Maternal Life Satisfaction and Child Outcomes: Are They Related?

This paper investigates the association between maternal life satisfaction and the developmental functioning of two- to three-year-old children as well as the socio-emotional behaviorof five- to six-year-old children. We use data from the German Socio-Economic Panel Study (SOEP), which allows us to control for a rich set of child and parental characteristics and to use the mother's life satisfaction before the birth of her child as an instrument to eliminate potential reverse causality. The results indicate that the more satisfied the mother, the better her child's verbal skills and the lower his or her socio-emotional problems. The relation is more pronounced for boys than for girls. The results are robust even when mothers' personality or mothers' cognitive skills are controlled for.Life satisfaction, subjective well-being, mothers, children, child development, skill formation, instrumental variable

A Role For Microtubule Dynamics For The Induction Of Chromosomal Instability And Cell Migration And Invasion In Human Cancer Cells

Aneuploidy and increased cell migration and invasion are hallmarks of aggressive human cancers. Aneuploidy derives from an increased rate of perpetual chromosome missegregation during mitosis, referred to as chromosomal instability (CIN). CIN contributes to the development of genetic heterogeneity and is thought to support rapid adaptation of cancer cells. Significantly, late tumor stages, which exhibit metastasis, are not only characterized by increased cancer cell migration and invasion, but also by high levels of CIN, both of which correlate with poor patient prognosis. Therefore, I aimed to investigate a potential link between CIN and increased cell migration and invasion in aggressive human cancer cells. In this study, I found that CIN per se is not sufficient to trigger increased cancer cell migration and invasion. However, a hyperactive TRIO-Rac1-Arp2/3 pathway acts as a shared trigger for both, the development of CIN and cancer cell migration and invasion. Hyperactivation of TRIO, Rac1 and the Arp2/3 complex depends on increased microtubule plus-end assembly rates and on the localization of the Rac1-GEF TRIO to microtubule plus-ends via the microtubule end-binding protein EB1. In mitosis, microtubule dependent hyperactivation of the pathway causes spindle positioning defects leading to erroneous microtubule-kinetochore attachments and the generation of lagging chromosomes, which constitute a common cause for chromosome missegregation and CIN. Inhibition of TRIO, Rac1 or the Arp2/3 complex suppressed these phenotypes and prevented the development of aneuploidy in chromosomally instable colon cancer cells. In interphase, the hyperactivity of TRIO, Rac1 and the Arp2/3 complex resulted in highly enhanced cancer cell migration and invasion. Analogous to the situation in mitosis, restoration of proper microtubule dynamics in interphase suppressed the migratory and invasive phenotype in invasive colorectal cancer and melanoma cells. Thus, these results demonstrate a mechanistic link between the regulation of the actin and the microtubule cytoskeleton important for the development of CIN as well as for triggering cancer cell migration and invasion. As one important trigger that can cause increase of microtubule plus-end assembly rates in both, mitosis and in interphase I identified a concomitant loss of the transcription factors p53 and p73. In fact, my studies suggest that p53 and p73 cooperate in maintaining chromosomal stability and suppressing cancer cell migration and invasion

Early changes in alpha band power and DMN BOLD activity in Alzheimer's disease: a simultaneous resting state EEG-fMRI study

Simultaneous resting state functional magnetic resonance imaging (rsfMRI)-resting state electroencephalography (rsEEG) studies in healthy adults showed robust positive associations of signal power in the alpha band with BOLD signal in the thalamus, and more heterogeneous associations in cortical default mode network (DMN) regions. Negative associations were found in occipital regions. In Alzheimer's disease (AD), rsfMRI studies revealed a disruption of the DMN, while rsEEG studies consistently reported a reduced power within the alpha band. The present study is the first to employ simultaneous rsfMRI-rsEEG in an AD sample, investigating the association of alpha band power and BOLD signal, compared to healthy controls (HC). We hypothesized to find reduced positive associations in DMN regions and reduced negative associations in occipital regions in the AD group. Simultaneous resting state fMRI-EEG was recorded in 14 patients with mild AD and 14 HC, matched for age and gender. Power within the EEG alpha band (8-12 Hz, 8-10 Hz, and 10-12 Hz) was computed from occipital electrodes and served as regressor in voxel-wise linear regression analyses, to assess the association with the BOLD signal. Compared to HC, the AD group showed significantly decreased positive associations between BOLD signal and occipital alpha band power in clusters in the superior, middle and inferior frontal cortex, inferior temporal lobe and thalamus (p < 0.01, uncorr., cluster size ≥ 50 voxels). This group effect was more pronounced in the upper alpha sub-band, compared to the lower alpha sub-band. Notably, we observed a high inter-individual heterogeneity. Negative associations were only reduced in the lower alpha range in the hippocampus, putamen and cerebellum. The present study gives first insights into the relationship of resting-state EEG and fMRI characteristics in an AD sample. The results suggest that positive associations between alpha band power and BOLD signal in numerous regions, including DMN regions, are diminished in AD

