Vermarktungsstrategie für endverbraucherorientierte Leistungen: Konzeption für Anbieter des Gesundheitstourismus

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Transdiagnostic phenomena of psychopathology in the context of the RDoC: protocol of a multimodal cross-sectional study

In the past, affective and cognitive processes related to psychopathology have been examined within the boundaries of phenotype-based diagnostic labels, which has led to inconsistent findings regarding their underlying operating principles. Investigating these processes dimensionally in healthy individuals and by means of multiple modalities may provide additional insights into the psychological and neuronal mechanisms at their core. The transdiagnostic phenomena Neuroticism and Rumination are known to be closely linked. However, the exact nature of their relationship remains to be elucidated. The same applies to the associations between Hedonic Capacity, Negativity Bias and different Emotion Regulation strategies. This multimodal cross-sectional study examines the relationship of the transdiagnostic phenomena Neuroticism and Rumination as well as Hedonic Capacity, the Negativity Bias and Emotion Regulation from a RDoC (Research Domain Criteria) perspective. A total of 120 currently healthy subjects (past 12 months) will complete several questionnaires regarding personality, emotion regulation, hedonic capacity, and psychopathologies as well as functional magnetic resonance imaging (fMRI) during cognitive and emotional processing, to obtain data on the circuit, behavioral and self-report level. This study aims to contribute to the understanding of the relationship between cognitive and affective processes associated with psychopathologies as well as their neuronal correlates. Ultimately, a grounded understanding of these processes could guide improvement of diagnostic labels and treatments. Limitations include the cross-sectional design and the limited variability in psychopathology scores due to the restriction of the sample to currently healthy subjects

L'Islam en Adjarie : trajectoire historique et implications contemporaines

Après des décennies d'interdits, dans un contexte politique et culturel marqué par une grande difficulté à accepter la différence religieuse, cette étude est l'une des toutes premières à s'attaquer à la question de l'Islam au sein de la nation géorgienne. Dans sa partie historique, elle s`appuie essentiellement sur les sources géorgiennes. Pour l'auteur, exploiter les travaux et les témoignages des chercheurs et des voyageurs géorgiens de la seconde moitié du XIXe siècle est essentiel. Cela lui permet non seulement d'approcher des sources jusque-là inédites ou tabou, mais aussi de mieux cerner les représentations géorgiennes des Géorgiens musulmans, en particulier des Adjars, dans une Géorgie alors engagée dans la construction / reconstruction de son histoire. Toutefois un certain nombre de ces sources, en particulier Zakaria Cicinadze, sont aujourd'hui l'objet de vives discussions et de critiques en Géorgie

L'Islam en Adjarie : trajectoire historique et implications contemporaines

Après des décennies d'interdits, dans un contexte politique et culturel marqué par une grande difficulté à accepter la différence religieuse, cette étude est l'une des toutes premières à s'attaquer à la question de l'Islam au sein de la nation géorgienne. Dans sa partie historique, elle s`appuie essentiellement sur les sources géorgiennes. Pour l'auteur, exploiter les travaux et les témoignages des chercheurs et des voyageurs géorgiens de la seconde moitié du XIXe siècle est essentiel. Cela lui permet non seulement d'approcher des sources jusque-là inédites ou tabou, mais aussi de mieux cerner les représentations géorgiennes des Géorgiens musulmans, en particulier des Adjars, dans une Géorgie alors engagée dans la construction / reconstruction de son histoire. Toutefois un certain nombre de ces sources, en particulier Zakaria Cicinadze, sont aujourd'hui l'objet de vives discussions et de critiques en Géorgie

Between-strand disulfides: Forbidden disulfides linking adjacent ß-Strands

Between-strand disulfides (BSDs) connect cysteine (Cys) residues across adjacent strands of β-sheets. There are four BSD types which can be found in regular β-structure: CSDs, which link residues immediately opposite each other in the β-structure (residues i and j); ETDs, which connect Cys out of register by one residue (i and j ± 1); BDDs, which join Cys at positions i and j ± 2; and BFDs, which link residues i and j ± 3. Formation of these disulfides was initially predicted to be forbidden, producing too much local strain in the protein fold. However, BSDs do exist in nature. Significantly, their high levels of strain allow them to be involved in redox processes under physiological conditions. Here we characterise BSD motifs found in the Protein Data Bank (PDB), discussing important intrinsic factors, such as the disulfide conformation and torsional strain, and extrinsic factors, such as the influence of the β-sheet environment on the disulfide and vice versa. We also discuss the biological importance of BSDs, including the prevalence of non-homologous examples in the PDB, the conservation of BSD motifs amongst related proteins (BSD clusters) and experimental evidence for BSD redox activity. For clusters of homologous BSDs we present detailed data of the disulfide properties and the variations of these properties amongst the “redundant” structures. Identification of disulfides with the potential to be involved in biological redox processes via the analysis of these data will provide important insights into the function and mechanism of BSD-containing proteins. Characterisation of thiol-based redox signalling pathways will lead to significant breakthroughs in understanding the molecular basis of oxidative stress and associated pathways, such as ageing and neurodegenerative diseases

