bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Krüppel-Like Factor Dar1 Determines Multipolar Neuron Morphology
Authors: Wang Xin , Zhang Macy W. , Kim Jung Hwan , Macara Ann Marie , Sterne Gabriella , Yang Tao , Ye Bing 
Published: October 2015

Neurons typically assume multipolar, bipolar, or unipolar morphologies. Little is known about the mechanisms underlying the development of these basic morphological types. Here, we show that the Krüppel-like transcription factor Dar1 determines the multipolar morphology of postmitotic neurons inDrosophila. Dar1 is specifically expressed in multipolar neurons and loss ofdar1gradually converts multipolar neurons into the bipolar or unipolar morphology without changing neuronal identity. Conversely, misexpression of Dar1 or its mammalian homolog in unipolar and bipolar neurons causes them to assume multipolar morphologies. Dar1 regulates the expression of several dynein genes andnuclear distribution protein C(nudC), which is an essential component of a specialized dynein complex that positions the nucleus in a cell. We further show that these genes are required for Dar1-induced multipolar neuron morphology.Dar1likely functions as a terminal selector gene for the basic layout of neuron morphology by regulating both dendrite extension and the dendrite–nucleus coupling.SIGNIFICANCE STATEMENTThe three basic morphological types of neurons—unipolar, bipolar, and multipolar—are important for information processing and wiring of neural circuits. Little progress has been made toward understanding the molecular and cellular programs that generate these types since their discovery over a century ago. It is generally assumed that basic morphological types of neurons are determined by the number of dendrites growing out from the cell body. Here, we show that this model alone is insufficient. We introduce the positioning of nucleus as a critical factor in this process and report that the transcription factor Dar1 determines multipolar neuron morphology in postmitotic neurons by regulating genes involved in nuclear positioning.
Frizzled3 Controls Axonal Polarity and Intermediate Target Entry during Striatal Pathway Development
Authors: Morello Francesca , Prasad Asheeta A. , Rehberg Kati , Vieira de Sá Renata , Antón-Bolaños Noelia , Leyva-Diaz Eduardo , Adolfs Youri , Tissir Fadel , López-Bendito Guillermina , Pasterkamp R. Jeroen 
Published: October 2015

The striatum is a large brain nucleus with an important role in the control of movement and emotions. Medium spiny neurons (MSNs) are striatal output neurons forming prominent descending axon tracts that target different brain nuclei. However, how MSN axon tracts in the forebrain develop remains poorly understood. Here, we implicate the Wnt binding receptor Frizzled3 in several uncharacterized aspects of MSN pathway formation [i.e., anterior–posterior guidance of MSN axons in the striatum and their subsequent growth into the globus pallidus (GP), an important (intermediate) target]. InFrizzled3knock-out mice, MSN axons fail to extend along the anterior–posterior axis of the striatum, and many do not reach the GP. Wnt5a acts as an attractant for MSN axonsin vitro, is expressed in a posterior high, anterior low gradient in the striatum, andWnt5aknock-out mice phenocopy striatal anterior–posterior defects observed inFrizzled3mutants. This suggests that Wnt5a controls anterior–posterior guidance of MSN axons through Frizzled3. Axons that reach the GP inFrizzled3knock-out mice fail to enter this structure. Surprisingly, entry of MSN axons into the GP non–cell-autonomously requires Frizzled3, and our data suggest that GP entry may be contingent on the correct positioning of “corridor” guidepost cells for thalamocortical axons by Frizzled3. Together, these data dissect MSN pathway development and reveal (non)cell-autonomous roles for Frizzled3 in MSN axon guidance. Further, they are the first to identify a gene that provides anterior–posterior axon guidance in a large brain nucleus and link Frizzled3 to corridor cell development.SIGNIFICANCE STATEMENTStriatal axon pathways mediate complex physiological functions and are an important therapeutic target, underscoring the need to define how these connections are established. Remarkably, the molecular programs regulating striatal pathway development remain poorly characterized. Here, we determine the embryonic ontogeny of the two main striatal pathways (striatonigral and striatopallidal) and identify novel (non)cell-autonomous roles for the axon guidance receptor Frizzled3 in uncharacterized aspects of striatal pathway formation (i.e., anterior–posterior axon guidance in the striatum and axon entry into the globus pallidus). Further, our results link Frizzled3 to corridor guidepost cell development and suggest that an abnormal distribution of these cells has unexpected, widespread effects on the development of different axon tracts (i.e., striatal and thalamocortical axons).
A Post-Docking Role of Synaptotagmin 1-C2B Domain Bottom Residues R398/399 in Mouse Chromaffin Cells
Authors: Kedar Girish H. , Munch Anders S. , van Weering Jan R.T. , Malsam Jörg , Scheutzow Andrea , de Wit Heidi , Houy Sébastien , Tawfik Bassam , Söllner Thomas H. , Sørensen Jakob B. , Verhage Matthijs 
Published: October 2015

