Functional analysis of the fibrinogen-related scabrous gene from Drosophila melanogaster identifies potential effector and stimulatory protein domains

The scabrous (sca) gene encodes a secreted dimeric glycoprotein with putative coiled-coil domains N-terminally and a C-terminal region related to the blood clot protein fibrinogen. Homozygous sca mutants have extra bristle organs and rough eyes. We describe a GAL4-based expression system for testing rescue of the sca mutant phenotype by altered SCA proteins and for misexpression. We find that deletion of the fibrinogen-related domain (FReD) greatly decreases SCA function, confirming the importance of this conserved region. SCA function could not be restored by FReDs from human fibrinogen chain genes. However, proteins lacking any FReD still showed some function in both rescue and misexpression experiments, suggesting that putative effector-binding regions lie outside this domain. Consistent with this, proteins expressing only the FReD had no rescuing activity but were recessive negative; i.e., they enhanced the phenotype of sca mutations but had no phenotype in the presence of a wild-type sca allele. This suggests that the FReD contributes to SCA function by binding to other components of the bristle determination pathway, increasing the activity of the linked N-terminal region.     

In vitro system for differentiating pluripotent neural crest cells into smooth muscle cells

The change in vascular smooth muscle cells (SMC) from a differentiated to a dedifferentiated state is the critical phenotypic response that promotes occlusive arteriosclerotic disease. Despite its importance, research into molecular mechanisms regulating smooth muscle differentiation has been hindered by the lack of an in vitro cell differentiation system. We identified culture conditions that promote efficient differentiation of Monc-1 pluripotent neural crest cells into SMC. Exclusive Monc-1 to SMC differentiation was indicated by cellular morphology and time-dependent induction of the SMC markers smooth muscle alpha-actin, smooth muscle myosin heavy chain, calponin, SM22alpha, and APEG-1. The activity of the SM22alpha promoter was low in Monc-1 cells. Differentiation of these cells into SMC caused a 20-30-fold increase in the activity of the wild-type SM22alpha promoter and that of a hybrid promoter containing three copies of the CArG element. By gel mobility shift analysis, we identified new DNA-protein complexes in nuclear extracts prepared from differentiated Monc-1 cells. One of the new complexes contained serum response factor. This Monc-1 to SMC model should facilitate the identification of nodal regulators of smooth muscle development and differentiation.     

Confidence-accuracy inversions in scene recognition: a remember-know analysis

S. E. Clark (1997) offered a modified signal-detection explanation of the confidence-accuracy inversions observed in E. Tulving's (1981) experiments. In addition to replicating E. Tulving (1981), we had participants make "remember-familiar" judgments. Confidence and accuracy dissociated across subjective reports. Response confidence differed only for judgments based on familiarity, whereas accuracy differed only for "remember" responses. S. E. Clark's model does not predict this, nor can it mimic "remember" performance across all conditions. We propose that although "knowing" can be accommodated within an equal variance signal-detection account, "remembering" is governed by contextual constraints that influence the distinctiveness of information upon which participants rely during reports. The current paradigm is a pictorial analogue to H. L. Roediger and K. B. McDermott's paradigm (1995) in that participants claim to explicitly remember thematically related items that were not actually seen during study.     

Social support and hostility as predictors of depressive symptoms in cardiac patients one month after hospitalization: a prospective study

OBJECTIVE: Hospitalization for cardiac disease is associated with an increased risk for depression, which itself confers a poorer prognosis. Few prospective studies have examined the determinants of depression after hospitalization in cardiac patients, and even fewer have examined depression within the weeks after hospital discharge. The present study assessed the prospective relations among perceptions of social support and trait hostility in predicting symptoms of depressive symptoms at 1 month after hospitalization for a diagnostic angiography in 506 coronary artery disease (CAD) patients. METHOD: A series of structural equation models 1) estimated the predictive relations of social support, hostility, and depressive symptoms while in the hospital to symptoms of depression 1 month after hospitalization, and 2) compared these relations across gender, predicted risk classification, and age. RESULTS: Social support assessed during hospitalization was independently negatively associated with depressive symptoms 1 month after hospitalization, after controlling for baseline symptoms of depression, gender, disease severity, and age. Hostility was an indirect predictor of postdischarge depressive symptomology by way of its negative relation with social support. This pattern of relations did not differ across gender, predicted risk classification, and age. CONCLUSIONS: Our findings suggest that a patient's perceived social support during hospitalization is a determinant of depressive symptoms 1 month later. The relation of social support and hostility to subsequent depressive symptoms was similar across a variety of populations.     

Development of penicillin resistance among Staphylococcus aureus isolated from bovine mastitis in Denmark and other countries

A short-term, problem-focused Individual Psychological Support (IPS) intervention was evaluated. The IPS was one of the interventions in a study where 527 patients newly diagnosed with breast, colorectal, gastric or prostate cancer were randomised between IPS (n = 265) and a control condition (n = 262). The IPS made use of cognitive-behavioural techniques and aimed at reducing depression and anxiety, to increase the feeling of mastery of the situation and to facilitate active participation in medical treatments. Half of the patients receiving the IPS had more than 2 sessions. After termination of the IPS, the patients were mailed a questionnaire concerning satisfaction with and perceived benefit from the IPS. A majority of the responding patients stated that their problems were addressed to a great extent, that the number of contacts was adequate and that the IPS came at the right time. Patients reporting problems received more sessions and perceived more benefits than patients reporting no problems.     

