Dual activity maps in primate visual cortex produced by different temporal patterns of zif268 mRNA and protein expression

The inducible nature of the immediate-early genes (IEGs) c-fos and zif268 allows their products to be used as activity markers in the brain. The utility of such markers in general is restricted because they can resolve only neurons activated by a single stimulus. To overcome this limitation, we have developed a double-label technique that exploits the dissimilar time course of zif268 mRNA and protein induction, allowing them to be separately induced by two different stimuli and independently stained to provide a visual display of neurons that are responsive to each stimulus. Two powerful features of this new imaging technique—the possibility of staining separate populations of activated neurons and the ability to visualize them at the cellular level—should extend IEG applications in biological activity mapping.     

Fas ligand-induced murine pulmonary inflammation is reduced by a stable decoy receptor 3 analogue

Fas ligand (FasL)-induced lung inflammation has recently been suggested to play an important role in the pathogenesis of acute respiratory disease syndrome (ARDS). In order to further explore this connection, we established a FasL-induced murine model of pulmonary inflammation. Instillation of recombinant FasL (rFasL) into the lung induced neutrophil infiltration and increased pulmonary permeability, as evidenced by increased total protein in the airspace; both occur in patients with ARDS. These effects were accompanied with a rapid induction of proinflammatory mediators: cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) and the chemokines macrophage inflammatory protein-2 (MIP-2) and KC. Pretreatment with a FasL antagonist, a decoy receptor 3 analogue (DcR3 analogue), reduced neutrophil infiltration into the airspace and resulted in a highly significant reduction in the levels of GM-CSF, MIP-2 and KC in bronchoalveolar lavage (BAL) fluid. We postulate that rFasL may be responsible for induction of proinflammatory chemokines and cytokines in the lung, which in turn attract neutrophil infiltration into the airspace. This proinflammatory process and the associated pulmonary permeability may, in part, explain the association of FasL with severe pulmonary inflammation, such as ARDS, and shed new light on FasL and its role in lung injury.     

Nuclear translocation controlled by alternatively spliced isoforms inactivates the QUAKING apoptotic inducer

The quaking viable mice have myelination defects and develop a characteristic tremor 10 d after birth. The quaking gene encodes at least five alternatively spliced QUAKING (QKI) isoforms that differ in their C-terminal 8--30-amino-acid sequence. The reason for the existence of the different QKI isoforms and their function are unknown. Here we show that only one QKI isoform, QKI-7, can induce apoptosis in fibroblasts and primary rat oligodendrocytes. Heterodimerization of the QKI isoforms results in the nuclear translocation of QKI-7 and the suppression of apoptosis. The unique C-terminal 14 amino acids of QKI-7 confers the ability to induce apoptosis to heterologous proteins such as the green fluorescent protein and a QKI-related protein, Caenorhabditis elegans GLD-1. Thus, the unique C-terminal sequences of QKI-7 may function as a life-or-death 'sensor' that monitors the balance between the alternatively spliced QKI isoforms. Moreover, our findings suggest that nuclear translocation is a novel mechanism of inactivating apoptotic inducers.     

Differences in Caffeine 3-Demethylation Activity among Inbred Mouse Strains: A Comparison of Hepatic Cyp 1a2 Gene Expression between Two Inbred Strains

The 3-demethylation of caffeine can be used as an index of cytochromeP450 CYP1A2 activity in vivo. We compared the plasma levelsof caffeine and the 3-demethylated metabolite, 1,7-dimethylxanthine,in six common inbred strains (A/J, P/J, BALB/cJ, C3H/HeJ, AKR/J,and SWR/J) and one inbred strain (APN) derived in our laboratoryfrom outbred Swiss-Webster mice on the basis of its relativesusceptibility to acetaminophen-induced hepatotoxicity. We foundsignificant variations between a number of the common strains,all of which produced significantly higher caffeine 3-demethylationindices than our APN strain. In three of the six common strains,there was a significant difference between males and females,with the females having consistently lower 1,7-xanthine/caffeineratios. Hepatic Cyp1a2 expression was compared between APN andC3H/HeJ males. Microsomal methoxyresorufin O-demethylation,acetanilide 4-hydroxylation, and CYP1A2 immunoreactive proteinlevels were significantly higher in C3H/HeJ relative to APNmice, as were hepatic CYP1A2 mRNA levels. These results indicatethe importance of strain and gender to the outcome of pharmacologicalor toxicological studies involving CYP1A2-mediated metabolism,as well as the suitability of the plasma 1,7-dimethylxanthine/caffeineratio as a marker of CYP1A2 activity in the mouse. The strikingdifferences observed between the APN and C3H/HeJ mice suggestthat these strains may be suitable for a genetic analysis ofthe regulation of the basal expression of CYP1A2, a key enzymeIn procarcinogen activation.     

Mental health assessment: Inference,explanation, and coherence

Mental health professionals such as psychiatrists and psychotherapists assess their patients by identifying disorders that explain their symptoms. This assessment requires an inference to the best explanation that compares different disorders with respect to how well they explain the available evidence. Such comparisons are captured by the theory of explanatory coherence that states 7 principles for evaluating competing hypotheses in the light of evidence. The computational model ECHO shows how explanatory coherence can be efficiently computed. We show the applicability of explanatory coherence to mental health assessment by modelling a case of psychiatric interviewing and a case of psychotherapeutic evaluation. We argue that this approach is more plausible than Bayesian inference and hermeneutic interpretation.     

Family-centered care in Ontario general hospitals: the views of pediatric nurses

Registered nurses and registered practical nurses working on pediatric units in 35 Ontario general hospitals participated in a study that examined their perceptions and practices of family-centered care (FCC). The Family-Centered Care Questionnaire-Revised (FCCQ-R) was used to collect the data. The participants were asked to rate their level of agreement regarding necessary elements (perceptions) of family-centered care and whether these elements are part of their current work (practice). The participants had a reasonable knowledge of the necessary elements of family-centered care, but were not consistently including these in their every day work. A number of barriers to the implementation of family-centered care were also identified. Perception and practice scores were higher among those who had participated in continuing education on family-centered care than those who had not. The findings suggest that some nurses may be having difficulties shifting from a medical helping model of care to an enabling helping model of care, which is considered the foundation of family-centered care. Difficulties in implementing family-centered care appear to be systemic, both at the unit and organizational level. Based on the findings, implications for practice, education and research are suggested.