Loss of the Putative Catalytic Domain of HDAC4 Leads to Reduced Thermal Nociception and Seizures while Allowing Normal Bone Development

Histone deacetylase 4 (HDAC4) has been associated with muscle & bone development [1]–[6]. N-terminal MEF2 and RUNX2 binding domains of HDAC4 have been shown to mediate these effects in vitro. A complete gene knockout has been reported to result in premature ossification and associated defects resulting in postnatal lethality [6]. We report a viral insertion mutation that deletes the putative deacetylase domain, while preserving the N-terminal portion of the protein. Western blot and immuno-precipitation analysis confirm expression of truncated HDAC4 containing N-terminal amino acids 1-747. These mutant mice are viable, living to at least one year of age with no gross defects in muscle or bone. At 2–4 months of age no behavioral or physiological abnormalities were detected except for an increased latency to respond to a thermal nociceptive stimulus. As the mutant mice aged past 5 months, convulsions appeared, often elicited by handling. Our findings confirm the sufficiency of the N-terminal domain for muscle and bone development, while revealing other roles of HDAC4

Laser biospectroscopy and 5-ALA fluorescence navigation as a helpful tool in the meningioma resection

5-aminolevulinic acid (5-ALA) is a natural precursor of protoporphyrin IX (PP IX), which possesses fluorescent properties and is more intensively accumulated in tumor cells than in normal tissue. Therefore, the use of 5-ALA in the surgical treatment of intracranial tumors, particularly gliomas, has gained popularity in the last years, whereas its use in other intracranial pathological entities including meningiomas has been reported occasionally. This study describes a series of 28 patients with intracranial meningiomas, who were administered 5-ALA for a better visualization of tumor boundaries. Twelve patients underwent also laser spectroscopic analysis in order to confirm the visual impression of tumor tissue visualization. Bone infiltration was readily demonstrated. In one case, the tumor recurrence could have been prevented by removal of a tumor remnant, which would possibly have been better recognized if spectroscopic analysis had been used. Fluorescent navigation (FN) is a useful method for maximizing the radicality of meningioma surgery, particularly if the tumor infiltrates the bone, the skull base, and/or the surrounding structures

Carbon Fluxes Across Boundaries in the Pacific Arctic Region in a Changing Environment

While the inflow of dissolved inorganic carbon (DIC) from the Pacific Ocean is relatively well quantified, the intermittent input from the East Siberian Sea (ESS) is not. The export flux to the Atlantic Ocean has unknown uncertainty due to a paucity of DIC data from the Canadian Archipelago. Within the region, the Chukchi Sea is the dominant site for atmospheric carbon dioxide (CO2) uptake, while the Beaufort Sea and the Canadian Archipelago take-up much less CO2 with latter potentially a weak source of CO2 during certain times of the year. Additionally, the ESS shelf is a net source of CO2. Summertime CO2 uptake capacity in the deep Canada Basin has increased greatly recently as sea-ice retreat progresses rapidly. The region appears to export more DIC than it receives by a small amount, suggesting that it is probably weakly net heterotrophic. In addition to labile organic carbon (OC) produced in the productive marginal seas, some riverine and coastal erosion-derived OC likely is also recycled. As warming progresses, the Arctic Ocean may produce and export more DIC. Whether this change will turn the Arctic Ocean into a weaker CO2 sink or even a CO2 source for the atmosphere is uncertain and dependent on multiple factors that control the rate of surface water CO2 increase versus the rate of the atmospheric CO2 increase