Insights into the evolutionary origins of clostridial neurotoxins from analysis of the Clostridium botulinum strain A neurotoxin gene cluster

<p>Abstract</p> <p>Background</p> <p>Clostridial neurotoxins (CNTs) are the most deadly toxins known and causal agents of botulism and tetanus neuroparalytic diseases. Despite considerable progress in understanding CNT structure and function, the evolutionary origins of CNTs remain a mystery as they are unique to <it>Clostridium </it>and possess a sequence and structural architecture distinct from other protein families. Uncovering the origins of CNTs would be a significant contribution to our understanding of how pathogens evolve and generate novel toxin families.</p> <p>Results</p> <p>The <it>C. botulinum </it>strain A genome was examined for potential homologues of CNTs. A key link was identified between the neurotoxin and the flagellin gene (CBO0798) located immediately upstream of the BoNT/A neurotoxin gene cluster. This flagellin sequence displayed the strongest sequence similarity to the neurotoxin and NTNH homologue out of all proteins encoded within <it>C. botulinum </it>strain A. The CBO0798 gene contains a unique hypervariable region, which in closely related flagellins encodes a collagenase-like domain. Remarkably, these collagenase-containing flagellins were found to possess the characteristic HEXXH zinc-protease motif responsible for the neurotoxin's endopeptidase activity. Additional links to collagenase-related sequences and functions were detected by further analysis of CNTs and surrounding genes, including sequence similarities to collagen-adhesion domains and collagenases. Furthermore, the neurotoxin's HCRn domain was found to exhibit both structural and sequence similarity to eukaryotic collagen jelly-roll domains.</p> <p>Conclusion</p> <p>Multiple lines of evidence suggest that the neurotoxin and adjacent genes evolved from an ancestral collagenase-like gene cluster, linking CNTs to another major family of clostridial proteolytic toxins. Duplication, reshuffling and assembly of neighboring genes within the BoNT/A neurotoxin gene cluster may have lead to the neurotoxin's unique architecture. This work provides new insights into the evolution of <it>C. botulinum </it>neurotoxins and the evolutionary mechanisms underlying the origins of virulent genes.</p

Region- and time- specific effects of ketamine on cerebral blood flow: a randomized controlled trial

There is intriguing evidence suggesting that ketamine might have distinct acute and delayed neurofunctional effects, as its acute administration transiently induces schizophrenia-like symptoms, while antidepressant effects slowly emerge and are most pronounced 24 h after administration. Studies attempting to characterize ketamine’s mechanism of action by using blood oxygen level dependent (BOLD) imaging have yielded inconsistent results regarding implicated brain regions and direction of effects. This may be due to intrinsic properties of the BOLD contrast, while cerebral blood flow (CBF), as measured with arterial spin labeling, is a single physiological marker more directly related to neural activity. As effects of acute ketamine challenge are sensitive to modulation by pretreatment with lamotrigine, which inhibits glutamate release, a combination of these approaches should be particularly suited to offer novel insights. In total, 75 healthy participants were investigated in a double blind, placebo-controlled, randomized, parallel-group study and underwent two scanning sessions (acute/post 24 h.). Acute ketamine administration was associated with higher perfusion in interior frontal gyrus (IFG) and dorsolateral prefrontal cortex (DLPFC), but no other investigated brain region. Inhibition of glutamate release by pretreatment with lamotrigine abolished ketamine’s effect on perfusion. At the delayed time point, pretreatment with lamotrigine was associated with lower perfusion in IFG. These findings underscore the idea that regionally selective patterns of CBF changes reflect proximate effects of modulated glutamate release on neuronal activity. Furthermore, region- specific sustained effects indicate both a swift restoration of disturbed homeostasis in DLPFC as well changes occurring beyond the immediate effects on glutamate signaling in IFG

Modulatory Effects of Ketamine and Lamotrigine on Cognition: Emotion Interaction in the Brain

Introduction: Cognition and emotion are fundamentally integrated in the brain and mutually contribute to behavior. The relation between working memory (WM) and emotion is particularly suited to investigate cognition-emotion interaction since WM is an essential component of many higher cognitive functions. Ketamine affects not only WM but also has a profound impact on emotional processing. Effects of acute ketamine challenge are sensitive to modulation by pretreatment with lamotrigine, which inhibits glutamate release. Accordingly, a combination of these approaches should be particularly suited to investigate cognition-emotion interaction. Methods: Seventy five healthy subjects were investigated in a double-blind, placebo-controlled, randomized, single-dose, parallel-group study with three treatment conditions. All subjects underwent two scanning sessions (acute/post 24 h). Results: Compared to placebo, acute ketamine administration induced significant dissociative, psychotomimetic, and cognitive effects, as well as an increase in neural activity during WM for positive stimuli. Inhibition of glutamate release by pretreatment with lamotrigine did not influence ketamine's subjective effects, but significantly attenuated its impact on emotional WM and associated neural activity. There was no effect on these measures 24 h after ketamine administration. Conclusion: Our results demonstrate differential acute effects of modulated glutamate release and a swift restoration of disturbed neurobehavioral homeostasis in healthy subjects