126 research outputs found

    Identification of Melatonin-Regulated Genes in the Ovine Pituitary Pars Tuberalis, a Target Site for Seasonal Hormone Control

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    The pars tuberalis (PT) of the pituitary gland expresses a high density of melatonin (MEL) receptors and is believed to regulate seasonal physiology by decoding changes in nocturnal melatonin secretion. Circadian clock genes are known to be expressed in the PT in response to the decline (Per1) and onset (Cry1) of MEL secretion, but to date little is known of other molecular changes in this key MEL target site. To identify transcriptional pathways that may be involved in the diurnal and photoperiod-transduction mechanism, we performed a whole genome transcriptome analysis using PT RNA isolated from sheep culled at three time points over the 24-h cycle under either long or short photoperiods. Our results reveal 153 transcripts where expression differs between photoperiods at the light-dark transition and 54 transcripts where expression level was more globally altered by photoperiod (all time points combined). Cry1 induction at night was associated with up-regulation of genes coding for NeuroD1 (neurogenic differentiation factor 1), Pbef / Nampt (nicotinamide phosphoribosyltransferase) , Hif1α (hypoxia-inducible factor-1α), and Kcnq5 (K channel) and down-regulation of Rorβ, a key clock gene regulator. Using in situ hybridization, we confirmed day-night differences in expression for Pbef / Nampt, NeuroD1, and Rorβ in the PT. Treatment of sheep with MEL increased PT expression for Cry1, Pbef / Nampt, NeuroD1, and Hif1α, but not Kcnq5. Our data thus reveal a cluster of Cry1-associated genes that are acutely responsive to MEL and novel transcriptional pathways involved in MEL action in the PT

    Biopiracy <i>versus </i>one-world medicine – from colonial relicts to global collaborative concepts

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    Background: Practices of biopiracy to use genetic resources and indigenous knowledge by Western companies without benefit-sharing of those, who generated the traditional knowledge, can be understood as form of neocolonialism.Hypothesis: : The One-World Medicine concept attempts to merge the best of traditional medicine from developing countries and conventional Western medicine for the sake of patients around the globe.Study design: Based on literature searches in several databases, a concept paper has been written. Legislative initiatives of the United Nations culminated in the Nagoya protocol aim to protect traditional knowledge and regulate benefit-sharing with indigenous communities. The European community adopted the Nagoya protocol, and the corresponding regulations will be implemented into national legislation among the member states. Despite pleasing progress, infrastructural problems of the health care systems in developing countries still remain. Current approaches to secure primary health care offer only fragmentary solutions at best. Conventional medicine from industrialized countries cannot be afforded by the impoverished population in the Third World. Confronted with exploding costs, even health systems in Western countries are endangered to burst. Complementary and alternative medicine (CAM) is popular among the general public in industrialized countries, although the efficacy is not sufficiently proven according to the standards of evidence-based medicine. CAM is often available without prescription as over-the-counter products with non-calculated risks concerning erroneous self-medication and safety/toxicity issues. The concept of integrative medicine attempts to combine holistic CAM approaches with evidence-based principles of conventional medicine.Conclusion: To realize the concept of One-World Medicine, a number of standards have to be set to assure safety, efficacy and applicability of traditional medicine, e.g. sustainable production and quality control of herbal products, performance of placebo-controlled, double-blind, randomized clinical trials, phytovigilance, as well as education of health professionals and patients

    F-Actin-Dependent Regulation of NESH Dynamics in Rat Hippocampal Neurons

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    Synaptic plasticity is an important feature of neurons essential for learning and memory. Postsynaptic organization and composition are dynamically remodeled in response to diverse synaptic inputs during synaptic plasticity. During this process, the dynamics and localization of postsynaptic proteins are also precisely regulated. NESH/Abi-3 is a member of the Abl interactor (Abi) protein family. Overexpression of NESH is associated with reduced cell motility and tumor metastasis. Strong evidence of a close relationship between NESH and the actin cytoskeleton has been documented. Although earlier studies have shown that NESH is prominently expressed in the brain, its function and characteristics are yet to be established. Data from the present investigation suggest that synaptic localization of NESH in hippocampal neurons is regulated in an F-actin-dependent manner. The dynamic fraction of NESH in the dendritic spine was analyzed using FRAP (fluorescence recovery after photobleaching). Interestingly, F-actin stabilization and disruption significantly affected the mobile fraction of NESH, possibly through altered interactions of NESH with the F-actin. In addition, NESH was synaptically targeted from the dendritic shaft to spine after induction of chemical LTP (long-term potentiation) and the translocation was dependent on F-actin. Our data collectively support the significance of the F-actin cytoskeleton in synaptic targeting of NESH as well as its dynamics