Synaptotagmin-1 (Syt1) is the principal Ca2+sensor for vesicle fusion and is also essential for vesicle docking in chromaffin cells. Docking depends on interactions of the Syt1-C2B domain with the t-SNARE SNAP25/Syntaxin1 complex and/or plasma membrane phospholipids. Here, we investigated the role of the positively charged “bottom” region of the C2B domain, proposed to help crosslink membranes, in vesicle docking and secretion in mouse chromaffin cells and in cell-free assays. We expressed a double mutation shown previously to interfere with lipid mixing between proteoliposomes and with synaptic transmission, Syt1-R398/399Q (RQ), insyt1null mutant cells. Ultrastructural morphometry revealed that Syt1-RQ fully restored the docking defect observed previously insyt1null mutant cells, similar to wild type Syt1 (Syt1-wt). Small unilamellar lipid vesicles (SUVs) that contained the v-SNARE Synaptobrevin2 and Syt1-R398/399Q also docked to t-SNARE-containing giant vesicles (GUVs), similar to Syt1-wt. However, unlike Syt1-wt, Syt1-RQ-induced docking was strictly PI(4,5)P2-dependent. Unlike docking, neither synchronized secretion in chromaffin cells nor Ca2+-triggered SUV–GUV fusion was restored by the Syt1 mutants. Finally, overexpressing the RQ-mutant inwild typecells produced no effect on either docking or secretion. We conclude that the positively charged bottom region in the C2B domain—and, by inference, Syt1-mediated membrane crosslinking—is required for triggering fusion, but not for docking. Secretory vesicles dock by multiple, PI(4,5)P2-dependent and PI(4,5)P2-independent mechanisms. The R398/399 mutations selectively disrupt the latter and hereby help to discriminate protein regions involved in different aspects of Syt1 function in docking and fusion.SIGNIFICANCE STATEMENTThis study provides new insights in how the two opposite sides of the C2B domain of Synaptotagmin-1 participate in secretory vesicle fusion, and in more upstream steps, especially vesicle docking. We show that the “bottom” surface of the C2B domain is required for triggering fusion, but not for docking. Synaptotagmin-1 promotes docking by multiple, PI(4,5)P2-dependent and PI(4,5)P2-independent mechanisms. Mutations in the C2B bottom surface (R398/399) selectively disrupt the latter. These mutations help to discriminate protein regions involved in different aspects of Synaptotagmin-1 function in docking and fusion.
Distinct Contributions of Ventromedial and Dorsolateral Subregions of the Human Substantia Nigra to Appetitive and Aversive Learning
Authors: Pauli Wolfgang M. , Larsen Tobias , Collette Sven , Tyszka Julian M. , Seymour Ben , O'Doherty John P. 
Published: October 2015

