Low-frequency variation in TP53 has large effects on head circumference and intracranial volume.

Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for low-frequency variants within TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carriers during mid-childhood, suggesting a previously unrecognized role of TP53 transcripts in human cranial development

Data-driven design of metal-organic frameworks for wet flue gas CO2 capture.

Limiting the increase of CO2 in the atmosphere is one of the largest challenges of our generation1. Because carbon capture and storage is one of the few viable technologies that can mitigate current CO2 emissions2, much effort is focused on developing solid adsorbents that can efficiently capture CO2 from flue gases emitted from anthropogenic sources3. One class of materials that has attracted considerable interest in this context is metal-organic frameworks (MOFs), in which the careful combination of organic ligands with metal-ion nodes can, in principle, give rise to innumerable structurally and chemically distinct nanoporous MOFs. However, many MOFs that are optimized for the separation of CO2 from nitrogen4-7 do not perform well when using realistic flue gas that contains water, because water competes with CO2 for the same adsorption sites and thereby causes the materials to lose their selectivity. Although flue gases can be dried, this renders the capture process prohibitively expensive8,9. Here we show that data mining of a computational screening library of over 300,000 MOFs can identify different classes of strong CO2-binding sites-which we term 'adsorbaphores'-that endow MOFs with CO2/N2 selectivity that persists in wet flue gases. We subsequently synthesized two water-stable MOFs containing the most hydrophobic adsorbaphore, and found that their carbon-capture performance is not affected by water and outperforms that of some commercial materials. Testing the performance of these MOFs in an industrial setting and consideration of the full capture process-including the targeted CO2 sink, such as geological storage or serving as a carbon source for the chemical industry-will be necessary to identify the optimal separation material

Radionuclide imaging of spinal infections

Background: The diagnosis of spinal infection, with or without implants, has been a challenge for physicians for many years. Spinal infections are now being recognised more frequently, owing to aging of the population and the increasing use of spinal-fusion surgery. Discussion: The diagnosis in many cases is delayed, and this may result in permanent neurological damage or even death. Laboratory evidence of infection is variable. Conventional radiography and radionuclide bone imaging lack both sensitivity and specificity. Neither in vitro labelled leucocyte scintigraphy nor 99mTc-anti-granulocyte antibody scintigraphy is especially useful, because of the frequency with which spinal infection presents as a non-specific photopenic area on these tests. Sequential bone/gallium imaging and 67Ga-SPECT are currently the radionuclide procedures of choice for spinal osteomyelitis, but these tests lack specificity, suffer from poor spatial resolution and require several days to complete. [ 18F]Fluoro-2-deoxy-D-glucose (FDG) PET is a promising technique for diagnosing spinal infection, and has several potential advantages over conventional radionuclide tests. Results: The study is sensitive and is completed in a single session, and image quality is superior to that obtained with single-photon emitting tracers. The specificity of FDG-PET may also be superior to that of conventional tracers because degenerative bone disease and fractures usually do not produce intense FDG uptake; moreover, spinal implants do not affect FDG imaging. However, FDG-PET images have to be read with caution in patients with instrumented spinal-fusion surgery since non-specific accumulation of FDG around the fusion material is not uncommon. Conclusion: In the future, PET-CT will likely provide more precise localisation of abnormalities. FDG-PET may prove to be useful for monitoring response to treatment in patients with spinal osteomyelitis. Other tracers for diagnosing spinal osteomyelitis are also under investigation, including radiolabelled antibiotics, such as 99mTc-ciprofloxacin, and radiolabelled streptavidin-biotin complex. Antimicrobial peptides display preferential binding to microorganisms over human cells and perhaps new radiopharmaceuticals will be recruited from the array of human antimicrobial peptides/proteins. In experiments with Tc-ubiquicidin-derived peptides, radioactivity at the site of infection correlated well with the number of viable bacteria present. Finally, radiolabelled antifungal tracers could potentially distinguish fungal from bacterial infections. © 2006 Springer-Verlag.SCOPUS: re.jinfo:eu-repo/semantics/publishe