    A unifying hypothesis for control of body weight and reproduction in seasonally breeding mammals

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    YesAnimals have evolved diverse seasonal variations in physiology and reproduction to accommodate yearly changes in environmental and climatic conditions. These changes in physiology are initiated by changes in photoperiod (daylength) and are mediated through melatonin, which relays photoperiodic information to the pars tuberalis of the pituitary gland. Melatonin drives thyroid‐stimulating hormone transcription and synthesis in the pars tuberalis, which, in turn, regulates thyroid hormone and retinoic acid synthesis in the tanycytes lining the third ventricle of the hypothalamus. Seasonal variation in central thyroid hormone signalling is conserved among photoperiodic animals. Despite this, different species adopt divergent phenotypes to cope with the same seasonal changes. A common response amongst different species is increased hypothalamic cell proliferation/neurogenesis in short photoperiod. That cell proliferation/neurogenesis may be important for seasonal timing is based on (i) the neurogenic potential of tanycytes; (ii) the fact that they are the locus of striking seasonal morphological changes; and (iii) the similarities to mechanisms involved in de novo neurogenesis of energy balance neurones. We propose that a decrease in hypothalamic thyroid hormone and retinoic acid signalling initiates localised neurodegeneration and apoptosis, which leads to a reduction in appetite and body weight. Neurodegeneration induces compensatory cell proliferation from the neurogenic niche in tanycytes and new cells are born under short photoperiod. Because these cells have the potential to differentiate into a number of different neuronal phenotypes, this could provide a mechanistic basis to explain the seasonal regulation of energy balance, as well as reproduction. This cycle can be achieved without changes in thyroid hormone/retinoic acid and explains recent data obtained from seasonal animals held in natural conditions. However, thyroid/retinoic acid signalling is required to synchronise the cycles of apoptosis, proliferation and differentiation. Thus, hypothalamic neurogenesis provides a framework to explain diverse photoperiodic responses.MRC. Grant Number: MR/P012205/1 - Scottish Government - BBSRC. Grant Number: BB/K001043/1 - Physiological Societ

    SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism

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    Genetic mutations of SHANK3 have been reported in patients with intellectual disability, autism spectrum disorder (ASD) and schizophrenia. At the synapse, Shank3/ProSAP2 is a scaffolding protein that connects glutamate receptors to the actin cytoskeleton via a chain of intermediary elements. Although genetic studies have repeatedly confirmed the association of SHANK3 mutations with susceptibility to psychiatric disorders, very little is known about the neuronal consequences of these mutations. Here, we report the functional effects of two de novo mutations (STOP and Q321R) and two inherited variations (R12C and R300C) identified in patients with ASD. We show that Shank3 is located at the tip of actin filaments and enhances its polymerization. Shank3 also participates in growth cone motility in developing neurons. The truncating mutation (STOP) strongly affects the development and morphology of dendritic spines, reduces synaptic transmission in mature neurons and also inhibits the effect of Shank3 on growth cone motility. The de novo mutation in the ankyrin domain (Q321R) modifies the roles of Shank3 in spine induction and morphology, and actin accumulation in spines and affects growth cone motility. Finally, the two inherited mutations (R12C and R300C) have intermediate effects on spine density and synaptic transmission. Therefore, although inherited by healthy parents, the functional effects of these mutations strongly suggest that they could represent risk factors for ASD. Altogether, these data provide new insights into the synaptic alterations caused by SHANK3 mutations in humans and provide a robust cellular readout for the development of knowledge-based therapies