The role of neurons in the substantia nigra (SN) and ventral tegmental area (VTA) of the midbrain in contributing to the elicitation of reward prediction errors during appetitive learning has been well established. Less is known about the differential contribution of these midbrain regions to appetitive versus aversive learning, especially in humans. Here we scanned human participants with high-resolution fMRI focused on the SN and VTA while they participated in a sequential Pavlovian conditioning paradigm involving an appetitive outcome (a pleasant juice), as well as an aversive outcome (an unpleasant bitter and salty flavor). We found a degree of regional specialization within the SN: Whereas a region of ventromedial SN correlated with a temporal difference reward prediction error during appetitive Pavlovian learning, a dorsolateral area correlated instead with an aversive expected value signal in response to the most distal cue, and to a reward prediction error in response to the most proximal cue to the aversive outcome. Furthermore, participants' affective reactions to both the appetitive and aversive conditioned stimuli more than 1 year after the fMRI experiment was conducted correlated with activation in the ventromedial and dorsolateral SN obtained during the experiment, respectively. These findings suggest that, whereas the human ventromedial SN contributes to long-term learning about rewards, the dorsolateral SN may be particularly important for long-term learning in aversive contexts.SIGNIFICANCE STATEMENTThe role of the substantia nigra (SN) and ventral tegmental area (VTA) in appetitive learning is well established, but less is known about their contribution to aversive compared with appetitive learning, especially in humans. We used high-resolution fMRI to measure activity in the SN and VTA while participants underwent higher-order Pavlovian learning. We found a regional specialization within the SN: a ventromedial area was selectively engaged during appetitive learning, and a dorsolateral area during aversive learning. Activity in these areas predicted affective reactions to appetitive and aversive conditioned stimuli over 1 year later. These findings suggest that, whereas the human ventromedial SN contributes to long-term learning about rewards, the dorsolateral SN may be particularly important for long-term learning in aversive contexts.
Influence of Tinnitus on Auditory Spectral and Temporal Resolution and Speech Perception in Tinnitus Patients
Authors: Moon Il Joon , Won Jong Ho , Kang Hyun Woo , Kim Dong Hyun , An Yong-Hwi , Shim Hyun Joon 
Published: October 2015

Although cochlear damage is believed to trigger the perception of tinnitus in the central auditory system, its pathophysiological mechanism is still unclear. We aimed to investigate the pathophysiology of tinnitus using psychoacoustic assessments of auditory spectral and temporal resolution and speech perception in noise. Human subjects with tinnitus and symmetric hearing thresholds were divided into three groups: nine unilateral tinnitus subjects with normal hearing thresholds (Group 1), 12 unilateral tinnitus subjects with hearing loss (HL; Group 2), and nine bilateral tinnitus subjects with HL. Fifteen normal-hearing subjects without tinnitus were also tested as a control group. Four different tests were administered: (1) the spectral-ripple discrimination (SRD) test, (2) the temporal modulation detection (TMD) test, (3) the Schroeder-phase discrimination (SPD) test, and (4) the speech recognition threshold (SRT) in noise test. There were no significant differences in SRD, TMD, and SPD between the tinnitus-affected ears (TEs) and non-tinnitus ears (NTEs) in Groups 1 and 2 (p> 0.05). In contrast, the TEs showed poorer SRTs than the NTEs in these two subject groups (p= 0.022 and 0.049). No inferiority of spectral/temporal resolution in TEs compared with NTEs suggests that there may be no more outer hair cell (OHC) damage on the tinnitus side given that damaged OHCs are associated with broadening the auditory filters. The decoupling of the SRT results from the spectral/temporal resolution data could imply that the occurrence of tinnitus does not depend upon the degree of damage to the OHCs, but rather upon different plastic changes in the central auditory system after cochlear damage.SIGNIFICANCE STATEMENTWe can easily find unilateral tinnitus patients who have symmetric hearing thresholds. Our research question was what kind of difference would be responsible for the tinnitus in the tinnitus-affected ears but not in the non-tinnitus ears of subjects with symmetric hearing thresholds. The answer to this fundamental question could help us to understand the pathophysiology of tinnitus. We evaluated the potential influence of tinnitus upon the subjects' auditory spectral and temporal resolution and speech perception in noise by comparing these psychoacoustic performances between tinnitus-affected ears and non-tinnitus ears in the same subjects.
Kommunale Swap-Verträge: Wirksamkeit und Beratungspflichten nach neuer BGH-Rechtsprechung
Authors: Lehmann Matthias 
Published: October 2015

Zusammenfassung
In seinem Urteil vom 28. 4. 2015 hat sich der BGH erstmals ausführlich mit kommunalen Swap-Verträgen befasst. Er nimmt deren grundsätzliche Wirksamkeit an. Neues gibt es auch für Swap-Verträge allgemein. Der BGH schränkt die Pflicht zur Aufklärung über den negativen Marktwert u. a. dann ein, wenn der Swap eine „konnexe“ Grundforderung absichert. Überraschend ist zudem, dass der BGH nicht mehr bei allen Derivateverträgen automatisch eine Beratungspflicht annimmt, sondern diese von den jeweiligen Vertragsklauseln abhängig macht. Außerdem nimmt er zu grundsätzlichen Fragen der Vorteilsausgleichung und der Verjährung bei verschiedenen Ansprüchen unter einem Rahmenvertrag Stellung.
How Risk-Return Efficient is the DAX 30? An Analysis of Risk Based Weighting Strategies
Authors: Grabellus Markus , Mager Ferdinand , Reinschmidt Timo 
Published: October 2015

