A Tale of Two Methods: Combining Near-Infrared Spectroscopy with MRI for Studies of Brain Oxygenation and Metabolism

Combining magnetic resonance imaging (MRI) with near-infrared spectroscopy (NIRS) leads to excellent synergies which can improve the interpretation of either method and can provide novel data with respect to measuring brain oxygenation and metabolism. MRI has good spatial resolution, can detect a range of physiological parameters and is sensitive to changes in deoxyhemoglobin content. NIRS has lower spatial resolution, but can detect, and with specific technologies, quantify, deoxyhemoglobin, oxyhemoglobin, total hemoglobin and cytochrome oxidase. This paper reviews the application of both methods, as a multimodal technology, for assessing changes in brain oxygenation that may occur with changes in functional activation state or metabolic rate. Examples of hypoxia and ischemia are shown. Data support the concept of reduced metabolic rate resulting from hypoxia/ischemia and that metabolic rate in brain is not close to oxygen limitation during normoxia. We show that multimodal MRI and NIRS can provide novel information for studies of brain metabolism.NSERC; CIHR; endMS; MS Society of Canada; AIHSYe

Zmat3 Is a Key Splicing Regulator in the p53 Tumor Suppression Program.

Although TP53 is the most commonly mutated gene in human cancers, the p53-dependent transcriptional programs mediating tumor suppression remain incompletely understood. Here, to uncover critical components downstream of p53 in tumor suppression, we perform unbiased RNAi and CRISPR-Cas9-based genetic screens in vivo. These screens converge upon the p53-inducible gene Zmat3, encoding an RNA-binding protein, and we demonstrate that ZMAT3 is an important tumor suppressor downstream of p53 in mouse KrasG12D-driven lung and liver cancers and human carcinomas. Integrative analysis of the ZMAT3 RNA-binding landscape and transcriptomic profiling reveals that ZMAT3 directly modulates exon inclusion in transcripts encoding proteins of diverse functions, including the p53 inhibitors MDM4 and MDM2, splicing regulators, and components of varied cellular processes. Interestingly, these exons are enriched in NMD signals, and, accordingly, ZMAT3 broadly affects target transcript stability. Collectively, these studies reveal ZMAT3 as a novel RNA-splicing and homeostasis regulator and a key component of p53-mediated tumor suppression

Impact of early Polynesian occupation on the land snail fauna of Henderson Island, Pitcairn group (South Pacific)

Henderson Island, an uninhabited raised coral atoll in the Pitcairn group, has recently been designated a World Heritage Site because of its unique and relatively undisturbed ecosystem. The island is believed to have been uplifted and subaerially exposed during the last 275 kyr. This therefore provides the maximum age for the terrestrial biota that includes several endemic taxa. Henderson today supports 16 strictly terrestrial species of snails, about half of which are endemic. Analyses of sediments beneath Polynesian occupation horizons dated between the 11th and 17th centuries AD, have yielded 11 species of land snail present in the modern fauna, together with at least six (and possibly as many as eight) further species that no longer occur on the island. These extinct taxa are illustrated and formal descriptions provided for five (Pleuropoma hendersoni, Orobophana carinacosta, Minidonta macromphalus, Philonesia pyramidalis, P. weisleri); a sixth, known only from broken shells, appears to belong to the genus Hiona. The two remaining taxa are 'tornatellinids' that have not been recognized among the modern fauna. Radiocarbon dates from bones of associated extinct land birds confirm their occurrence on Henderson before the first signs of Polynesian settlement. The extinction of these taxa seems to coincide with the Polynesian occupation and evidence for large-scale burning, at least around parts of the plateau margin, suggests that their demise can be linked with habitat destruction. At least three species, Gastrocopta pediculus, Lamellidea oblonga and Pupisoma orcula, first appear in Polynesian occupation horizons. Their status as prehistoric introductions is therefore confirmed but G. pediculus no longer lives on Henderson. Pacificella variabilis, Tornatellides oblongus parvulus and Elasmias sp., all previously thought to have been other prehistoric introductions to Henderson, were recovered from pre-Polynesian levels and are therefore native