    Neuropeptidomics of the Supraoptic Rat Nucleus

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    The mammalian supraoptic nucleus (SON) is a neuroendocrine center in the brain regulating a variety of physiological functions. Within the SON, peptidergic magnocellular neurons that project to the neurohypophysis (posterior pituitary) are involved in controlling osmotic balance, lactation, and parturition, partly through secretion of signaling peptides such as oxytocin and vasopressin into the blood. An improved understanding of SON activity and function requires identification and characteriza-tion of the peptides used by the SON. Here, small-volume sample preparation approaches are optimized for neuropeptidomic studies of isolated SON samples ranging from entire nuclei down to single magnocellular neurons. Unlike most previous mammalian peptidome studies, tissues are not im-mediately heated or microwaved. SON samples are obtained from ex vivo brain slice preparations via tissue punch and the samples processed through sequential steps of peptide extraction. Analyses of the samples via liquid chromatography mass spectrometry and tandem mass spectrometry result in the identification of 85 peptides, including 20 unique peptides from known prohormones. As the sample size is further reduced, the depth of peptide coverage decreases; however, even from individually isolated magnocellular neuroendocrine cells, vasopressin and several other peptides are detected

    Intestinal strongyloidiasis and hyperinfection syndrome

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    In spite of recent advances with experiments on animal models, strongyloidiasis, an infection caused by the nematode parasite Strongyloides stercoralis, has still been an elusive disease. Though endemic in some developing countries, strongyloidiasis still poses a threat to the developed world. Due to the peculiar but characteristic features of autoinfection, hyperinfection syndrome involving only pulmonary and gastrointestinal systems, and disseminated infection with involvement of other organs, strongyloidiasis needs special attention by the physician, especially one serving patients in areas endemic for strongyloidiasis. Strongyloidiasis can occur without any symptoms, or as a potentially fatal hyperinfection or disseminated infection. Th(2 )cell-mediated immunity, humoral immunity and mucosal immunity have been shown to have protective effects against this parasitic infection especially in animal models. Any factors that suppress these mechanisms (such as intercurrent immune suppression or glucocorticoid therapy) could potentially trigger hyperinfection or disseminated infection which could be fatal. Even with the recent advances in laboratory tests, strongyloidiasis is still difficult to diagnose. But once diagnosed, the disease can be treated effectively with antihelminthic drugs like Ivermectin. This review article summarizes a case of strongyloidiasis and various aspects of strongyloidiasis, with emphasis on epidemiology, life cycle of Strongyloides stercoralis, clinical manifestations of the disease, corticosteroids and strongyloidiasis, diagnostic aspects of the disease, various host defense pathways against strongyloidiasis, and available treatment options

    Organic pollutants in sea-surface microlayer and aerosol in thecoastal environment of Leghorn—(Tyrrhenian Sea)

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    The levels of dissolved and particle-associated n-alkanes, alkylbenzenes, phthalates, PAHs, anionic surfactants and surfactant fluorescent organic matter ŽSFOM. were measured in sea-surface microlayer ŽSML. and sub-surface water ŽSSL. samples collected in the Leghorn marine environment in September and October 1999. Nine stations, located in the Leghorn harbour and at increasing distances from the Port, were sampled three times on the same day. At all the stations, SML concentrations of the selected organic compounds were significantly higher than SSL values and the enrichment factors ŽEFsSML concentrationrSSL concentration. were greater in the particulate phase than in the dissolved phase. SML concentrations varied greatly among the sampling sites, the highest levels Žn-alkanes 3674 mgrl, phthalates 177 mgrl, total PAHs 226 mgrl. being found in the particulate phase in the Leghorn harbour. To improve the knowledge on pollutant exchanges between sea-surface waters and atmosphere, the validity of spray drop adsorption model ŽSDAM. was verified for SFOM, surface-active agents, such as phthalates, and compounds which can interact with SFOM, such as n-alkanes and PAHs. q2001 Elsevier Science B.V. All rights reserved

