A sensitive bioassay for chicken interleukin-18 based on the inducible release of preformed interferon-gamma

Conventional tests for measuring the biological activity of chicken interleukin (IL)-18 require primary chicken spleen cells. We now describe a sensitive bioassay that is based on interleukin-18-induced release of interferon (IFN)-gamma by a permanent chicken cell line. In B19-2D8 cells, cytoplasmically stored interferon-gamma is quickly secreted in response to interleukin-18 exposure.     

The Arabidopsis PILZ group genes encode tubulin-folding cofactor orthologs required for cell division but not cell growth

Plant microtubules are organized into specific cell cycle-dependent arrays that have been implicated in diverse cellular processes, including cell division and organized cell expansion. Mutations in four Arabidopsis genes collectively called the PILZ group result in lethal embryos that consist of one or a few grossly enlarged cells. The mutant embryos lack microtubules but not actin filaments. Whereas the cytokinesis-specific syntaxin KNOLLE is not localized properly, trafficking of the putative auxin efflux carrier PIN1 to the plasma membrane is normal. The four PILZ group genes were isolated by map-based cloning and are shown to encode orthologs of mammalian tubulin-folding cofactors (TFCs) C, D, and E, and associated small G-protein Arl2 that mediate the formation of alpha/beta-tubulin heterodimers in vitro. The TFC C ortholog, PORCINO, was detected in cytosolic protein complexes and did not colocalize with microtubules. Another gene with a related, although weaker, embryo-lethal phenotype, KIESEL, was shown to encode a TFC A ortholog. Our genetic ablation of microtubules shows their requirement in cell division and vesicle trafficking during cytokinesis, whereas cell growth is mediated by microtubule-independent vesicle trafficking to the plasma membrane during interphase.     

The Topography of Non-Linear Cortical Dynamics at Rest, in Mental Calculation and Moving Shape Perception

Differential cortical activation by cognitive processing was studied using dimensional complexity, a measure derived from nonlinear dynamics that indicates the degrees of freedom (complexity) of a dynamic system. We examined the EEG of 32 healthy subjects at rest, during a visually presented calculation task, and during a moving shape perception task. As a nonlinear measure of connectivity, the mutual dimension of selected electrode pairs was used. The first Lyapunov coefficient was also calculated. Data were tested for non-linearity using a surrogate data method and compared to spectral EEG measures (power, coherence). Surrogate data testing confirmed the presence of nonlinear structure in the data. Cognitive activation led to a highly significant rise in dimensional complexity. While both tasks activated central, parietal and temporal areas, mental arithmetic showed frontal activation and an activity maximum at T3, while the moving shape task led to occipital activation and a right parietal activity maximum. Analysis of mutual dimension showed activation of a bilateral temporal-right frontal network in calculation. The Lyapunov coefficent showed clear topographic variation, but was not significantly changed by mental tasks (p<.09). While dimensional complexity was almost unrelated to power values, nonlinear (mutual dimension) and linear (coherence) measures of connectivity shared up to 37% of variance. Data are interpreted in terms of increased cortical complexity as a result of recruitment of asynchronously active, distributed neuronal assemblies in cognition. The topography of nonlinear dynamics are related to neuropsychological and neuroimaging findings on mental calculation and moving shape perception.     

Genomic gain of PIK3CA and increased expression of p110alpha are associated with progression of dysplasia into invasive squamous cell carcinoma

The regulation of apoptosis in atherosclerosis is not completely defined. The aim of this study was to determine the expression of Bcl-2, Bcl-x, Bax, and Bak in relation to apoptosis in advanced atherosclerotic lesions. In atherectomy (15), endarterectomy (10), and control non-atherosclerotic segments of renal (2) and of coronary and carotid (5) arteries, the extent of apoptosis was determined using TdT dUTP nick end labelling (TUNEL) and nuclear morphology (karyorrhexis/pyknosis) and expression of apoptosis regulators by immunohistochemistry and western blot analysis on paraffin-embedded material. In all specimens, the atherosclerotic involvement was advanced: grade V (n=18) and grade VI (n=7). The apoptotic index was high (mean 30%) in advanced lesions compared with controls (<2%) and smooth muscle cells (SMCs) were the predominant cell type undergoing apoptosis. In all TUNEL-positive apoptotic cells, Bax and Bak were present, while Bcl-x was absent. Bcl-2 was absent in a majority of these cells, but occasional TUNEL-positive cells expressed Bcl-2. In non-apoptotic cells, Bcl-x was present and western blot detected only the long isoform, Bcl-xL, from the plaques. In conclusion, increased Bax and Bak coupled with lack/paucity of Bcl-2 and Bcl-xL are associated with SMC apoptosis in advanced lesions. Bcl-xL in non-apoptotic cells appears to contribute to prolonged cell survival.     