Engineering analysis of biological variables: an example of blood pressure over 1 day

Almost all variables in biology are nonstationarily stochastic. For these variables, the conventional tools leave us a feeling that some valuable information is thrown away and that a complex phenomenon is presented imprecisely. Here, we apply recent advances initially made in the study of ocean waves to study the blood pressure waves in the lung. We note first that, in a long wave train, the handling of the local mean is of predominant importance. It is shown that a signal can be described by a sum of a series of intrinsic mode functions, each of which has zero local mean at all times. The process of deriving this series is called the "empirical mode decomposition method." Conventionally, Fourier analysis represents the data by sine and cosine functions, but no instantaneous frequency can be defined. In the new way, the data are represented by intrinsic mode functions, to which Hilbert transform can be used. Titchmarsh [Titchmarsh, E. C. (1948) Introduction to the Theory of Fourier Integrals (Oxford Univ. Press, Oxford)] has shown that a signal and i times its Hilbert transform together define a complex variable. From that complex variable, the instantaneous frequency, instantaneous amplitude, Hilbert spectrum, and marginal Hilbert spectrum have been defined. In addition, the Gumbel extreme-value statistics are applied. We present all of these features of the blood pressure records here for the reader to see how they look. In the future, we have to learn how these features change with disease or interventions.     

Functioning of the hypophyseal-adrenocortical system in rats selected for the sensitivity threshold to the electric current

Although behavioral and neuropsychological data regarding the existence of images for odors are inconclusive, reconsideration of earlier EEG work provides reasonably clear evidence for an inner nose. However, further EEG studies and neuroimaging data seem essential for conclusive demonstration of an inner nose.     

Crystal structure of cytoplasmic Escherichia coli peptidyl-prolyl isomerase: evidence for decreased mobility of loops upon complexation

Ryanodine receptors (RyRs), a class of intracellular calcium release channels, are the largest ion channels known. Recently, cryoelectron microscopy and image reconstructions of isolated receptors have shown that most of the protein mass forms a porous, multidomain cytoplasmic assembly. Evidence is mounting that suggests that the cytoplasmic assembly communicates with the transmembrane regions over distances of 100 or greater. RyRs are centrally important in excitation-contraction coupling, which occurs at specialized regions where the sarcoplasmic reticulum, containing the RyRs, and the plasma membrane/transverse-tubule system form junctions. Numerous proteins are present at these junctions, some of which interact directly with the RyR.     

Effects of meta-chlorophenylpiperazine infusions in patients with seasonal affective disorder and healthy control subjects. Diurnal responses and nocturnal regulatory mechanisms

BACKGROUND: Multiple lines of evidence suggest that brain serotonergic systems may be disturbed in seasonal affective disorder (SAD). Previously, we found that the serotonergic agent meta-chlorophenylpiperazine (m-CPP) produced increases in activation and euphoria in depressed patients with SAD, but not in patients with SAD following light treatment or in the summer, nor in healthy control subjects in any condition. In the present study, we attempted to replicate and extend this finding using better methods. METHODS: Seventeen outpatients with SAD and 15 control subjects underwent successive 3-week periods of bright light treatment and light avoidance in a randomized order. During the third week of each condition, on 2 different occasions, subjects were admitted to the hospital for a night of sleep (core temperatures were recorded), followed by infusions of m-CPP (0.08 mg/kg) or placebo the next morning. Dependent measures included the 24-item National Institute of Mental Health Self-Rating Scale, plasma corticotropin, cortisol, prolactin, growth hormone, and norepinephrine concentrations, and core temperatures. RESULTS: Meta-chlorophenylpiperazine produced (1) significant increases in "activation-euphoria" ratings only in depressed patients with SAD in the untreated condition and (2) blunted corticotropin and norepinephrine responses in patients with SAD compared with controls across both light treatment conditions. In both groups, light treatment was associated with significant reductions in nocturnal core temperatures, which were correlated with similarly significant reductions in mean diurnal growth hormone concentrations. In patients with SAD, (1) the reductions in nocturnal core temperatures also were correlated with the reductions in baseline depression ratings and (2) the reductions in mean growth hormone concentrations were significantly smaller compared with controls. CONCLUSIONS: The abnormal m-CPP-induced activation-euphoria responses represent a replicated state marker of winter depression in patients with SAD. The blunted m-CPP-induced responsiveness of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system may represent traitlike abnormalities. The improvements in mood following light treatment in patients with SAD seem to be associated with the lowering of nocturnal core temperatures. The findings, although not easily explained based on a uniform abnormality of serotonin receptors, are nonetheless compatible with the notion that selected regions of the central nervous system are deficient in serotonin transmission during winter depression.