bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic background dominates the susceptibility to ventricular arrhythmias in a murine model of β-adrenergic stimulation
Authors: Jelinek Marisa , Wallach Charlotte , Ehmke Heimo , Schwoerer Alexander Peter 
Published: January 2018

AbstractIn cardiovascular research, several mouse strains with differing genetic backgrounds are used to investigate mechanisms leading to and sustaining ventricular arrhythmias. The genetic background has been shown to affect the studied phenotype in other research fields. Surprisingly little is known about potential strain-specific susceptibilities towards ventricular arrhythmias in vivo. Here, we hypothesized that inter-strain differences reported in the responsiveness of the β-adrenergic pathway, which is relevant for the development of arrhythmias, translate into a strain-specific vulnerability. To test this hypothesis, we characterized responses to β-adrenergic blockade (metoprolol) and β-adrenergic stimulation (isoproterenol) in 4 mouse strains commonly employed in cardiovascular research (Balb/c, BS, C57Bl/6 and FVB) using telemetric ECG recordings. We report pronounced differences in the electrical vulnerability following isoproterenol: Balb/c mice developed the highest number and the most complex arrhythmias while BS mice were protected. Balb/c mice, therefore, seem to be the background of choice for experiments requiring the occurrence of arrhythmias while BS mice may give insight into electrical stability. Arrhythmias did not correlate with the basal β-adrenergic tone, with the response to β-adrenergic stimulation or with the absolute heart rates during β-adrenergic stimulation. Thus, genetic factors dominate the susceptibility to ventricular arrhythmias in this model of β-adrenergic stimulation.
Targeted plasma proteomics identifies a novel, robust association between cornulin and Swedish moist snuff
Authors: Sundkvist Anneli , Myte Robin , Bodén Stina , Enroth Stefan , Gyllensten Ulf , Harlid Sophia , van Guelpen Bethany 
Published: January 2018

AbstractLifestyle behaviors are believed to influence the body’s inflammatory state. Chronic low-grade inflammation contributes to the development of major non-communicable diseases such as diabetes, cardiovascular disease and cancer. Inflammation may thus be an important link between lifestyle and disease. We evaluated self-reported physical activity, tobacco use and alcohol consumption in relation to plasma levels of 160 validated inflammatory and cancer biomarkers. The study included 138 participants from a population-based cohort, all with repeated sampling of plasma and data ten years apart, allowing consideration of both intra- and inter-individual variation. Of 17 relationships identified, the strongest was an independent, positive association between cornulin (CRNN) and Swedish moist snuff (snus) use. We replicated the finding in a second cohort of 501 individuals, in which a dose-response relationship was also observed. Snus explained approximately one fifth of the variance in CRNN levels in both sample sets (18% and 23%). In conclusion, we identified a novel, independent, dose-dependent association between CRNN and snus use. Further study is warranted, to evaluate the performance of CRNN as a potential snus biomarker. The putative importance of lifestyle behaviors on a wide range of protein biomarkers illustrates the need for more personalized biomarker cut-offs.
The peroxisome biogenesis factors posttranslationally target reticulon homology domain-containing proteins to the endoplasmic reticulum membrane
Authors: Yamamoto Yasunori , Sakisaka Toshiaki 
Published: January 2018

AbstractThe endoplasmic reticulum (ER) is shaped by a class of membrane proteins containing reticulon homology domain (RHD), the conserved hydrophobic domain encompassing two short hairpin transmembrane domains. RHD resides in the outer leaflet of the ER membrane, generating high-curvature ER membrane. While most of the membrane proteins destined to enter the secretory pathway are cotranslationally targeted and inserted into ER membrane, the molecular mechanism how the RHD-containing proteins are targeted and inserted into the ER membrane remains to be clarified. Here we show that RHD-containing proteins can be posttranslationally targeted to the ER membrane. PEX19, a cytosolic peroxin, selectively recognizes the nascent RHD-containing proteins and mediates their posttranslational targeting in cooperation with PEX3, a membrane peroxin. Thus, these peroxisome biogenesis factors provide an alternative posttranslational route for membrane insertion of the RHD-containing proteins, implying that ER membrane shaping and peroxisome biogenesis may be coordinated by the posttranslational membrane insertion.
Extra-Mediterranean glacial refugia in a Mediterranean faunal element: the phylogeography of the chalk-hill blue Polyommatus coridon (Lepidoptera, Lycaenidae)
Authors: Kühne Gero , Kosuch Joachim , Hochkirch Axel , Schmitt Thomas 
Published: January 2018