Abstract
More than 25 years ago the DAX 30 was introduced as capitalization weighted performance index. We take a German perspective and replicate the DAX 30. We analyze alternative risk based weighting strategies using different minimum-variance estimators and low beta strategies. We find that the out-of-sample risk-return characteristics of the market capitalization weighted index can be substantially improved with quantitative portfolio selection rules. The results are robust to various specifications. They challenge the common practice of passive index investing and support recent trends of risk based investment strategies.
Predictors for chronic neck and low back pain in office workers: a 1‐year prospective cohort study
Authors: Sihawong Rattaporn , Sitthipornvorakul Ekalak , Paksaichol Arpalak , Janwantanakul Prawit 
Published: October 2015

Predictors for chronic neck and low back pain in office workers: a 1‐year prospective cohort study: Rattaporn Sihawong, et al. Faculty of Allied Health Sciences, Chulalongkorn University, ThailandObjectiveAll occupations expose workers to varied and unique conditions. The nature of work has been recognized as influencing the health of workers. Whether predictors for chronic neck and low back pain would be occupation‐specific is unknown. This study aimed to identify predictors for chronic neck and low back pain in a cohort of office workers.MethodsA prospective study was carried out among 669 healthy office workers. At baseline, risk factors were assessed using a questionnaire and standardized physical examination. A symptomatic case was defined as an individual who reported pain greater than 30 mm on a 100‐mm VAS, and chronic pain was defined as experiencing ongoing neck or low back pain for greater than 3 months over the past 6 months. Two regression models were built to analyze the risk factors for developing chronic neck and low back pain.ResultsOf the sample, 17 and 27% of office workers who reported a new onset of neck or low back pain developed chronicity, respectively. Predictors for chronic neck pain were high body mass index, frequent neck extension during the work day, high initial pain intensity, and high psychological job demands. The development of chronic low back pain was associated with history of low back pain and high initial pain intensity.ConclusionsThe findings suggest that predictors for chronic musculoskeletal pain in a subpopulation may be a subset of predictors identified in a general population or occupation specific. Successful management to prevent chronic musculoskeletal pain may also need to consider the patient's occupation.
β-lactamases encoded by blaCTX-M group I genes as determinants of resistance of ESBL-positive enterobacteriaceae in European soldiers in tropical Mali
Authors: Hagen Ralf Matthias , Hinz Hagen , Frickmann Hagen 
Published: October 2015

ESBL (extended-spectrum-β-lactamase)-positive Enterobacteriaceae, which colonized European soldiers in tropical Western African Mali, were subjected to a molecular assessment of their resistance determinants. By doing so, a better insight into the locally endemic pattern of ESBL-associated β-lactamase genes was aspired.
From a previous study on diarrhea in European soldiers on deployment in tropical Mali, 15 ESBL-positive Escherichia coli with demonstrated high clonal diversity and one positive Klebsiella pneumoniae were assessed. Polymerase chain reactions (PCRs) for blaTEM and blaSHV β-lactamase genes with subsequent sequencing for the discrimination of ESBL- and non-ESBL variants were performed, followed by four group-specific PCRs for blaCTX-M genes.
Non-ESBL-associated blaTEM-1 was identified in six out of 15 (40%) E. coli strains, while 100% of the assessed strains were positive for group I blaCTX-M.
Considering the known clonal diversity of the assessed strains, the striking restriction to one group of blaCTX-M genes accounting for the ESBL phenotypes of the isolates suggests little genetic exchange in the local setting. Under such circumstances of restricted numbers of locally endemic target genes, PCR-based screening approaches for ESBL colonization might be promising.
Explorando la distinción política interna - política internacional: un estado del arte de la discusión
Authors: Jiménez Peña Gabriel 
Published: October 2015

Para algunos teóricos la conducta de los Estados está determinada principalmente por sus características internas. En contraposición, otros argumentan que el comportamiento estatal está moldeado por el lugar que ocupan estos en el sistema internacional. El propósito aquí es abordar esta discusión y elaborar un estado del arte sobre esta distinción en las Relaciones Internacionales como ciencia. Dado que el cuerpo literario que explora la interacción política interna-política internacional es muy vasto, para abordarla o reconstruirla generalmente se acude a supuestos o lugares comunes, cinco de los cuales serán problematizados en este artículo, buscando mostrar cómo se producen de acuerdo con los desarrollos teóricos que se han construido en los últimos años sobre esta distinción.
The costs and effectiveness of chemical defenses in herbivorous insects: a meta‐analysis
Authors: Zvereva Elena L. , Kozlov Mikhail V. 
Published: October 2015