    Riskfactors and underlying mechanisms

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    Inhaltsverzeichnis Kapitel 1 Theoretischer Hintergrund 11 Einleitung 11 Interpersonelle Viktimisierung 14 Folgen interpersoneller Viktimisierung 15 Allgemeine physiologische und psychische Folgen 15 Reviktimisierung 17 Posttraumatische Belastungsstörung 20 Schuld und Scham 21 Ziele und Forschungsfragen 23 Kapitel 2 Studie I: Reviktimisierung: Ein bio-psycho- soziales Vulnerabilitätsmodell 25 Zusammenfassung 26 Abstract 26 Einleitung 27 Methodisches Vorgehen 31 Ergebnisse 32 Mit Reviktimisierung assoziierte Faktoren 32 Theorien zu Reviktimisierung 42 Ableitung eines integrativen bio- psycho-sozialen Modells der Reviktimisierung 45 Diskussion 48 Limitierungen und Forschungsausblick 48 Fazit für die Praxis 50 Kapitel 3 Studie II: Sexuelle Reviktimisierung – Bindungsbezogene Angst als zugrundeliegender Mechanismus? 51 Einleitung 52 Reviktimisierung 52 Bindung 53 Ergebnisse und Diskussion 55 Zusammenhang zwischen bindungsbezogener Angst und Reviktimisierung 55 Bindung – stabil oder veränderbar? 56 Fazit 57 Kapitel 4 Studie III: Risk Recognition, Attachment Anxiety, Self-Efficacy, and State Dissociation Predict Revictimization 59 Abstract 60 Introduction 61 Variables associated with victimization and revictimization 61 Study aim and hypotheses 64 Materials and Methods 66 Ethics statement 66 Sample and recruitment 66 Measures 67 Procedure 71 Data Analysis 71 Results 73 Baseline group differences 73 Logistic Regression Analysis Predicting Revictimization 74 Discussion 76 Kapitel 5 Studie IV: Generalized Guilt and Shame differentiate between interpersonally traumatized Women with and without Posttraumatic Stress Disorder 81 Abstract 82 Introduction 83 Methods 85 Participants 85 Procedure 85 Measures 86 Data Analysis 87 Results 88 Discussion 90 Kapitel 6 Übergeordnete Diskussion 93 Risikofaktoren für Reviktimisierung 94 Empirische Überprüfung der Risikofaktoren für Reviktimisierung 96 Schuld und Scham im Zusammenhang mit PTBS 100 Stärken und Limitierungen 102 Klinische Implikationen 104 Kapitel 7 Zusammenfassung 109 Literaturverzeichnis 113 Abbildungsverzeichnis 135 Tabellenverzeichnis 135 Summary 137 Selbstständigkeitserklärung 139 Publikationen 141Interpersonelle Traumatisierungen in der Kindheit erhöhen in der Folge das Risiko für Revik-timisierungen sowie das Risiko für verschiedene psychische Störungen wie z. B. der Post-traumatischen Belastungsstörung (PTBS). In der bisherigen Literatur werden verschiedene Variablen und Mechanismen, die Reviktimisierungstendenzen bedingen, diskutiert. Aller-dings ist die zugrundeliegende empirische Datenlage knapp und inkonsistent. Schuld und Scham in der Folge traumatischer Ereignisse gelten als Risikofaktoren für die Entstehung von PTBS und als Faktoren, die zur Aufrechterhaltung von PTBS beitragen. Während trau-maspezifische Schuld und Scham im Zusammenhang mit PTBS gut belegt sind, fehlen Stu-dien zum Zusammenhang von Trauma, PTBS und generalisierter Schuld und Scham. Ziel der Arbeit war es zunächst, Variablen, die zu Reviktimisierung beitragen können, theore-tisch zu identifizieren und Modelle zugrundeliegender Mechanismen von Reviktimisierung zu bilden (Studien I und II). Darauffolgend sollte empirisch untersucht werden, welche der theo- retisch eruierten Faktoren spezifisch mit Reviktimisierungstendenzen bei Frauen mit inter-personellen Gewalterfahrungen assoziiert sind (Studie III). Ein übergeordnetes Ziel war es, hierbei klinisch-praktische Überlegungen zur Prävention von Reviktimisierungen bei interper-sonell traumatisierter Frauen abzuleiten. Ein weiteres Ziel war es, den Forschungsstand zu PTBS und generalisierter Schuld und Scham zu erweitern, um auch hier eine Grundlage für die Optimierung von Interventionen zu schaffen (Studie IV). Es wurde ein hierarchisch geordnetes bio-psycho-soziales Modell der Reviktimisierung ent- wickelt, das Reviktimisierung als Folge multifaktorieller Prozesse darstellt. In einer zweiten theoretischen Studie wurde bindungsbezogene Angst als