AbstractMost warm-adapted Central European species are thought to have survived ice ages exclusively in Mediterranean refugia. During recent years, this point of view has been questioned. Therefore, we tested the hypothesis that extra-Mediterranean refugia also played a role in warm-adapted insect species and selected the chalk-hill blue,Polyommatus coridon. We sequenced two mitochondrial loci (COI, CR) in 150 individuals from 30 populations covering nearly the complete range. Minimum spanning networks and other statistical analyses concordantly revealed four genetic lineages with strong phylogeographic signal: a western group in Italy, France and western/central Germany, an eastern lineage in the Balkan Peninsula, the Carpathian Basin and eastern Central Europe, an Alpine group with populations in the Alps and southern Germany and a Pyrenean group. Our results are generally consistent with previous analyses forP. coridonbased on allozymes and DNA sequences, but provide additional insights. We propose that these four lineages have evolved during allopatry in different glacial refugia, two in typical Mediterranean refugia (Apennines and Balkan Peninsulas), but two in extra-Mediterranean areas south of the Alps and Pyrenees. This supports survival of warm-adapted organisms in these regions in close geographic proximity to the refugia of high mountain species.
Self-Stigma and Age-Related Hearing Loss: A Qualitative Study of Stigma Formation and Dimensions
Authors: David Dana , Zoizner Gil , Werner Perla 
Published: January 2018

Purpose
This study explored experiences of self-stigma among older persons with age-related hearing loss (ARHL) using Corrigan's conceptualization of self-stigma process formation and the attribution model as its theoretical framework.

Method
In-depth semistructured interviews were conducted with 11 older persons (mean age = 81 years) with ARHL.

Results
Self-stigma was present in the lives of the participants. Analysis revealed the existence of 3 stages of self-stigma in which the 3 core dimensions of stigma (cognitive attributions: being old, stupid, and crippled; emotional reactions: shame, pity, and feeling ridiculed; and behavioral reactions: concealment, distancing, and adapting to hearing aids) were observed. Hearing devices emerged as having a significant influence on stigmatic experiences in all stages and dimensions of self-stigma.

Conclusion
The study contributes to the theoretical and practical understanding of self-stigma regarding ARHL as well as to the understanding of the role of hearing devices in the development of this stigma.
A near-infrared, optical, and ultraviolet polarimetric and timing investigation of complex equatorial dusty structures
Authors: Marin F. , Rojas Lobos P. A. , Hameury J. M. , Goosmann R. W. 
Published: January 2018

