Novel protein composition of a bacterial membrane.
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Bacillus↗
Biomedical subjects
P H Patterson
Publications and source records attributed to P H Patterson.
Cytokine and growth factor involvement in long-term potentiation.
Hippocampal long-term potentiation (LTP) is one of the best-studied models of learning and memory at the molecular level. While it has long been known that tetanic stimulation causes changes at the synapse within seconds to minutes, recent research has begun to focus on factors that may affect synaptic plasticity on a longer time scale. One group of factors with many of the characteristics predicted for both short- and long-term actions at the synapse is the cytokines and growth factors. In vitro, these proteins can alter neuronal morphology, gene expression, and proliferation, and many cytokines and their receptors are present in the adult CNS. Because brainderived neurotrophic factor (BDNF) is the best-studied synaptic modulator of this class, we begin by discussing the experimental evidence linking BDNF to LTP. Ten cytokines and growth factors that have been examined in the context of hippocampal LTP are then considered. We discuss the effects of LTP on the expression of the cytokines and explore the regulation of synaptic plasticity by exogenous application or antagonist perturbation of these proteins. The available evidence strongly supports a role for these factors in synaptic modulation and should prompt further exploration of their functions at the synapse.
Animals↗
Activins as candidate cholinergic differentiation factors in vivo.
A number of cytokine families have been implicated in shaping neuronal survival, growth and gene expression. The neuropoietic and transforming growth factor-beta (TGF-beta) cytokines, in particular, have emerged as candidates for regulating the phenotype of sympathetic neurons. Culture studies have shown that neuropoietic cytokines (such as leukemia inhibitory factor, ciliary neurotrophic factor, oncostatin M, growth promoting activity) can induce the cholinergic enzyme, choline acetyltransferase (ChAT) and several neuropeptides, whereas certain members of the TGF-beta family (activin A, bone morphogenetic proteins-2 and -6) induce partially overlapping but distinct sets of transmitter and neuropeptide genes in sympathetic neurons. Since activins can induce ChAT in cultured neurons, we have investigated whether these cytokines are expressed by the appropriate cells and tissues to make them candidates for the cholinergic differentiation factor that is known to alter the phenotype of sympathetic neurons that innervate the sweat gland in the footpad in vivo. In-situ hybridization with the anti-sense probe for activin beta B specifically labels the sweat glands but not other tissues in the footpads of developing rats. Ribonuclease protection assays indicate that beta B as well as the other activin and inhibin subunit mRNAs are expressed by a number of tissues, including footpad, hairy skin and submaxillary gland. Homogenates of developing rat footpads, however, failed to induce the set of neuropeptide genes in cultured sympathetic neurons that is characteristic for activins, although neuropoietic cytokine activity was readily detectable in this assay. Thus, while activin beta B mRNA is expressed in the sweat gland, this tissue does not contain detectable activin protein as assayed by its ability to regulate neuronal gene expression. Moreover, activin subunit mRNAs are expressed by targets of noradrenergic sympathetic neurons in vivo, indicating that activin expression is not limited to targets of cholinergic neurons.
Activins↗
New anti-huntingtin monoclonal antibodies: implications for huntingtin conformation and its binding proteins.
We produced eight anti-huntingtin (Htt) monoclonal antibodies (mAbs), several of which have novel binding patterns. Peptide array epitope mapping shows that mAbs MW1-6 specifically bind the polyQ domain of Htt exon 1. On Western blots of extracts from mutant Htt knock-in mouse brain and Huntington's disease lymphoblastoma cell lines, MW1-5 all strongly prefer to bind to the expanded polyQ repeat form of Htt, displaying no detectable binding to normal Htt. These results suggest that the polyQ domain can assume different conformations that are distinguishable by mAbs. This idea is supported by immunohistochemistry with wild type (WT) and mutant Htt transgenic mouse (R6) brains. Despite sharing the same epitope and binding preferences on Western blots, MW1-5 display distinct staining patterns. MW1 shows punctate cytoplasmic and neuropil staining, while MW2-5 strongly stain the neuronal Golgi complex. MW6, in contrast, stains neuronal somas and neuropil. In addition, despite their preference for mutant Htt on blots, none of these mAbs show enhanced staining of R6 brains over WT, and show no binding of the Htt-containing nuclear inclusions in R6 brains. This suggests that in its various subcellular locations, the polyQ domain of Htt either takes on different conformations and/or is differentially occluded by Htt binding proteins. In contrast to MW1-6, MW7, and 8 can differentiate transgenic from WT mice by staining nuclear inclusions in R6/2 brain; MW8 displays no detectable staining in WT brain and stains only inclusions in R6/2 brain. Epitope mapping reveals that MW7 and 8 specifically bind the polyP domains and amino acids 83-90, respectively. As with MW1-6, the epitopes for MW7 and 8 are differentially available in the various subcellular compartments where Htt is found.
Amino Acid Sequence↗
Cytokine responses to LTP induction in the rat hippocampus: a comparison of in vitro and in vivo techniques.
Because exogenous application of a number of cytokines and growth factors can alter synaptic properties, we sought to determine if endogenous cytokine expression is affected by neuronal activity. In addition, we examined whether cytokine expression is altered by the techniques used to stimulate and record from hippocampal neurons. Using semi-quantitative RNase protection and RT-PCR assays, we studied the expression of 18 cytokine, growth factor, and receptor genes in the hippocampus following the induction of Schaffer collateral-CA1 long-term potentiation (LTP). We found that various cytokines are dramatically induced following preparation of slices for in vitro recording and as a result of injury following acute electrode placement in vivo. These increases can be overcome in vivo, however, using permanent electrodes implanted three weeks prior to testing. Using this chronic preparation, we found that interleukin-6 (IL-6) mRNA was upregulated nearly 20-fold by LTP induction in vivo, marking the first demonstration of endogenous regulation of this cytokine in response to LTP. In situ hybridization for IL-6 revealed that upregulation is tightly localized near the site of stimulation and is detected only in non-neuronal cells, identified as GFAP+ astrocytes and GFAP- cells within proximal blood vessels. Coupled with previous results showing that exogenously applied IL-6 can prevent the induction of LTP, this finding suggests a mechanism by which the local release of a cytokine could regulate LTP at nearby sites.
Animals↗
Hatching eggs sanitized with chlorine dioxide foam: egg hatchability and bactericidal properties.
The efficacy of chlorine dioxide (ClO2) as an alternative sanitizing agent for hatching eggs was investigated because of the health concerns about formaldehyde fumigation. Hatchability of chicken eggs was reduced when the eggs were dipped in the ClO2 solutions for more than 5 minutes or in concentrations greater than 100 ppm Cl. However, treating hatching eggs with a ClO2 foam or fumigating with formaldehyde had no adverse effect on hatchability compared with untreated control eggs. Sanitizing soiled duck eggs with ClO2 foam improved hatchability by more than 10% and hatch by more than 6% compared with untreated eggs (P less than 0.05). A novel method for assessing bactericidal potential of egg-sanitizing agents was developed. Using this technique, both chlorine dioxide foam and formaldehyde fumigation reduced the number of egg-contaminant bacteria inoculated on sterile chicken eggs compared with the number of bacteria on untreated eggs (P less than 0.05). These findings suggest that sanitizing hatching eggs with ClO2 foam may be a viable alternative to fumigating with formaldehyde.
Animals↗