zugrundeliegender Mechanismus von Reviktimisierung betrachtet und als wesentlicher Risikofaktor für Reviktimisierung ver-standen. Die empirische Überprüfung der potentiellen Risikofaktoren Risikoerkennung, Selbstbehauptung, Selbstwirksamkeitsüberzeugungen, Schuld und Scham, Sensation See-king, bindungsbezogene Angst und State-Dissoziation wurde in Studie III an 34 reviktimisier-ten, 22 viktimisierten und 29 nicht-viktimisierten Probandinnen durchgeführt. In Studie IV wurden 28 traumatisierte Probandinnen mit PTBS, 32 traumatisierte Probandinnen ohne PTBS und 32 nicht-traumatisierte Probandinnen hinsichtlich expliziter und impliziter Schuld und Scham untersucht. In Studie III zeigten sich die Variablen Risikoerkennung, bindungsbezogene Angst, State Dissoziation und Selbstwirksamkeit als signifikante Prädiktoren für die Gruppenzugehörig-keit. Die Variablen bindungsbezogene Angst und Risikoerkennung konnten die viktimisierten Probandinnen von den reviktimisierten Probandinnen differenzieren. Die Ergebnisse zeigen höhere bindungsbezogene Angst und niedrigere Risikoerkennung bei den reviktimisierten verglichen mit den viktimisierten Probandinnen. Weiterhin zeigte sich, dass reviktimisierte Probandinnen kein Defizit in der Risikoerkennung aufweisen, sondern, dass die Risikoerken-nung der viktimisierten Probandinnen verglichen mit beiden anderen Gruppen erhöht war. Die Variablen State Dissoziation und Selbstwirksamkeit konnten die reviktimisierten von den nicht-viktimisierten Probandinnen differenzieren. Hierbei zeigten die reviktimisierten Proban- dinnen höhere State-Dissoziation und geringere Selbstwirksamkeit als die nicht-viktimisierten Probandinnen. Die Ergebnisse der Studie IV weisen darauf hin, dass explizite Schuld und Scham bei Frau-en mit PTBS signifikant höher war als bei traumatisierten Frauen ohne PTBS. Verglichen mit der nicht- traumatisierten Kontrollgruppe, war sowohl PTBS als auch Traumatisierung ohne PTBS mit generalisierter expliziter Schuld und Scham assoziiert. Während Traumatisierung generell (mit und ohne PTBS) mit einem impliziten zu Scham neigenden Selbstkonzept as-soziiert war, zeigte sich PTBS spezifisch mit einem impliziten zu Schuld neigenden Selbst-konzept assoziiert. Stärken der Studie III sind die sorgfältige Definition von Viktimisierung und Reviktimi-sierung, die Untersuchung von Reviktimisierung an einer schwer belasteten Stichprobe und die Differenzierung zwischen viktimisierten und reviktimisierten Probandinnen. Stärken der Studie IV ist die erstmals implizite Messung von Schuld und Scham im Zusammenhang mit Trauma und PTBS. Kritisch anzumerken ist das querschnittliche Design beider empirischer Studien, das keine Aussagen über die Richtung der gefundenen Zusammenhänge zulässt. Insgesamt legen die Befunde nahe, dass eine nicht-erhöhte Risikoerkennung bei interperso-nell traumatisierten Personen in Kombination mit den Risikofaktoren erhöhte bindungsbezo-gener Angst und erhöhte State-Dissoziation sowie verminderter Selbstwirksamkeit das Re-viktimisierungsrisiko erhöhen kann. Diese Risikofaktoren sollten in der therapeutischen Ar-beit mit interpersonell traumatisierten Personen zur Prävention von Reviktimisierung berück-sichtigt werden. Eine erhöhte Risikoerkennung bei viktimisierten Personen könnte im Sinne eines Protektionsfaktors gegenüber Reviktimisierung interpretiert werden. Schließlich weisen die Ergebnisse darauf hin, dass nicht nur traumaspezifische Schuld und Scham, sondern zusätzlich generalisierte Schuld und Scham sowie insbesondere ein stark mit Schuld assoziiertes Selbstkonzept wichtig für das Verständnis von PTBS sind und in der Planung von Interventionen bedacht werden sollten.Childhood interpersonal traumatizations increase the risk for revictimizations as well as for psychological disorders like the posttraumatic stress disorder (PTSD). Different variables and mechanisms underlying revictimization are discussed in current literature. However, empiri-cal data on revictimization is poor and inconsistant. Guilt and shame following traumatic events are considered as risk