HONO emissions from soil bacteria as a major source of atmospheric reactive nitrogen.

Abiotic release of nitrous acid (HONO) in equilibrium with soil nitrite (NO2(-)) was suggested as an important contributor to the missing source of atmospheric HONO and hydroxyl radicals (OH). The role of total soil-derived HONO in the biogeochemical and atmospheric nitrogen cycles, however, has remained unknown. In laboratory experiments, we found that for nonacidic soils from arid and arable areas, reactive nitrogen emitted as HONO is comparable with emissions of nitric oxide (NO). We show that ammonia-oxidizing bacteria can directly release HONO in quantities larger than expected from the acid-base and Henry's law equilibria of the aqueous phase in soil. This component of the nitrogen cycle constitutes an additional loss term for fixed nitrogen in soils and a source for reactive nitrogen in the atmosphere.

Phospholipid metabolism regulated by a transcription factor sensing phosphatidic acid.

Cells regulate the biophysical properties of their membranes by coordinated synthesis of different classes of lipids. Here, we identified a highly dynamic feedback mechanism by which the budding yeast Saccharomyces cerevisiae can regulate phospholipid biosynthesis. Phosphatidic acid on the endoplasmic reticulum directly bound to the soluble transcriptional repressor Opi1p to maintain it as inactive outside the nucleus. After the addition of the lipid precursor inositol, this phosphatidic acid was rapidly consumed, releasing Opi1p from the endoplasmic reticulum and allowing its nuclear translocation and repression of target genes. Thus, phosphatidic acid appears to be both an essential ubiquitous metabolic intermediate and a signaling lipid.

Phospholipase D1 and potential targets of its hydrolysis product, phosphatidic acid.

Phospholipase D (PLD) hydrolyses phosphatidylcholine into phosphatidic acid (PA) and choline. Our work aims to understand the properties of PLD1, and to identify downstream targets of PA. In one set of projects, we have focused on membrane-targeting mechanisms and have proposed a hierarchy of signals that allows PLD1 to localize to intracellular membranes. These signals involve a functional pleckstrin homology (PH) domain and its fatty acylation on two adjacent cysteine residues. A nearby Phox homology (PX) domain may modulate the function of the fatty acylated PH domain. This complex array of signals is probably necessitated by the targeting of PLD1 to multiple endocytic and secretory membranes under basal and signal-dependent conditions. In another set of projects, we have used chemically synthesized PA coupled to a solid support in order to identify proteins that interact with this phospholipid. Several proteins have emerged from this screen as potential targets. Some (e.g. ADP-ribosylation factor, coatomer beta subunit) are involved in trafficking and their PA affinity can be understood in terms of their regulated cycling on and off membranes during rounds of transport. Others (sphingosine 1-phosphate kinase and PtdIns4 P 5-kinase) are implicated in pathways that also involve PLD activation. Others still are novel proteins (brain-specific neurochondrin) whose affinity for PA may contribute to an understanding of their cellular function.

Functional MRI of the human brain: predominance of signals from extracerebral veins.

This study demonstrates the predominance of extracerebral vascular signals in gradient-echo functional magnetic resonance imaging of motor activity at 1.5 Tesla. The demonstration is based upon a novel experimental approach. Maximum intensity projection images are derived from a large set of contiguous 2D functional MR images, and compared with MR angiograms obtained from the volume covered by the set of functional MR images. The comparison shows that the hyperintensities in the functional MR images cover extensive areas, which can be superimposed with a number of veins in the MR angiograms. These results should trigger a general caution in interpretation of the observations in 1.5 Tesla functional MRI.