Is MED13L-related intellectual disability a recognizable syndrome?

Introduction

MED13L-related intellectual disability is characterized by moderate intellectual disability (ID), speech impairment, and dysmorphic facial features. We present 8 patients with MED13L-related intellectual disability and review the literature for phenotypical and genetic aspects of previously described patients.

A systemic perspective on children’s emotional insecurity in relation to father: links to parenting,interparental conflict and children’s social well-being

ABSTRACT

Focusing on the father-child-relationship in a family systems perspective, this paper investigates longitudinal links of parenting, interparental conflict, and positive regard by both parents, to their emotional insecurity with father and mother. Furthermore, to clarify fathers’ contribution to children’s social development, aspects of the relationship to both parents are jointly considered. The sample was drawn from the German family panel pairfam and included 372 family triads with parents’ and children’s self-reports. Findings revealed consistent associations between interparental conflict and lack of positive regard and emotional insecurity, while parenting had no independent links with children’s emotional insecurity or social adjustment. Controlling for the stability of child outcomes, interparental conflict predicted children’s lower prosocial behavior and higher peer rejection. In addition, peer rejection was predicted by children’s emotional insecurity with father. The findings are in line with the emotional security hypothesis and highlight the importance of the father-child-relationship for developing positive peer relationships.     

Facilitation at the frog neuromuscular junction during and after repetitive stimulation

Summary 1. E.p.p.s and min.e.p.p.s were recorded intracellularly from Mg-blocked nerve muscle preparations (M. sartorius and M. cutaneous pectoris) of summer and winter frogs in vitro.2. Prolonged repetitive stimulation at frequencies above 5/sec induced synaptic facilitation (measured as e.p.p. increase) which continued to increase throughout the longest periods of stimulation tested (40 sec at 20/sec). For a given number of stimuli the facilitation was the greater the higher the frequency of stimulation.3. Increasing the release of ACh per impulse by reducing the Mg-concentration of the bathing solution caused a levelling off and even a depression of the e.p.p.s in the course of tetanic stimulation, i.e. the pattern of the e.p.p. response shifted towards that found in curarized preparations.4. After stimulation the e.p.p.s remained enlarged for periods from 100 to several hundreds of msec, depending on the number and frequency of the conditioning volleys. At frequencies below 100/sec the frequency of stimulation significantly influenced the amount and duration of the e.p.p. facilitation whereas at frequencies above 100/sec the duration of the e.p.p. facilitation was mainly determined by the number of conditioning volleys.5. After stimulation the frequency of the spontaneous min.e.p.p.s was increased. This increase decayed to the control level with a time course similar to that of the e.p.p. facilitation. The possibility is discussed that these parallel changes of e.p.p. amplitude and min.e.p.p. frequency are probably due to a mobilization of transmitter from its presynaptic stores to the release sites.

