Interleukin-1 induces rapid and transient expression of the c-fos proto-oncogene in isolated pancreatic islets and in purified β-cells

AbstractThe effect of interleukin-1β (IL-1) on expression of c-fos mRNA in isolated rat pancreatic islets was examined. Accumulation of c-fos mRNA was demonstrable after 30 min of exposure to IL-1, peaked by 60 min, and declined thereafter. Fluorescence-activated cell sorting (FACS) of dispersed islet cells was employed to localize the accumulation of c-fos mRNA to the β-cell. Cycloheximide did not influence the induction of c-fos mRNA by IL-1. Accumulation of c-fos mRNA therefore appears to be an early signal transduction event in the β-cell and a component of the cellular mechanism(s) by which IL-1 influences β-cell function

Ontology, natural language, and information systems: Implications of cross-linguistic studies of geographic terms

Ontology has been proposed as a solution to the 'Tower of Babel' problem that threatens the semantic interoperability of information systems constructed independently for the same domain. In information systems research and applications, ontologies are often implemented by formalizing the meanings of words from natural languages. However, words in different natural languages sometimes subdivide the same domain of reality in terms of different conceptual categories. If the words and their associated concepts in two natural languages, or even in two terminological traditions within the same language, do not have common referents in the real world, an ontology based on word meanings will inherit the 'Tower of Babel' problem from the languages involved, rather than solve it. In this paper we present evidence from a preliminary comparison of landscape terms in English with those in the Yindjibarndi language of northwestern Australia demonstrating that this problem is not just hypothetical. Some possible solutions are suggested

Manganese-coated IRIS to document reducing soil conditions

Iron-coated indicatorof reduction in soils (IRIS) devices have been used for nearly two decades to help assess and document reducing conditions in soils, and official guidance has been approved for interpreting these data. Interest in manganese (Mn)-coated IRIS devices has increased because Mn oxides are reduced under more moderately reducing conditions than iron (Fe) oxides (which require strongly reducing conditions), such that they are expected to be better proxies for some important ecosystem services like denitrification. However, only recently has the necessary technology become available to produce Mn-coated IRIS, and the need is now emerging for guidance in interpreting data derived from Mn IRIS. Ninety-six data sets collected over a 2-yr period from 40 plots at 18 study sites among eight states were used to compare the performance of Mn-coated IRIS with Fe-coated IRIS and to assess the effect of duration of saturation and soil temperature as environmental drivers on the reduction and removal of the oxide coating. It appears that the current threshold prescribed by the National Technical Committee for Hydric Soils for Fe-coated IRIS is appropriate for periods when soil temperatures are warmer (\u3e11 °C), but is unnecessarily conservative when soil temperatures are cooler (5–11 °C). In contrast, Mn-coated devices are particularly useful early in the growing season when soil temperatures are cool. Our data show that when using a threshold of 30% removal of Mn oxide coatings there is essentially 100% confidence of the presence of reducing soil conditions under cool (\u3c11 °C) conditions

A microtiter virus yield reduction assay for the evaluation of antiviral compounds against human cytomegalovirus and herpes simplex virus

Although the virus yield reduction assay is a powerful technique for evaluating the efficacy of antiviral compounds, it is not routinely utilized due to its labor-intensive nature. This procedure was modified, developed, thereby reducing greatly the time and effort required to perform yield reduction assays. Monolayer cultures of mammalian cells were grown in 96-well microtiter tissue culture plates and infected with virus. Test compounds were added and serially diluted directly with the plates. Following a cycle of virus replication, culture lysates were made and serially diluted in a separate set of uninfected cultures grown in microtiter plates. The cultures were incubated, plaques were enumerated in wells containing 5 to 20 plaques, and virus titers were calculated. To illustrate the use of the assay the known antiviral drugs acyclovir and ganciclovir were evaluated using this procedure. Ninety percent inhibitory concentrations for the respective drugs were 3 [mu]M and 0.7 [mu]M against herpes simplex virus type 1 and 60 [mu]M and 1 [mu]M against human cytomegalovirus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28636/1/0000450.pd

Nanobodies Raised against Monomeric α-Synuclein Distinguish between Fibrils at Different Maturation Stages

AbstractNanobodies are single-domain fragments of camelid antibodies that are emerging as versatile tools in biotechnology. We describe here the interactions of a specific nanobody, NbSyn87, with the monomeric and fibrillar forms of α-synuclein (αSyn), a 140-residue protein whose aggregation is associated with Parkinson's disease. We have characterized these interactions using a range of biophysical techniques, including nuclear magnetic resonance and circular dichroism spectroscopy, isothermal titration calorimetry and quartz crystal microbalance measurements. In addition, we have compared the results with those that we have reported previously for a different nanobody, NbSyn2, also raised against monomeric αSyn. This comparison indicates that NbSyn87 and NbSyn2 bind with nanomolar affinity to distinctive epitopes within the C-terminal domain of soluble αSyn, comprising approximately amino acids 118–131 and 137–140, respectively. The calorimetric and quartz crystal microbalance data indicate that the epitopes of both nanobodies are still accessible when αSyn converts into its fibrillar structure. The apparent affinities and other thermodynamic parameters defining the binding between the nanobody and the fibrils, however, vary significantly with the length of time that the process of fibril formation has been allowed to progress and with the conditions under which formation occurs, indicating that the environment of the C-terminal domain of αSyn changes as fibril assembly takes place. These results demonstrate that nanobodies are able to target forms of potentially pathogenic aggregates that differ from each other in relatively minor details of their structure, such as those associated with fibril maturation