Context. From stars to active galactic nuclei, many astrophysical systems are surrounded by an equatorial distribution of dusty material that is, in a number of cases, spatially unresolved even with cutting edge facilities.
Aims. In this paper, we investigate if and how one can determine the unresolved and heterogeneous morphology of dust distribution around a central bright source using time-resolved polarimetric observations.
Methods. We used polarized radiative transfer simulations to study a sample of circumnuclear dusty morphologies. We explored a grid of geometrically variable models that are uniform, fragmented, and density stratified in the near-infrared, optical, and ultraviolet bands, and we present their distinctive time-dependent polarimetric signatures.
Results. As expected, varying the structure of the obscuring equatorial disk has a deep impact on the inclination-dependent flux, polarization degree and angle, and time lags we observe. We find that stratified media are distinguishable by time-resolved polarimetric observations, and that the expected polarization is much higher in the infrared band than in the ultraviolet. However, because of the physical scales imposed by dust sublimation, the average time lags of months to years between the total and polarized fluxes are important; these time lags lengthens the observational campaigns necessary to break more sophisticated, and therefore also more degenerated, models. In the ultraviolet band, time lags are slightly shorter than in the infrared or optical bands, and, coupled to lower diluting starlight fluxes, time-resolved polarimetry in the UV appears more promising for future campaigns.
Conclusions. Equatorial dusty disks differ in terms of inclination-dependent photometric, polarimetric, and timing observables, but only the coupling of these different markers can lead to inclination-independent constraints on the unresolved structures. Even though it is complex and time consuming, polarized reverberation mapping in the ultraviolet-blue band is probably the best technique to rely on in this field.
Sexual Dysfunction in Unmedicated Patients with Schizophrenia and in Healthy Controls
Authors: Dembler-Stamm Theresa , Fiebig Jana , Heinz Andreas , Gallinat Jürgen 
Published: January 2018

Abstract
Introduction Sexual dysfunction figures prominently in patients with schizophrenia; however, medication effects may play a role. The objective of this case control study was to assess differences in the presence of sexual dysfunction in unmedicated patients with schizophrenia versus healthy controls.
Methods Sexual dysfunction was assessed using the Derogatis Inventory for Sexual Function self-rating in a cross-sectional design controlling for age and gender effects. A brief sexual anamnesis was applied to describe the psychosocial background of the mostly male sample further.
Results Results show a significant difference with patients reporting more problems in most domains and with a significant correlation between severity of psychosis (Positive and Negative Syndrome Scale total scores) and the impairment of orgasm experience. The study revealed reduced sexual activities and less pleasure during sexual activities of patients.
Discussion This study implies that schizophrenia has an impact on the presence of sexual dysfunction and that sexual dysfunction is partly independent of antipsychotic treatment. Since the sample consisted mostly of first-episode males, conclusions might only be valid for this subgroup.
Hippocampal expression of a virus-derived protein impairs memory in mice
Authors: Bétourné Alexandre , Szelechowski Marion , Thouard Anne , Abrial Erika , Jean Arnaud , Zaidi Falek , Foret Charlotte , Bonnaud Emilie M. , Charlier Caroline M. , Suberbielle Elsa , Malnou Cécile E. , Granon Sylvie , Rampon Claire , Gonzalez-Dunia Daniel 
Published: January 2018

Significance
As obligate parasites, viruses have evolved strategies to hijack cellular pathways and persist in their host, sometimes without causing overt diseases. As such, they represent unique tools to decipher cellular functions and their consequences on host physiology. Here, we exploited the natural property of a virus-encoded protein known to act as a decoy substrate for protein kinase C (PKC), a pathway thought to play key roles in learning and memory processes. When selectively expressed in the hippocampal dentate gyrus of mice, this protein caused behavioral abnormalities, notably increased anxiety and impaired memory, mostly by interfering with PKC-dependent phosphorylation. Our findings provide further insight into the role of the PKC pathway in controlling cognitive functions.
Landau–Ginzburg theory of cortex dynamics: Scale-free avalanches emerge at the edge of synchronization
Authors: di Santo Serena , Villegas Pablo , Burioni Raffaella , Muñoz Miguel A. 
Published: January 2018

SignificanceThe human cortex operates in a state of restless activity, the meaning and functionality of which are still not understood. A fascinating, though controversial, hypothesis, partially backed by empirical evidence, suggests that the cortex might work at the edge of a phase transition, from which important functional advantages stem. However, the nature of such a transition remains elusive. Here, we adopt ideas from the physics of phase transitions to construct a general (Landau–Ginzburg) theory of cortical networks, allowing us to analyze their possible collective phases and phase transitions. We conclude that the empirically reported scale-invariant avalanches can possibly come about if the cortex operated at the edge of a synchronization phase transition, at which neuronal avalanches and incipient oscillations coexist.
Superresolution imaging of individual replication forks reveals unexpected prodrug resistance mechanism
Authors: Triemer Therese , Messikommer Alessandra , Glasauer Stella M. K. , Alzeer Jawad , Paulisch Miriam H. , Luedtke Nathan W. 
Published: January 2018

