January 15, 2013 u vol. 110 u no. 3 u 799–1138

Proceedings of the National Academy of Sciences of the United States of America www.pnas.org PNASIn This Issue

PNAS u January 15, 2013 u vol. 110 u no. 3 u 799–800www.pnas.org/cgi/doi/10.1073/iti0313110

In people with retinitis pigmentosa, blindness occurs after a progressive loss of photoreceptor cells destroys the outer nuclear layer (ONL) of the retina. Although transplanted photorecep-tor cells could potentially restore vision in these patients, previous studies have not examined whether transplanted photoreceptors can sur-vive, mature, and reconnect on a degenerate ret-ina that has lost its ONL. Using a murine model of severe human retinitis pigmentosa, Mandeep Singh et al. (pp. 1101–1106) found that trans-planted rod precursors can rebuild an anatomi-cally distinct and appropriately polarized ONL at a stage in disease progression when no host rod cells remain. Newly introduced precursors, the authors report, were able to resume develop-ment in the degenerate host retina, become ma-ture rods with light-sensitive outer segments, and reconnect with host neurons. In addition, assays of mice before and after the procedure revealed that transplantation restored vision even when the animals had no rod function at baseline. The findings, which show that cell replacement therapy in mice reconstitutes a complete and functional light-sensitive ONL, suggest that photoreceptor layer reconstruction might be a viable clinical strategy for retinal repair in humans, according to the authors. — T.J.

Photoreceptor transplantation in mice

Reconstructed light sensitive layer of the retina (green).

Neurological diseases such as multiple sclerosis, Al-zheimer’s disease, and Parkinson disease, compromise the blood–brain barrier, al-lowing the inappropriate pas-sage of molecules and cells into the brain with deleteri-ous effects. Enrico Cristante et al. (pp. 832–841) show that annexin A1 (ANXA1), an anti-inflammatory messenger protein, regulates the integ-rity of the blood–brain barrier in brain microvascular en-dothelial cells. Homozygous ANXA1 knockout mice, the authors report, exhibit sig-nificantly increased permeability of the barrier due to changes in the cytoskeleton that disrupt interendothe-lial cell tight junctions. According to the authors, the

relationship between ANXA1 and neurological disease is supported by earlier studies that have reported a se-

lective loss of ANXA1 in the cerebrovascular endothelium of people with multiple scle-rosis. The authors also found that treating cerebrovascular endothelial cells with human recombinant ANXA1 protein restores cell polarity, cyto-skeleton integrity, and nor-mal tight junction permeabil-ity, by inhibiting a signaling pathway that dysregulates ac-tin cytoskeleton growth and repair. The findings suggest

that ANXA1 acts as a critical regulator of blood–brain barrier integrity and may represent a drug target in mul-tiple sclerosis, according to the authors. — T.J.

Blood–brain barrier integrity in cerebrovascular endothelium

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Comparison of gadolinium extravasation inthe brain of AnxA1-/- and wild-type mice.

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Researchers in the paints and plastics industries have long pursued safe alternatives to inorganic pigments, many of which contain toxic heavy metals. Pigments de-rived from rare-earth elements represent a potential solution, but the computations needed to deduce the materials’ col-ors from a set of basic assump-tions, or first principles, remain challenging. Jan Tomczak et al. (pp. 904–907) use basic knowl-edge about the atomic positions of two rare-earth pigments to compute the red colorations of cerium fluorosulfide (CeSF), a typical rare-earth pigment with a layered ThCr2Si2 struc-ture, and mercury sulfide (HgS), also known as cinnabar

red or vermilion, a conventional semiconductor with a simple hexagonal structure. The authors computed the pigments’ optical absorptions and determined the extent

to which coloration depends on pigment thickness, concentra-tion, and coarseness. Based on their findings that the origin of each pigment’s red coloration differs at the atomic scale, the authors suggest a criterion for quantitatively assessing a pig-ment’s performance. According to the authors, the study dem-onstrates how modern compu-tational methods can provide

powerful tools for the theoretical design of materials with specific optical properties. — A.G.

The past 3 decades have seen a rise in the incidence of dengue, a potentially fatal mosquito-borne viral infection largely prevalent in tropical and subtropi-cal countries. Transmitted by the day-biting mos-quito Aedes aegypti, the disease is hard to combat, partly due to a lack of effective vaccines and anti-viral drugs. While dengue prevention efforts have largely focused on controlling mosquito popula-tions, Steven Stoddard et al. (pp. 994–999) explored whether the movement of infected individuals from house to house influences disease transmis-sion. The authors performed a longitudinal study of dengue transmission among more than 2,400 people in Iquitos, an urban area in northeastern Peru. The authors traced the households visited over a 2-week period by febrile individuals diag-nosed with a dengue infection, and then tested the residents of these households for recent dengue infection. Through 54 such “contact-site cluster” investigations over two transmission seasons, the authors found that infection risk and transmission rates were increased among households visited by dengue-infected people, suggesting that house-to-house movement of people might play a key role in dengue transmission. Human mediated dengue vi-rus dispersal at regional scales has been document-ed, but the findings underscore the role of human movement in disease transmission at a fine spatial scale. Compared with distances covered by hu-man movement between houses, the A. aegypti mosquito has a limited flight range. Thus, the findings might help focus attention on human-mediated virus dispersal in dengue prevention efforts, according to the authors. — P.N.

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Geographic distribution of households in dengue-positive clusterinvestigations. Lines connect contact sites with the homes of index cases.

Human movement influences dengue spread

Computing the color of a rare-earth element

Selective light reflectivity of CeSF.

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