bluuebunny/crossref_metadata_2025_split huggingface dataset:
Betriebliches Gesundheitsmanagement – ein neuer Baustein des Gesundheitstourismus oder vice versa?
Authors: Heuwinkel Kerstin 
Published: February 2016

Zusammenfassung
Gegenstand des Beitrags ist die Ein- bzw. Abgrenzung des Gesundheitstourismus im Hinblick auf die Entwicklungen der Nachfrage, die durch betriebliches Gesundheitsmanagement (BGM) vor dem Hintergrund gesellschaftlicher Entwicklungen induziert wird. In einem ersten Schritt werden die Begriffe Gesundheits- und Medizintourismus voneinander abgegrenzt und in eine Typologie überführt. Dem folgt eine Darstellung wesentlicher Aspekte des betrieblichen Gesundheitsmanagements. Neben der Entwicklung des BGM werden vor allem extern durchführbare Maßnahmen vorgestellt. Zentral ist eine strukturierte Betrachtung solcher Maßnahmen, da diese gesundheitstouristisch relevant sind. Der Beitrag endet mit einer Darstellung strategischer Ansätze für gesundheitstouristische Akteure und einer kritischen Betrachtung.
Tourismus und Integriertes Wasserressourcenmanagement am Zayandeh Rud
Authors: Davoudi Arash , Schramm Engelbert 
Published: February 2016

Zusammenfassung
Im Rahmen eines Verbundvorhabens zum Integrierten Wassermanagement wird der Tourismus als wichtiger Sektor betrachtet. Das Einzugsgebiet des Flusses Zayandeh Rud im Zentrum von Iran weist trotz vorhandener Defizite aufgrund seiner einzigartigen Kulturerbe, der ausgezeichneten klimatischen und natürlichen Bedingungen, der guten Lage und seiner langjährigen „Tourismuskultur“ ein sehr großes Potenzial zur Intensivierung insbesondere der unterschiedlichen Formen des nachhaltigen Tourismus auf. Diese werden nicht nur Risiken für die Nutzung des Zayandeh Rud darstellen, sondern auch Chancen für ein nachhaltiges und zugleich integriertes Management seiner Wasserressourcen bieten. Entfaltete Potenziale und die Entwicklung eines nachhaltigen Tourismus können zur Verbesserung der Lebensbedingungen der dort lebenden Menschen, zum Schutz der Umwelt und des Kulturerbes führen.
Nutzen von Gütesiegeln für touristische Anbieter von Wellnessleistungen
Authors: Voshage Ina 
Published: February 2016

Zusammenfassung
Gütesiegel sind ein Versuch, angebotene Wellnessleistungen transparenter und vergleichbarer zu machen und dem Kunden die Kaufentscheidung zu erleichtern. Der vorliegende Artikel stellt dar, welchen Nutzen Gütesiegel für touristische Anbieter von Wellnessleistungen haben. Anhand der Phasenorientierung im Tourismus wird der Nutzen als Marketing-Instrument, der Nutzen für das Qualitätsmanagement und der Nutzen für die Kundenbindung beurteilt. Die daraus abgeleiteten Handlungsempfehlungen zeigen auf, wie der Nutzen von Wellness-Gütesiegeln erhöht werden könnte. Der Artikel basiert auf einer Bachelorarbeit an der Hochschule Harz.
History is Divine Art: Schelling’s Spätphilosophie as Orthodox Romantic Theology
Authors: Medley George H. 
Published: February 2016

AbstractSchelling’s Spätphilosophie is largely neglected in the non-German academy, and where it is addressed, it is usually minimized or misrepresented. It is the contention of this paper that, rather than a final unremarkable departure from his prior philosophical work, Schelling’s Spätphilosophie, and not Hegel’s work, represents the culmination of German idealism. Further, this culmination puts Schelling more directly in dialogue with Romanticism than his previous work had done, while simultaneously guiding him in what might be termed a broadly orthodox direction. By understanding God as entering into a dynamic relationship with humanity to reveal ultimate truth through the medium of history, Schelling’s Spätphilosophie represents a reworking of his earlier Identity Philosophy in a more intentionally Romantic position to yield a definitive Romantic Theology.
Aβ40 Reduces P-Glycoprotein at the Blood–Brain Barrier through the Ubiquitin–Proteasome Pathway
Authors: Hartz Anika M.S. , Zhong Yu , Wolf Andrea , LeVine Harry , Miller David S. , Bauer Björn 
Published: February 2016

