areas of heavy nutrient flow. Over time, the streamers bridged the gaps on the material’s surface and captured flowing bacterial cells, leading to sudden and rapid clogging of the system. The authors inoculated bare-metal medical stents with P. aeruginosa and, within 12 hours, observed the formation of streamers that spanned the gaps in the stents’ wire mesh. Further examination revealed that the proteins, sugars, and lipids—collectively known as extracellular matrix—shed from biofilms in response to nutrient flow formed a sieve that captures cells and other biomass, causing exponential clogging independent of bacterial growth. The findings suggest that biofilm streamers occur widely in nature and could lead to blockages in environmental, industrial, and medical devices, according to the authors. — A.G.
Role of gut microbiota in blood pressure regulation
Fermentation by gut microbes produces short-chain fatty acids (SCFAs), which are absorbed into the blood stream. Jennifer Pluznick et al. (pp. 4410–4415) found that gut microbes may play a role in modulating blood pressure through the action of certain SCFAs on two major SCFA receptors, olfactory receptor 78 (Olfr78) and Gpr 41. The authors found that Olfr78 was expressed in the kidney and mediated the secretion of the hormone renin in response to SCFAs, particularly propionate. When mice were administered propionate, they experienced a large, rapid, dose-dependent drop in blood pressure, and Olfr78 knockout mice were particularly sensitive to the effect, suggesting that Olfr78 raises blood pressure and antagonizes the hypotensive effects of SCFAs. In contrast, mice lacking Gpr41 did not have a hypotensive response to propionate at a dose that caused a robust hypotensive response in wild-type animals, suggesting that Gpr41 helps lower blood pressure in response to propionate. Reducing gut microbiota biomass in Olfr78-knockout mice by treating them with antibiotics led to an increase in their blood pressure, suggesting that propionate produced by gut microbes modulates blood pressure via the Olfr78 receptor. Studying the cross-talk between gut microbes and the renal-cardiovascular system could help better understand and treat hypertension, the authors suggest. — S.R.
An automated system for language reconstruction
An Austronesian language tree (Left) with branches colored according to the most frequent reconstructed sound change shown in the Internation Phonetic Alphabet chart (Right).
Since the late 18th century, historical linguists have used a labor-intensive, manual procedure to reconstruct protolanguages, which gave rise to modern languages. Using information about the sounds and words that appear in modern languages, linguists painstakingly reconstruct ancestral languages, many of which have few preserved written records. Alexandre Bouchard-Côté et al. (pp. 4224–4229) developed an automated system for reconstruction of protolanguages from words that appear in modern languages using a statistical model that analyzes sound changes at the level of basic phonetic units. The authors reconstructed a set of protolanguages from a database of more than 142,000 word forms from 637 Austronesian languages—spoken in Southeast Asia, the Pacific, and parts of continental Asia—and report that 85% of the reconstructions were accurate within one character of manual reconstructions performed by linguists. In addition, the authors used the system to lend support for a longstanding linguistic hypothesis, which holds that sounds crucial to distinguishing words have a decreased likelihood of changing over time. Although the automated system is unlikely to replace linguists’ nuanced manual reconstructions, the authors suggest that it might prove valuable for large-scale reconstructions. According to the authors, the findings represent a step forward in the application of computational methods to linguistics. — P.N.
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