Combined Cyclosporin A and Hypothermia Treatment Inhibits Activation of BV-2 Microglia but Induces an Inflammatory Response in an Ischemia/Reperfusion Hippocampal Slice Culture Model

Introduction: Hypothermia attenuates cerebral ischemia-induced neuronal cell death associated with neuroinflammation. The calcineurin inhibitor cyclosporin A (CsA) has been shown to be neuroprotective by minimizing activation of inflammatory pathways. Therefore, we investigated whether the combination of hypothermia and treatment with CsA has neuroprotective effects in an oxygen-glucose deprivation/reperfusion (OGD/R) injury model in neuronal and BV-2 microglia monocultures, as well as in an organotypic hippocampal slice culture (OHSC). Methods: Murine primary neurons, BV-2 microglia, and OHSC were pretreated with CsA and exposed to 1 h OGD (0.2% O2) followed by reperfusion at normothermia (37°C) or hypothermia (33.5°C). Cytotoxicity was measured by lactate dehydrogenase and glutamate releases. Damage-associated molecular patterns (DAMPs) high mobility group box 1 (HMGB1), heat shock protein 70 (Hsp70), and cold-inducible RNA-binding protein (CIRBP) were detected in cultured supernatant by western blot analysis. Interleukin-6 (IL-6), Interleukin-1α and -1β (IL-1α/IL1-β), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein 1 (MCP1), inducible nitric oxide synthase (iNOS), glia activation factors ionized calcium-binding adapter molecule 1 (Iba1), and transforming growth factor β1 (TGF-β1) gene expressions were analyzed by RT-qPCR. Results: Exposure to OGD plus 10 μM CsA was sufficient to induce necrotic cell death and subsequent release of DAMPs in neurons but not BV-2 microglia. Moreover, OGD/R-induced secondary injury was also observed only in the neurons, which was not attenuated by cooling and no increased toxicity by CsA was observed. BV-2 microglia were not sensitive to OGD/R-induced injury but were susceptible to CsA-induced toxicity in a dose dependent manner, which was minimized by hypothermia. CsA attenuated IL-1β and Iba1 expressions in BV-2 microglia exposed to OGD/R. Hypothermia reduced IL-1β and iNOS expressions but induced TNF-α and Iba1 expressions in the microglia. However, these observations did not translate to the ex vivo OHCS model, as general high expressions of most cytokines investigated were observed. Conclusion: Treatment with CsA has neurotoxic effects on primary neurons exposed to OGD but could inhibit BV-2 microglia activation. However, CsA and hypothermia treatment after ischemia/reperfusion injury results in cytotoxic neuroinflammation in the complex ex vivo OHSC

Generation of 4-vinylguaiacol through a novel high-affinity ferulic acid decarboxylase to obtain smoke flavours without carcinogenic contaminants

Traditional smoke flavours bear the risk of containing a multitude of contaminating carcinogenic side-products. Enzymatic decarboxylation of ferulic acid released from agro-industrial side-streams by ferulic acid esterases (FAE) enables the sustainable generation of pure, food grade 4-vinylguaiacol (4-VG), the impact compound of smoke flavour. The first basidiomycetous ferulic acid decarboxylase (FAD) was isolated from Schizophyllum commune (ScoFAD) and heterologously produced by Komagataella phaffii. It showed a molecular mass of 21 kDa, catalytic optima at pH 5.5 and 35 C, and a sequence identity of 63.6% to its next relative, a FAD from the ascomycete Cordyceps farinosa. The ScoFAD exhibited a high affinity to its only known substrate ferulic acid (FA) of 0.16 mmol L-1 and a turnover number of 750 s-1. The resulting catalytic efficiency kcat KM-1 of 4,779 L s-1 mmol-1 exceeded the next best known enzyme by more than a factor of 50. Immobilised on AminoLink Plus Agarose, ScoFAD maintained its activity for several days. The combination with FAEs and agro-industrial side-streams paves the way for a new generation of sustainable, clean, and safe smoke flavours

Luther als Vater des Kapitalismus?