Failure to clear amyloid-β (Aβ) from the brain is in part responsible for Aβ brain accumulation in Alzheimer's disease (AD). A critical protein for clearing Aβ across the blood–brain barrier is the efflux transporter P-glycoprotein (P-gp) in the luminal plasma membrane of the brain capillary endothelium. P-gp is reduced at the blood–brain barrier in AD, which has been shown to be associated with Aβ brain accumulation. However, the mechanism responsible for P-gp reduction in AD is not well understood. Here we focused on identifying critical mechanistic steps involved in reducing P-gp in AD. We exposed isolated rat brain capillaries to 100 nmAβ40, Aβ40, aggregated Aβ40, and Aβ42. We observed that only Aβ40 triggered reduction of P-gp protein expression and transport activity levels; this occurred in a dose- and time-dependent manner. To identify the steps involved in Aβ-mediated P-gp reduction, we inhibited protein ubiquitination, protein trafficking, and the ubiquitin–proteasome system, and monitored P-gp protein expression, transport activity, and P-gp-ubiquitin levels. Thus, exposing brain capillaries to Aβ40 triggers ubiquitination, internalization, and proteasomal degradation of P-gp. These findings may provide potential therapeutic targets within the blood–brain barrier to limit P-gp degradation in AD and improve Aβ brain clearance.SIGNIFICANCE STATEMENTThe mechanism reducing blood–brain barrier P-glycoprotein (P-gp) in Alzheimer's disease is poorly understood. In the present study, we focused on defining this mechanism. We demonstrate that Aβ40 drives P-gp ubiquitination, internalization, and proteasome-dependent degradation, reducing P-gp protein expression and transport activity in isolated brain capillaries. These findings may provide potential therapeutic avenues within the blood–brain barrier to limit P-gp degradation in Alzheimer's disease and improve Aβ brain clearance.
Distinct Mechanisms for Distractor Suppression and Target Facilitation
Authors: Noonan MaryAnn P. , Adamian Nika , Pike Alexandra , Printzlau Frida , Crittenden Ben M. , Stokes Mark G. 
Published: February 2016

It is well established that preparatory attention improves processing of task-relevant stimuli. Although it is often more important to ignore task-irrelevant stimuli, comparatively little is known about preparatory attentional mechanisms for inhibiting expected distractions. Here, we establish that distractor inhibition is not under the same top-down control as target facilitation. Using a variant of the Posner paradigm, participants were cued to either the location of a target stimulus, the location of a distractor, or were provided no predictive information. In Experiment 1, we found that participants were able to use target-relevant cues to facilitate target processing in both blocked and flexible conditions, but distractor cueing was only effective in the blocked version of the task. In Experiment 2, we replicate these findings in a larger sample and leveraged the additional statistical power to perform individual differences analyses to tease apart potential underlying mechanisms. We found no evidence for a correlation between these two types of benefit, suggesting that flexible target cueing and distractor suppression depend on distinct cognitive mechanisms. In Experiment 3, we use EEG to show that preparatory distractor suppression is associated with a diminished P1, but we found no evidence to suggest that this effect was mediated by top-down control of oscillatory activity in the alpha band (8–12 Hz). We conclude that flexible top-down mechanisms of cognitive control are specialized for target-related attention, whereas distractor suppression only emerges when the predictive information can be derived directly from experience. This is consistent with a predictive coding model of expectation suppression.SIGNIFICANCE STATEMENTIf you were told to ignore a white bear, you might find it quite difficult. Holding something in working memory is thought to automatically facilitate feature processing, even if doing so is detrimental to the current task. Despite this paradox, it is often assumed that distractor suppression is controlled via similar top-down mechanisms of attention that prepare brain areas for target enhancement. In particular, low-frequency oscillations in visual cortex appear especially well suited for gating task-irrelevant information. We describe the results of a series of studies exploring distractor suppression and challenge this popular notion. We draw on behavioral and EEG evidence to show that selective distractor suppression operates via an alternative mechanism, such as expectation suppression within a predictive coding framework.
Altered Trafficking and Processing ofGALCMutants Correlates with Globoid Cell Leukodystrophy Severity
Authors: Shin Daesung , Feltri M. Laura , Wrabetz Lawrence 
Published: February 2016