factors for the development and persistence of PTSD. PTSD is frequently associated with trauma-related guilt and shame. However, research on general-ized guilt and shame in PTSD is lacking. Aim of the dissertation was to theoretically identify variables contributing to revictimization and to develop models of underlying mechanisms of revictimization (studies I and II). Subse-quently it was aimed to empirically investigate which of these variables are specifically asso-ciated with revictimization in interpersonally victimized women (study III). A superordinate aim was to derive clinical considerations for the prevention of revictimization. Another aim was to expand the current state of research on PTSD and generalized guilt and shame to optimize interventions in this field (study IV). A hierarchical bio-psycho-social model of revictimization was developed. It presents revictim-ization as result of multifactorial processes. In a second theoretical study attachment anxiety as underlying mechanism for revictimization is investigated and considered as crucial risk factor for revictimization. The potential risk factors risk recognition, assertiveness, self-efficacy, guilt, shame, sensation seeking, attachment anxiety, and state- dissociation were investigated in study III with 34 revictimized, 22 victimized, and 29 non-victimzed individuals. In the second empirical study (study IV) 28 traumatized individuals with PTSD, 32 trauma-tized individuals without PTSD, and 32 non-traumatized individuals were investigated regard-ing explicit and implicit generalized guilt and shame. Study III showed the variables risk recognition, attachment anxiety, state-dissociation, and self- efficacy as significant predictors for group membership. Attachment anxiety and risk recognition differentiated revictimized from victimized individuals. The results show higher attachment anxiety and lower risk recognition in revictimized compared to victimized individ-uals. Furthermore, results show that revictimized individuals do not show a deficit regarding risk recognition but risk recognition in victimized individuals is increased compared to both other groups. State-dissociation and self-efficacy differentiated revictimized from non-victimized individuals. Revictimized individuals showed higher state- dissociation and lower self-efficacy than the non-victimized individuals. The results of study IV indicate that explicit guilt- and shame was significantly higher in wom-en with PTSD than in traumatized women without PTSD. However, PTSD as well as trauma-tization without PTSD are associated with generalized explicit guilt and shame. Traumatiza-tion in general (with and without PTSD) was associated with a shame-prone implicit self-concept. PTSD was specifically associated with a guilt-prone implicit self-concept. Strength of study III are the accurate definition of victimization and revictimization, the differ- entiation between victimized and revictimized individuals, as well as the investigation of re-victimization in a severly impaired sample. Strength of study IV is the implicit measure of guilt and shame in association with trauma and PTSD. A Limitation is the cross-sectional design of both empirical studies which does not allow causal relationships to be drawn. Overall, results indicate, that non-increased risk recognition in interpersonally victimized indi-viduals in combination with increased attachment anxiety and state- dissociation, as well as decreased self-efficacy can increase the risk for revictimization. To prevent revictimization these risk factors should be considered in the treatment of interpersonally traumatized indi-viduals. An increased risk recognition may be interpreted as a protective factor regarding revictimization. Furthermore, results indicate that in addition to trauma- related guilt and shame, generalized explicit guilt- and shame and an implicit guilt-prone self-concept seems to play a crucial role in PTSD. This should be considered in treating patients with PTSD
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