Warum ist es moralisch verwerflich, sich dem „süßen Müßiggang“ hinzugeben? Oder ist es das etwa gar nicht? Warum wird von Menschen als „Sozialschmarotzern“ gesprochen, die sich nicht dem Diktat des 8-Stunden-Arbeitstages unterwerfen wollen? Warum setzt so manchem das Gewissen zu, wenn er keiner „geregelten“ Arbeit nachgeht? Was treibt den Menschen dazu, mehr zu arbeiten, als er für seinen notwendigen Lebensunterhalt eigentlich müsste? Diese am Anfang der vorliegenden Arbeit gestellten Fragen gilt es zu beantworten. Werden „Luther“ und „Kapitalismus“ in einem Satz erwähnt, assoziieren die meisten wohl Webers „Protestantische Ethik und der Geist des Kapitalismus“ damit. Die vorliegende Arbeit nähert sich diesem Thema aus philosophischer Sicht: Max Webers aufgestellte These, der Kapitalismus sei maßgeblich ein Produkt der protestantischen Ethik, hatte einen heftigen akademischen Diskurs vor allem im Bereich der Soziologie ausgelöst. Aber haben diese beiden doch vom Prinzip her so unterschiedlichen gedanklichen Konstrukte überhaupt Gemeinsamkeiten? Lässt sich an der Entwicklung des Kapitalismus und des Protestantismus eine Parallele herauslesen? Und wenn nicht, dann muss die Frage lauten: Warum leben wir – obwohl entweder atheistisch oder nicht gläubig oder anders gläubig – in calvinistischer Tradition? In Kapitel II wird zunächst der amorphe Begriff „Kapitalismus“ definiert, um dann die Entwicklung des Kapitalismus zu skizzieren. Kapitel III stellt die protestantische Ethik anhand von Martin Luther und Johannes Calvin sowie ihrer Schüler bzw. aus ihren Lehren weiterentwickelte Traditionen dar. Kapitel IV widmet sich Webers Werk und seiner Wirkgeschichte. In Kapitel V werden die einzelnen Argumentationsstränge zusammengefasst und auf den Punkt gebracht: Die Änderung der Werte.Why should it be immoral being idle? Why are people named "cadger" who do not want to live by the rule of an 8-hour working day? Why does one feel guilty not having any "regular" work? What creates the need to work more than you would have to for a living? It is to answer those questions posed at the beginning of the present work. On mentioning "Luther" and "Capitalism" in one sentence, most would probably associate Weber's "Protestant ethic and the spirit of capitalism". The thesis approaches this topic from a philosophical perspective: Max Weber's established these, capitalism was a relevant product of the Protestant Ethics, had triggered a fierce academic discourse, especially in the area of sociology. But do these in principle so different ideas at all have anything in common? Is there a parallel in the development of Capitalism and Protestantism? And if not, the question occurrs: why do we live - although either atheistic or not a believer or otherwise faith – in Calvinist tradition? In chapter II the amorphous term "Capitalism" is defined, followed by an outline of the development of capitalism. Chapter III introduces the Protestant ethic based on Martin Luther and John Calvin, and their students or on their doctrines evolved traditions. Chapter IV is devoted to Weber's work and its active history. In chapter V are the individual strands of argument abstractet to the point: the change of values

Tea: A High-level Language and Runtime System for Automating Statistical Analysis

Though statistical analyses are centered on research questions and hypotheses, current statistical analysis tools are not. Users must first translate their hypotheses into specific statistical tests and then perform API calls with functions and parameters. To do so accurately requires that users have statistical expertise. To lower this barrier to valid, replicable statistical analysis, we introduce Tea, a high-level declarative language and runtime system. In Tea, users express their study design, any parametric assumptions, and their hypotheses. Tea compiles these high-level specifications into a constraint satisfaction problem that determines the set of valid statistical tests, and then executes them to test the hypothesis. We evaluate Tea using a suite of statistical analyses drawn from popular tutorials. We show that Tea generally matches the choices of experts while automatically switching to non-parametric tests when parametric assumptions are not met. We simulate the effect of mistakes made by non-expert users and show that Tea automatically avoids both false negatives and false positives that could be produced by the application of incorrect statistical tests.Comment: 11 page

A DyP-type peroxidase of pleurotus sapidus with alkene cleaving activity

Alkene cleavage is a possibility to generate aldehydes with olfactory properties for the fragrance and flavor industry. A dye-decolorizing peroxidase (DyP) of the basidiomycete Pleurotus sapidus (PsaPOX) cleaved the aryl alkene trans-anethole. The PsaPOX was semi-purified from the mycelium via FPLC, and the corresponding gene was identified. The amino acid sequence as well as the predicted tertiary structure showed typical characteristics of DyPs as well as a non-canonical Mn2+-oxidation site on its surface. The gene was expressed in Komagataella pfaffii GS115 yielding activities up to 142 U/L using 2,20-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) as substrate. PsaPOX exhibited optima at pH 3.5 and 40 ◦C and showed highest peroxidase activity in the presence of 100 µM H2O2 and 25 mM Mn2+. PsaPOX lacked the typical activity of DyPs towards anthraquinone dyes, but oxidized Mn2+ to Mn3+. In addition, bleaching of β-carotene and annatto was observed. Biotransformation experiments verified the alkene cleavage activity towards the aryl alkenes (E)-methyl isoeugenol, α-methylstyrene, and trans-anethole, which was increased almost twofold in the presence of Mn2+. The resultant aldehydes are olfactants used in the fragrance and flavor industry. PsaPOX is the first described DyP with alkene cleavage activity towards aryl alkenes and showed potential as biocatalyst for flavor production