Globoid cell leukodystrophy (GLD, Krabbe disease) is due to autosomal recessive mutations in the lysosomal enzyme galactosylceramidase (GALC). Many GLD patients develop infantile-onset of progressive neurologic deterioration and death by 2 years of age, whereas others have a later-onset, milder disease. Cord blood transplant slows disease progression much more effectively when performed presymptomatically, highlighting the importance of early diagnosis. Current diagnosis is based on reduced GALC activity, DNA sequence, and clinical examination. However, presymptomatic diagnosis is hampered by imperfect genotype-GALC activity-phenotype correlations. In addition, three polymorphisms in theGALCgene are variably associated with disease mutations and have unknown effects on GALC activity and disease outcome. Here, we study mutations that cause infantile or later-onset GLD, and show that GALC activity is significantly lower in infantile versus later-onset mutants when measured in the lysosomal fraction, but not in whole-cell lysates. In parallel, infantile-onset mutant GALCs showed reduced trafficking to lysosomes and processing than later-onset mutant GALCs. Finally, thecis-polymorphisms also affected trafficking to the lysosome and processing of GALC. These differences potentially explain why the activity of different mutations appears similar in whole-cell extracts from lymphocytes, and suggest that measure of GALC activity in lysosomes may better predict the onset and severity of disease for a given GLD genotype.SIGNIFICANCE STATEMENTGloboid cell leukodystrophy (GLD, Krabbe disease) is diagnosed by measuring galactosylceramidase (GALC) activity and DNA analysis. However, genotype and phenotype often do not correlate due to considerable clinical variability, even for the same mutation, for unknown reasons. We find that altered trafficking to the lysosome and processing of GALC correlates with GLD severity and is modulated bycis-polymorphisms. Current diagnosis of GLD is based on GALC activity of total cell lysates from blood, which does not discriminate whether the activity comes from the lysosome or other subcellular organelles. Measurement of GALC activity in lysosomes may predict which infants are at high risk for the infantile phenotype while distinguishing other children who will develop later-onset phenotypes without onset of symptoms for years.
Temporal Asymmetry in Dark–Bright Processing Initiates Propagating Activity across Primary Visual Cortex
Authors: Rekauzke Sascha , Nortmann Nora , Staadt Robert , Hock Howard S. , Schöner Gregor , Jancke Dirk 
Published: February 2016

