Investigating the biology of consciousness.

The fact that consciousness is a private, first-person phenomenon makes it more difficult to study than other cognitive phenomena that, although being equally private, also have characteristic behavioural signatures. Nonetheless, by combining cognitive and neurobiological methods, it is possible to approach consciousness, to describe its cognitive nature, its behavioural correlates, its possible evolutionary origin and functional role; last but not least, it is possible to investigate its neuroanatomical and neurophysiological underpinnings. In this brief essay I distinguish between two kinds of consciousness: core consciousness and extended consciousness. Core consciousness corresponds to the transient process that is incessantly generated relative to any object with which an organism interacts, and during which a transient core self and transient sense of knowing are automatically generated. Core consciousness requires neither language nor working memory, and needs only a brief short-term memory. Extended consciousness is a more complex process. It depends on the gradual build-up of an autobiographical self, a set of conceptual memories pertaining to both past and anticipated experiences of an individual, and it requires conventional memory. Extended consciousness is enhanced by language.     

N-acetyl-sphingenine-1-phosphate is a potent calcium mobilizing agent.

Calcium mobilization induced by phosphorylated sphingoid bases was analyzed in calf pulmonary artery endothelial cells by confocal microscopy. A sphingenine-1-phosphate (SeP) analogue, N-acetyl-sphingenine-1-phosphate (N-C2-SeP), exogenously added to these cells, caused a fast and transient intracellular rise in calcium and was as potent as SeP. A minimal concentration of 0.6 nM for N-C2-SeP versus 1 nM for SeP was determined. The N-C2-SeP-induced Ca2+-signaling, like the response to SeP, was due to a release from thapsigargin-sensitive, ryanodine-insensitive, intracellular Ca2+-stores and not to a Ca2+-influx. N-C2-SeP can be considered as a truncated ceramide-phosphate, a lipid already reported to be mitogenic (Gomez-Munoz, A., Duffy, P.A., Martin, A., O'Brien, L., Byun, H.S., Bittman, R. and Brindley, D.N. (1995) Mol. Pharmacol. 47, 833-839), an effect that might be secondary to Ca2+-mobilization.     

Detailed flow patterns in the nasal cavity.

The human nasal cavity filters and conditions inspired air while providing olfactory function. Detailed experimental study of nasal airflow patterns has been limited because of the complex geometry of the nasal cavity. In this work, particle image velocimetry was used to determine two-dimensional instantaneous velocity vector fields in parallel planes throughout a model of the nasal cavity that was subjected to a nonoscillatory flow rate of 125 ml/s. The model, which was fabricated from 26 computed tomography scans by using rapid prototyping techniques, is a scaled replica of a human right nasal cavity. The resulting vector plots show that the flow is laminar and regions of highest velocity are in the nasal valve and in the inferior airway. The relatively low flow in the olfactory region appears to protect the olfactory bulb from particulate pollutants. Low flows were also observed in the nasal meatuses, whose primary function has been the subject of debate. Comparison of sequentially recorded data suggests a steady flow.     

A novel glycosphingolipid from gram-negative aquatic bacteria.

The chloroform-methanol extractable lipids of the Gram-negative fresh-water bacteria Arcocella aquatica NO-502 and Flectobacillus major FM were found to contain an unusual ninhydrin-positive glycolipid. It was purified by two-stage silica gel-column chromatography. By the use of IR and (1)H-NMR spectroscopy, mass spectrometry and chemical-degradation experiment, the lipid was established to be 1-O-monoglycosyl ceramide, the carbohydrate moiety of which was the alpha-pyranose-ring form of 7-desoxy-7-amino-D-manno-heptulosonic acid, or 1-hydroxycarbonyl-6-deoxy-6-amino-alpha-D-mannopyranose. The ceramide portion consisted mainly (by 95% in the A. aquatica glycolipid and 80% in the F. major glycolipid) of 2-N-(2'-D-hydroxy-13'-methyltetradecanoyl)-15-methyl-4(E)-hexad ecasph ingenine. The minor molecular species differed from the major one only in fatty acid structure. The glycolipid accounted for 8 and 11% of the total lipids extracted from A. aquatica NO-502 and F. major FM cells, respectively.     

Inhibition of GSK-3β Rescues the Impairments in Bone Formation and Mechanical Properties Associated with Fracture Healing in Osteoblast Selective Connexin 43 Deficient Mice

Connexin 43 (Cx43) is the most abundant gap junction protein in bone and is required for osteoblastic differentiation and bone homeostasis. During fracture healing, Cx43 is abundantly expressed in osteoblasts and osteocytes, while Cx43 deficiency impairs bone formation and healing. In the present study we selectively deleted Cx43 in the osteoblastic lineage from immature osteoblasts through osteocytes and tested the hypothesis that Cx43 deficiency results in delayed osteoblastic differentiation and impaired restoration of biomechanical properties due to attenuated β-catenin expression relative to wild type littermates. Here we show that Cx43 deficiency results in alterations in the mineralization and remodeling phases of healing. In Cx43 deficient fractures the mineralization phase is marked by delayed expression of osteogenic genes. Additionally, the decrease in the RankL/ Opg ratio, osteoclast number and osteoclast size suggest decreased osteoclast bone resorption and remodeling. These changes in healing result in functional deficits as shown by a decrease in ultimate torque at failure. Consistent with these impairments in healing, β-catenin expression is attenuated in Cx43 deficient fractures at 14 and 21 days, while Sclerostin (Sost) expression, a negative regulator of bone formation is increased in Cx43cKO fractures at 21 days, as is GSK-3β, a key component of the β-catenin proteasomal degradation complex. Furthermore, we show that alterations in healing in Cx43 deficient fractures can be rescued by inhibiting GSK-3β activity using Lithium Chloride (LiCl). Treatment of Cx43 deficient mice with LiCl restores both normal bone formation and mechanical properties relative to LiCl treated WT fractures. This study suggests that Cx43 is a potential therapeutic target to enhance fracture healing and identifies a previously unknown role for Cx43 in regulating β-catenin expression and thus bone formation during fracture repair.