Ceramide selectively decreases tau levels in differentiated PC12 cells through modulation of calpain I

Ceramide has been recently proposed to be a signal mediator in several important physiological processes including apoptosis, cellular growth, and differentiation. Because the microtubule-associated protein tau plays an important role in the establishment and maintenance of neuronal morphology, the effects of ceramide on tau were examined. Treatment of differentiated PC12 cells with the cell-permeable ceramide derivative N-acetylsphingosine (C2) resulted in a significant reduction in tau levels. Significant decreases in tau levels were also observed when the cells were treated with another ceramide derivative, N-hexanoylsphingosine (C6). In addition, C2 treatment increased the levels of a calpain-derived spectrin breakdown product but did not alter the levels of two cytoskeletal proteins, alpha-actin and alpha-tubulin. Because both tau and spectrin are proteolyzed in vitro by the calcium-activated cysteine protease calpain, the effects of ceramide analogues on the activity of this protease were examined. Treatment of PC12 cells with C2 enhanced calcium-stimulated proteolytic activity significantly, as revealed by monitoring the hydrolysis of the membrane-permeable calpain-selective fluorescence probe N-succinyl-L-leucyl-L-leucyl-L-valyl-L-tyrosine-7-amido-4-methylcoumarin . This activity increase was not due to a direct effect of C2 on calpains, because C2 did not alter the activities of purified calpain I or II. In addition, C2 treatment of PC12 cells resulted in a significant increase in the levels of calpain I and, to a lesser extent, the levels of calpastatin (an endogenous calpain inhibitor protein), whereas the levels of calpain II were not changed. Moreover, treatment of the cells with the synthetic calpain-specific inhibitor N-carbobenzoxy-L-leucyl-L-leucyl-L-tyrosine diazomethyl ketone blocked the C2-induced decreases in tau levels. These results indicate that tau levels are regulated in response to a physiological factor and, thus, have implications for ceramide-mediated changes in normal and pathological neuronal processes.     

Concentrations and emission rates of aerial ammonia, nitrous oxide, methane, carbon dioxide, dust and endotoxin in UK broiler and layer houses

Standard treatment for limited stage adenocarcinoma of the breast includes lumpectomy (or a quadrantectomy), axillary node dissection, regional radiation therapy and, if the prognostic factors are unfavourable, chemotherapy and/or hormone therapy. This is supported by the results of American and European randomised trials. There have been many attempts at improving the modalities of conservative surgery and postoperative radiation therapy in order to maximize local control and minimize late sequellae. It is also likely that induction chemotherapy and external beam radiotherapy applied in selected cases increase the proportion of patients who can be offered conservative surgery.     

Evidence for a third component in neutrophil aggregation: potential roles of O-linked glycoproteins as L-selectin counter-structures

The homotypic aggregation of neutrophils requires the participation of L-selectin and the beta 2-integrins, but it has not been clear whether the two receptors recognize one another as counter-structures or whether other adhesion molecules are involved. We have examined aggregation of live neutrophils with target populations, manipulated to alter expression of adhesive epitopes, using flow cytometry. A target population depleted of both L-selectin and activatable beta 2-integrin displayed an ability to aggregate with live neutrophils, suggesting that these two molecules are not counter-structures. We also found that an O-sialoglycoprotease (GCP) from Pasteurella haemolytica is capable of inhibiting homotypic aggregation. Neutrophils treated with GCP lose O-glycosylated proteins but retain L-selectin and activatable beta 2-integrin. One or more of the GCP substrates appears to function in L-selectin-dependent binding but not in beta 2-integrin-dependent binding. Together the data suggest a mechanism of aggregation that is analogous to leukocyte-endothelial cell adhesion in which a low-affinity carbohydrate-dependent interaction precedes a high-affinity integrin-dependent adhesion.     

Acoustic startle and prepulse inhibition in 40 inbred strains of mice.

A high-throughput phenotype screening protocol was used to measure the acoustic startle response (ASR) and prepulse inhibition (PPI) in mice. ASRs were evoked by noise bursts; prepulses for PPI were 70 dB sound pressure level tones of 4, 12, and 20 kHz. Forty inbred strains of mice were tested (in most cases using 10 males and 10 females of each strain). The data on both the ASR and PPI had high internal and test-retest reliability and showed large differences among inbred strains, indicative of strong genetic influences. Previously obtained measures of hearing sensitivity in the same inbred strains were not significantly correlated with ASR or PPI measures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nature, extent, and impact of Superfund hazardous waste sites

Uncontrolled hazardous waste sites are major environmental and public health concerns in the United States and elsewhere. The identification and remediation of and public health responses to these sites are mandated by the U.S. federal Superfund statute. Since its enactment into law in 1980, approximately 40,000 uncontrolled waste sites have been identified in the United States. Approximately 1,300 of these sites constitute the current national Superfund priority list of sites for remediation. Results from analyses are described that characterize the priority hazardous substances released from Superfund sites and the extent of hazard posed to residential communities. Findings from the United States' experience in responding to uncontrolled waste sites are relevant to other countries as they address similar environmental and public health concerns.     

Nicotinic and muscarinic cholinergic receptor binding in the human hippocampal formation during development and aging

High-affinity nicotine, alpha-bungarotoxin (alpha BT) and muscarinic receptor binding was measured in the human hippocampal formation in a series of 57 cases aged between 24 weeks gestation and 100 years. Changes in nicotine receptor binding during development and aging were more striking than differences in alpha BT and muscarinic binding. Nicotine binding was higher at the late foetal stage than at any other subsequent time in all areas investigated. In the hippocampus a fall in binding then occurred within the first six months of life, with little or no subsequent fall during aging, whereas in the entorhinal cortex and the presubiculum the major loss of nicotine binding occurred after the fourth decade. alpha BT binding was significantly elevated in the CA 1 region, but in no other region of the hippocampus, in the late foetus, and there was also a fall in alpha BT binding in the entorhinal cortex during aging from the second decade. The modest changes in total muscarinic binding, which appeared to reflect those in M1 and M3 + 4 rather than M2 binding, were a rise in the entorhinal cortex between the foetal stage and childhood and a tendency for receptors to fall with age in the hippocampus and subicular complex. These findings implicate mechanisms controlling the expression of nicotinic receptors to a greater extent than muscarinic receptors in postnatal development and aging in the human hippocampus.