Differences between visual pathways representing darks and lights have been shown to affect spatial resolution and detection timing. Both psychophysical and physiological studies suggest an underlying retinal origin with amplification in primary visual cortex (V1). Here we show that temporal asymmetries in the processing of darks and lights create motion in terms of propagating activity across V1. Exploiting the high spatiotemporal resolution of voltage-sensitive dye imaging, we captured population responses to abrupt local changes of luminance in cat V1. For stimulation we used two neighboring small squares presented on either bright or dark backgrounds. When a single square changed from dark to bright or vice versa, we found coherent population activity emerging at the respective retinal input locations. However, faster rising and decay times were obtained for the bright to dark than the dark to bright changes. When the two squares changed luminance simultaneously in opposite polarities, we detected a propagating wave front of activity that originated at the cortical location representing the darkened square and rapidly expanded toward the region representing the brightened location. Thus, simultaneous input led to sequential activation across cortical retinotopy. Importantly, this effect was independent of the squares' contrast with the background. We suggest imbalance in dark–bright processing as a driving force in the generation of wave-like activity. Such propagation may convey motion signals and influence perception of shape whenever abrupt shifts in visual objects or gaze cause counterchange of luminance at high-contrast borders.SIGNIFICANCE STATEMENTAn elementary process in vision is the detection of darks and lights through the retina via ON and OFF channels. Psychophysical and physiological studies suggest that differences between these channels affect spatial resolution and detection thresholds. Here we show that temporal asymmetries in the processing of darks and lights create motion signals across visual cortex. Using two neighboring squares, which simultaneously counterchanged luminance, we discovered propagating activity that was strictly drawn out from cortical regions representing the darkened location. Thus, a synchronous stimulus event translated into sequential wave-like brain activation. Such propagation may convey motion signals accessible in higher brain areas, whenever abrupt shifts in visual objects or gaze cause counterchange of luminance at high-contrast borders.
β-Amyloid Deposition Is Associated with Decreased Right Prefrontal Activation during Task Switching among Cognitively Normal Elderly
Authors: Oh Hwamee , Steffener Jason , Razlighi Qolamreza R. , Habeck Christian , Stern Yaakov 
Published: February 2016

The accumulation of β-amyloid (Aβ) peptides, a pathological hallmark of Alzheimer's disease (AD), has been associated with functional alterations, often in an episodic memory system with a particular emphasis on medial temporal lobe function. The topography of Aβ deposition, however, largely overlaps with frontoparietal control (FPC) regions implicated in cognitive control that has been shown to be impaired in early mild AD. To understand the neural mechanism underlying early changes in cognitive control with AD, we examined the impact of Aβ deposition on task-evoked FPC activation using functional magnetic resonance imaging (fMRI) in humans. Forty-three young and 62 cognitively normal older adults underwent an fMRI session during an executive contextual task in which task difficulty varied: single (either letter case or vowel/consonant judgment task) vs dual (switching between letter case and vowel/consonant decisions) task. Older subjects additionally completed18F-florbetaben positron emission tomography scans and were classified as either amyloid positive (Aβ+) or negative (Aβ−). Consistent with previous reports, age-related increases in brain activity were found in FPC regions commonly identified across groups. For both task conditions, Aβ-related increases in brain activity were found compared with baseline activity. For higher cognitive control load, however, Aβ+ elderly showed reduced task-switching activation in the right inferior frontal cortex. Our findings suggest that with Aβ deposition, brain activation in the cognitive control region reaches a maximum with lower control demand and decreases with higher control demand, which may underlie early impairment in cognitive control with AD progression.SIGNIFICANCE STATEMENTThe accumulation of β-amyloid (Aβ) peptides, a pathological hallmark of Alzheimer's disease, spatially overlaps with frontoparietal control (FPC) regions implicated in cognitive control, but the impact of Aβ deposition on FPC regions is largely unknown. Using functional magnetic resonance imaging with a task-switching task, we found Aβ-related increases in FPC regions compared with baseline activity. For higher cognitive control load, however, Aβ-related hypoactivity was found in the right inferior frontal cortex, a region highly implicated in cognitive control. The findings suggest that with Aβ deposition, task-related brain activity may reach a plateau early and undergo downstream pathways of neural dysfunction, which may relate to the early impairment of cognitive control seen in the progression of Aβ pathology.
Multifaceted Contributions by Different Regions of the Orbitofrontal and Medial Prefrontal Cortex to Probabilistic Reversal Learning
Authors: Dalton Gemma L. , Wang Nena Y. , Phillips Anthony G. , Floresco Stan B. 
Published: February 2016