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Zusammenfassung 1. An Mg-blockierten Nerv-Muskel-Präparaten in vitro (M. sartorius und M. cutaneous pectoris) von Sommer- und Winterfröschen wurden intracellulär e.p.p. und min.e.p.p. gemessen.2. Lange tetanische Reizung mit Frequenzen von mehr als 5 Hz verursacht synaptische Bahnung (gemessen als e.p.p.-Vergrößerung). Diese Bahnung nimmt auch am Ende des längsten untersuchten Tetanus (40 sec bei 20 Hz) noch zu. Für eine gegebene Zahl von Reizen steigt die Bahnung mit der Reizfrequenz.3. Bei Vergrößerung der pro Impuls freigesetzten Menge ACh durch eine Reduktion der Mg-Konzentration der Badelösung erreicht die e.p.p. Amplitude im Verlauf des Tetanus ein Plateau oder beginnt sogar abzunehmen, d.h. die e.p.p. verhalten sich mehr wie in curarisierten Präparaten.4. Nach Reizung bleibt das e.p.p. gebahnt. Je nach Anzahl und Frequenz der Reize dauert die Bahnung hundert bis einige hundert Millisekunden an. Bei Reizfrequenzen von weniger als 100 Hz beeinflußt die Frequenz sowohl die Dauer als auch das Ausmaß der Potenzierung beträchtlich, während bei Frequenzen von mehr als 100 Hz die Dauer hauptsächlich durch die Zahl der Reize bestimmt wird.5. Nach Reizung ist die Frequenz der spontanen min.e.p.p. erhöht. Mit einem Zeitverlauf ähnlich dem der e.p.p.-Potenzierung kehrt die Frequenz der min.e.p.p. wieder zum Ausgangswert zurück. Diese parallelen Veränderungen der e.p.p. Amplitude und der min.e.p.p. Häufigkeit sind wahrscheinlich durch eine vermehrte Bereitstellung (Mobilisation) von Überträgersubstanz am synaptischen Spalt aus den präsynaptischen Speichern verursacht.

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With 6 Figures in the Text

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This work was supported by the Deutsche Forschungsgemeinschaft.     

Sex differences in emotional and psychophysiological responses to musical stimuli.

Although it is known that men and women differ in their music preferences and emotional reactions to music, little is known about sex differences in physiological reactions to music. In our study, we therefore set out to examine the differential reactivity to two musical stimuli that elicit distinct psychological and physiological reaction patterns. Fifty-three healthy subjects (mean age: 26.13, SD: 3.97; 26 males, 27 females) were examined. Heart rate, electrodermal activity, skin temperature, salivary cortisol, salivary alpha-amylase, and psychological variables were assessed during the course of the whole study. Following baseline assessment, two musical stimuli, which were carefully selected and rated in a pre-study as relaxing and pleasant (renaissance music) and arousing and unpleasant (heavy metal), respectively, were introduced. They were presented on two different days in a randomized order. Whereas psychological variables did not differ between men and women, results of electrophysiological measures indicate significantly different reactivity patterns between men and women. Women displayed elevated response curves to the arousing and unpleasant stimulus, whereas men did not. However, no differences were found with regards to endocrine measures in saliva. Our results demonstrate sex differences in reactivity patterns to musical stimuli in psychophysiological measures. In our study, we were able to show that women tend to show hypersensitivity to aversive musical stimuli. This finding is in accordance with previous literature on sex differences in emotion research. Furthermore, our study indicates that the confounding effects of sex differences have to be considered when using musical stimuli for emotion induction.     

Genetic polymorphisms and cerebrospinal fluid levels of tissue inhibitor of metalloproteinases 1 in sporadic Alzheimer's disease

Tissue inhibitor of metalloproteinases 1 (TIMP-1) inhibits several proteinases including a disintegrin and metalloproteinase 10 (ADAM10), a major alpha-secretase that cleaves the beta-amyloid precursor protein within its amyloidogenic Abeta domain. The gene encoding TIMP-1 (TIMP 1) maps to the short arm of the X chromosome, in a region previously suggested as conferring genetic susceptibility for Alzheimer's disease (AD). To determine whether genetic variability of TIMP 1 contributes to the pathogenesis of AD, we analysed one single nucleotide polymorphism within TIMP 1 and one single nucleotide polymorphism in the 5'-untranslated region of TIMP 1 in patients with AD and control subjects from two independent and ethnically different populations. We did not observe any association between TIMP 1 genotypes and the diagnosis of AD in men or women. We also measured TIMP-1 protein levels in the cerebrospinal fluid of patients with AD, healthy control subjects, and patients with other neurological disorders. TIMP-1 levels were similar in all groups. In addition, no significant differences were observed after stratification for TIMP 1 genotypes. Our data show that neither genetic variability nor protein levels of TIMP-1 are associated with AD.