Abstract
The evolution of defensive traits and strategies depends on the intensity of selection imposed by natural enemies and on the fitness costs of defenses against these enemies. We tested several hypotheses about the evolution of chemical defenses in plant‐feeding insects using a meta‐analysis. We analyzed the effectiveness (in terms of prey survival; 159 publications) and costs (in terms of reduction in performance due to defense production; 33 publications) of chemical defenses in various prey–predator systems (140 herbivore species and 124 enemy species). The chemical defenses of insect herbivores, on average, were effective against generalist predators, were not effective against specialist predators and generalist parasitoids, and increased the risk of parasitism by specialist parasitoids. The defenses were more effective against vertebrate than against invertebrate predators and most effective against birds. Defensive compounds synthesized de novo and derived from the herbivore's food plants did not differ in the magnitude of their effects. Externalization of chemical defenses enhanced their effects on naïve vertebrate predators but simultaneously increased the risk of parasitism. The defenses of specialist herbivores were more effective than those of generalists, mostly due to species that sequestered plant allelochemicals for their own defenses. Advertising of chemical defenses by warning display enhanced their effectiveness only against vertebrate predators. Aposematic colors and patterns were more effective warning signals than other types of conspicuous coloration against both experienced and naïve vertebrate predators, suggesting that certain colors and/or patterns were more important than conspicuousness for both learning and innate avoidance. The meta‐analysis did not reveal physiological costs of the production of chemical defenses across 22 herbivore species, although the results varied strongly with the method used to measure these costs. We conclude that the cost–benefit trade‐offs driving the evolution of chemical defenses in herbivorous insects are affected by ecological costs (i.e., increased susceptibility to parasitoids) more than by costs in terms of resources. Still, a favorable cost–benefit ratio, i.e., great effects for a small expenditure, may partly explain the prevalence of chemical anti‐predator defenses in insects.
Plant–soil feedback in East‐African savanna trees
Authors: Rutten Gemma , Prati Daniel , Hemp Andreas , Fischer Markus 
Published: October 2015

AbstractResearch in savannas has focused on tree–grass interactions, whereas tree species coexistence received little attention. A leading hypothesis to explain tree coexistence is the Janzen‐Connell model, which proposes an accumulation of host‐specific enemies, e.g., soil organisms. While it has been shown in several non‐savanna case studies that seedlings dispersed away from the mother perform better than seedlings that stay close (home‐away effect), few studies tested whether foreign seedling species can replace own seedlings under conspecific adults (replacement effect). Some studies additionally tested for negative effects of conspecific biota (conspecific effect) to demonstrate the accumulation of enemies. We tested these effects by reciprocally growing seedlings of four tree species on soil collected beneath adults of all species, with and without applying a soil sterilization treatment. We found negative home‐away effects suggesting that dispersal is advantageous and negative replacement effects suggesting species replacement under adults. While negative conspecific effects indicate accumulated enemies, positive heterospecific effects indicate an accumulation of mutualists rather than enemies for some species. We suggest that plant‐soil feedbacks may well contribute to tree coexistence in savannas due to both negative conspecific and positive heterospecific feedbacks.
Depressive Symptoms and Violence Exposure: Contributors to Repeat Pregnancies Among Adolescents
Authors: Anderson Cheryl A. , Pierce Lisa 
Published: October 2015

ABSTRACTDepressive symptoms and violence exposure (VE) often cooccur and have been recognized to influence childbearing; contribution to repeat pregnancy is unclear and examined in this article. This cross-sectional, descriptive, study screened for depressive symptoms and VE among 193 adolescent mothers at a large county hospital in Southwestern United States. Repeat pregnancy and depressive symptoms characterized one-third and one-quarter of adolescents, respectively. Despite minimal disclosure of VE, repeat pregnancy was significantly influenced by child abuse and past traumatic life experiences. Assessments and interventions with adolescents should focus on frequency of repeat pregnancies and symptoms of depression and VE. Nurses and childbirth educators are poised to offer birth control information and education, support, and resources highlighting depression and VE to adolescents.