Significance
The pharmacophore of a clinically important prodrug, cytarabine (ara-C), was directly modified with an azide group that had little or no impact on its potency or mode of action. This “clickable” anticancer drug mimic unexpectedly revealed that the efficient incorporation of ara-C into DNA was associated with drug resistance rather than drug sensitivity. Our results therefore challenge a long-standing perception regarding the cell-type selectivity of nucleoside-based drugs. The mediators of ara-C resistance, DNA replication foci, were characterized using superresolution microscopy. In addition to providing detailed glimpses of individual replication forks in cells, these results suggest that new theranostic candidates for blood-cell analysis can be generated by introducing a bioorthogonal functional group directly into the pharmacophore of a Food and Drug Administration-approved drug.
Stimulus generalization as a mechanism for learning to trust
Authors: FeldmanHall Oriel , Dunsmoor Joseph E. , Tompary Alexa , Hunter Lindsay E. , Todorov Alexander , Phelps Elizabeth A. 
Published: January 2018

Significance
Humans can learn to trust through direct social experiences. In our everyday lives, however, we constantly meet new people where judgments of trustworthiness are blind to reputation. In these cases, what drives decisions to trust? We find a simple learning mechanism observed across species—stimulus generalization—is deployed in complex social learning environments: Individuals distrust strangers who implicitly resemble those known to be untrustworthy. These behavioral findings were mirrored at the neural level, revealing that the amygdala and caudate selectively encode the transfer of social value during moral learning. The results demonstrate a mechanism that draws on prior learning to reduce the uncertainty associated with strangers, ultimately facilitating potentially adaptive decisions to trust, or withhold trust from, unfamiliar others.
Triangular cyclic rotaxanes: Size, fluctuations, and switching properties
Authors: Reddy Prithvi , Sevick Edith M. , Williams David R. M. 
Published: January 2018

Significance
Among the most important advances in chemistry in the last 60 y is the synthesis of molecules featuring a mechanical bond, i.e., the mechanical interlocking of components. As demonstrated in linear rotaxane switches, the relative positions and orientations among interlocked components can be altered to produce molecular-scale changes in size and shape. Here, we describe the conformations of a simple molecule made cyclic with mechanical bonding. Although the molecule, a cyclic [3]rotaxane, forms a cycle that is always a triangle and hence planar, we show that with only three mechanical degrees of freedom, characteristics such as interior cycle area, perimeter, and inscribed radius fluctuate significantly. Our model, based on statistical mechanics, suggests that the cyclic rotaxane can be used as the host in an inclusion compound, with the potential to switch sizes of the interior cycle or “pore.”
TRPV1 channels and the progesterone receptor Sig-1R interact to regulate pain
Authors: Ortíz-Rentería Miguel , Juárez-Contreras Rebeca , González-Ramírez Ricardo , Islas León D. , Sierra-Ramírez Félix , Llorente Itzel , Simon Sidney A. , Hiriart Marcia , Rosenbaum Tamara , Morales-Lázaro Sara L. 
Published: January 2018

Significance
The TRPV1 ion channel has been widely associated with the generation of painful responses. The responses of cells expressing this ion channel and, presumably, the overall pain response of an organism may be regulated by controlling the amount of TRPV1 channels in the plasma membrane. TRPV1 levels can be regulated by its interaction with intracellular proteins, but there are no studies describing TRPV1 or any other mammalian TRP channel’s association with chaperones or how these interactions may affect the perception of pain. Here, we show that TRPV1-dependent pain is decreased through Sig-1R antagonism by progesterone and determine the presence of a physical interaction between these two proteins that may reduce pain under physiological conditions such as pregnancy.
Alarm calls evoke a visual search image of a predator in birds
Authors: Suzuki Toshitaka N. 
Published: January 2018