Different subregions of the prefrontal cortex (PFC) contribute to the ability to respond flexibly to changes in reward contingencies, with the medial versus orbitofrontal cortex (OFC) subregions contributing differentially to processes such as set-shifting and reversal learning. To date, the manner in which these regions may facilitate reversal learning in situations involving reward uncertainty remains relatively unexplored. We investigated the involvement of five distinct regions of the rat OFC (lateral and medial) and medial PFC (prelimbic, infralimbic, and anterior cingulate) on probabilistic reversal learning wherein “correct” versus “incorrect” responses were rewarded on 80% and 20% of trials, respectively. Contingencies were reversed repeatedly within a session. In well trained rats, inactivation of the medial or lateral OFC induced dissociable impairments in performance (indexed by fewer reversals completed) when outcomes were probabilistic, but not when they were assured. Medial OFC inactivation impaired probabilistic learning during the first discrimination, increased perseverative responding and reduced sensitivity to positive and negative feedback, suggestive of a deficit in incorporating information about previous action outcomes to guide subsequent behavior. Lateral OFC inactivation preferentially impaired performance during reversal phases. In contrast, prelimbic inactivation caused an apparent improvement in performance by increasing the number of reversals completed. This was associated with enhanced sensitivity to recently rewarded actions and reduced sensitivity to negative feedback. Infralimbic inactivation had no effect, whereas the anterior cingulate appeared to play a permissive role in this form of reversal learning. These results clarify the dissociable contributions of different regions of the frontal lobes to probabilistic learning.SIGNIFICANCE STATEMENTThe ability to adjust behavior in response to changes involving uncertain or probabilistic reward contingencies is an essential survival skill that is impaired in a variety of psychiatric disorders. It is well established that different forms of cognitive flexibility are mediated by anatomically distinct regions of the frontal lobes when reinforcement contingencies are assured, however, less is known about the contribution of these regions to probabilistic reinforcement learning. Here we show that different regions of the orbitofrontal and medial prefrontal cortex make distinct contributions to probabilistic reversal learning. These findings provide novel information about the complex interplay between frontal lobe regions in mediating these processes and accordingly provide insight into possible pathophysiology that underlies impairments in cognitive flexibility observed in mental illnesses.
Shawn, theDrosophilaHomolog of SLC25A39/40, Is a Mitochondrial Carrier That Promotes Neuronal Survival
Authors: Slabbaert Jan R. , Kuenen Sabine , Swerts Jef , Maes Ine , Uytterhoeven Valerie , Kasprowicz Jaroslaw , Fernandes Ana Clara , Blust Ronny , Verstreken Patrik 
Published: February 2016

Mitochondria play an important role in the regulation of neurotransmission, and mitochondrial impairment is a key event in neurodegeneration. Cells rely on mitochondrial carrier proteins of the SLC25 family to shuttle ions, cofactors, and metabolites necessary for enzymatic reactions. Mutations in these carriers often result in rare but severe pathologies in the brain, and some of the genes, includingSLC25A39andSLC25A40, reside in susceptibility loci of severe forms of epilepsy. However, the role of most of these carriers has not been investigated in neuronsin vivo. We identifiedshawn, theDrosophilahomolog ofSLC25A39andSLC25A40, in a genetic screen to identify genes involved in neuronal function. Shawn localizes to mitochondria, and missense mutations result in an accumulation of reactive oxygen species, mitochondrial dysfunction, and neurodegeneration. Shawn regulates metal homeostasis, and we found inshawnmutants increased levels of manganese, calcium, and mitochondrial free iron. Mitochondrial mutants often cannot maintain synaptic transmission under demanding conditions, but shawnmutants do, and they also do not display endocytic defects. In contrast,shawnmutants harbor a significant increase in neurotransmitter release. Our work provides the first functional annotation of these essential mitochondrial carriers in the nervous system, and the results suggest that metal imbalances and mitochondrial dysfunction may contribute to defects in synaptic transmission and neuronal survival.SIGNIFICANCE STATEMENTWe describe for the first time the role of the mitochondrial carrier Shawn/SLC25A39/SLC25A40 in the nervous system. In humans, these genes reside in susceptibility loci for epilepsy, and, in flies, we observe neuronal defects related to mitochondrial dysfunction and metal homeostasis defects. Interestingly,shawnmutants also harbor increased neurotransmitter release and neurodegeneration. Our data suggest a connection between maintaining a correct metal balance and mitochondrial function to regulate neuronal survival and neurotransmitter release.