Synapse-specific downregulation of NMDA receptors by early experience: a critical period for plasticity of sensory input to olfactory cortex

Olfaction is required at birth for survival; however, little is known about the maturation of olfactory cortical circuits. Here we show that in vivo sensory experience mediates the development of excitatory transmission in pyramidal neurons of rat olfactory cortex. We find a postnatal critical period during which there is an experience-dependent increase in the contribution of AMPARs versus NMDARs to transmission at primary sensory synapses but not associational inputs. The shift in receptors underlying transmission is mediated by a strong activity-dependent downregulation of NMDARs and modest increase in AMPARs. Sensory activity leads to a loss of "silent" NMDAR-only synapses and an increase in threshold for inducing long-term plasticity. These results indicate the importance of early olfactory experience in the establishment of cortical circuits and could reflect mechanisms governing early olfactory "imprinting."     

Fusogenic activity of EFF-1 is regulated via dynamic localization in fusing somatic cells of C. elegans

BACKGROUND: Many animal tissues form via fusion of cells. Yet in all instances of developmental cell fusion, the mechanism underlying fusion of plasma membranes remains poorly understood. EFF-1 is required for most somatic cell fusions in C. elegans, and misexpressed EFF-1 alters the normal pattern of fusing hypodermal cells. However, the autonomous activity of EFF-1, the rules governing its specificity, and the mechanism of its action have not been examined. RESULTS: We show that EFF-1 acts as a cellular fusogen, capable of inducing fusion of virtually any somatic cells in C. elegans, yet targeted precisely to fusion-fated contacts during normal development. Misexpression of EFF-1 in early embryos causes fusion among groups of cells composed entirely of nonfusion-fated members. Measurements of cytoplasm diffusion in induced fusion events show that ectopic EFF-1 expression produces fusion pores similar to those in normal fusion events. GFP-labeled EFF-1 is specifically targeted to fusion-competent cell contacts via reciprocal localization to the touching membranes of EFF-1-expressing cells. EFF-1 function is also governed by intercellular barriers that prohibit cell fusion between distinct tissues. Analysis of mutant versions of EFF-1 indicates a novel mode of fusogenicity, employing neither a phospholipase active site nor hydrophobic fusion-peptide acting solely in pore formation. CONCLUSIONS: EFF-1 can confer potent fusogenic activity to nonfusing cell types. However, it is normally targeted only to fusion-fated cell borders via mutual interaction between EFF-1-expressing cells and relocalization to the plasma membrane. Because EFF-1 appears evolutionarily unique to nematodes, multiple mechanisms may have evolved for controlled plasma-membrane fusion in development.     

A life table for the cinnabar mothTyria jacobaeae,in Oregon

The cinnabar moth,Tyria jacobaeae L. (Arctiidae), was introduced into Oregon in 1960 against the weed tansy ragwort,Senecio jacobaea L., and in 1970 an intensive study of a population of this biological control agent was initiated. Field sampling methods were devised, and laboratory investigations of feeding and larval development were conducted. Results of the study were analyzed and reported as partial life tables, where possible mortality factors were identified and quantified. The most important mortality factor in both 1970 and 1971 was starvation after defoliation of host plants. Other factors identified included pupal death, emergence failure, egg predation, and larval ingestion of eggs.     

Regenerative potential of human muscle stem cells in chronic inflammation

Introduction

Chronic inflammation is a profound systemic modification of the cellular microenvironment which could affect survival, repair and maintenance of muscle stem cells. The aim of this study was to define the role of chronic inflammation on the regenerative potential of satellite cells in human muscle.

Methods

As a model for chronic inflammation, 11 patients suffering from rheumatoid arthritis (RA) were included together with 16 patients with osteoarthritis (OA) as controls. The mean age of both groups was 64 years, with more females in the RA group compared to the OA group. During elective knee replacement surgery, a muscle biopsy was taken from the distal musculus vastus medialis. Cell populations from four RA and eight OA patients were used for extensive phenotyping because these cell populations showed no spontaneous differentiation and myogenic purity greater than 75% after explantation.

Results

After mononuclear cell explantation, myogenic purity, viability, proliferation index, number of colonies, myogenic colonies, growth speed, maximum number of population doublings and fusion index were not different between RA and OA patients. Furthermore, the expression of proteins involved in replicative and stress-induced premature senescence and apoptosis, including p16, p21, p53, hTERT and cleaved caspase-3, was not different between RA and OA patients. Mean telomere length was shorter in the RA group compared to the OA group.

Conclusions

In the present study we found evidence that chronic inflammation in RA does not affect the in vitro regenerative potential of human satellite cells. Identification of mechanisms influencing muscle regeneration by modulation of its microenvironment may, therefore, be more appropriate.