SignificanceIn human speech, words often cause listeners to retrieve visual mental images of target objects. In nonhuman animal communication systems, many key, language-like features have been demonstrated, but there is still no evidence that animal signals evoke mental images of objects in receivers. Japanese tits produce specific alarm calls when encountering a predatory snake. Here, I show that simply hearing these calls causes tits to become more visually perceptive to objects resembling snakes (moving sticks). This result indicates that before having detected a real snake, tits retrieve its visual image from snake-specific alarm calls and uses this to search out snakes. This study provides evidence for a call-evoked visual search image in a nonhuman animal.
Lysosomal enzyme tripeptidyl peptidase 1 destabilizes fibrillar Aβ by multiple endoproteolytic cleavages within the β-sheet domain
Authors: Solé-Domènech Santiago , Rojas Ana V. , Maisuradze Gia G. , Scheraga Harold A. , Lobel Peter , Maxfield Frederick R. 
Published: January 2018

Significance
Alzheimer’s disease is the leading cause of dementia. Accumulation of amyloid-beta (Aβ) plaques, which include β-sheet fibrils of Aβ, is a hallmark of the disease. Aβ aggregates can be endocytosed by microglia and delivered to lysosomes, but degradation of fibrillar Aβ in microglial lysosomes is slow. Identification of novel enzymes that proteolyze fibrillar Aβ will lead to improved understanding of fibrillar Aβ degradation, which may lead to new therapeutic approaches. In this study, we demonstrate that tripeptidyl peptidase 1 (TPP1), a lysosomal serine protease, is able to proteolyze fibrillar Aβ efficiently, which is a novel role for TPP1 in the degradation of fibrillar Aβ that might lead to new approaches to enhance Aβ degradation.
Different situations, similar outcomes
Authors: Putnam Michael T. , Kupisch Tanja , Pascual y Cabo Diego 
Published: January 2018

Abstract
The rise of scientific inquiry focusing on bilingualism over the past few decades has also borne witness to an increase in the study of individuals and communities who speak a native language that is not the sociolinguistically dominant language of the environment in which they grew up. While it is common practice to refer to these diverse groups and individuals as “heritage speakers”, it is unclear whether it is appropriate to classify all of them under the same terminology. In this chapter, we take a closer look at three different groups: (i) children, (ii) young adults, and (iii) elderly, moribund bilinguals who have all been referred to as heritage speakers in the literature. After exploring aspects of phonological, (morpho)syntactic, and semantic/pragmatic developments, we show that a great deal of symmetry exists between them, thus justifying the cohesive, overarching label of “heritage speakers” to all three sub-groups. Finally, we outline what this broader definition of heritage speakers means for long-standing debates in the literature, such as those that concern the acquisition, development, and maintenance of the heritage grammar across the lifespan.
Words on the brain
Authors: Bobb Susan C. , Kroll Judith F. 
Published: January 2018

Abstract
In this chapter, we view the recent evidence on the bilingual lexicon that points to a dynamic view of lexical processes. In contrast to earlier assumptions that words in the bilingual’s two languages were represented and processed independently, the findings of studies with both adults and children demonstrate that words in both languages are activated in parallel. Critically, the co-activation of the two languages does not depend on their structural similarity but on the very presence of the two languages themselves. The consequences of cross-language activation can be seen in language processing, not only from the first language (L1) to the second (L2) but also from the L2 to the L1. They can also be seen in the recruitment of cognitive resources in response to the demands of language processing and in the way that words come to influence language processes at the level of the grammar. From this perspective, the lexicon is far more than a collection of words but a lens into the dynamics of bilingualism.
Bilingualism and children with developmental language and communication disorders
Authors: Paradis Johanne , Govindarajan Krithika 
Published: January 2018

Abstract
Research on bilingualism in children with developmental language and communication disorders has focused primarily on children with specific language impairment (SLI), but some recent research has emerged on children with Autism Spectrum Disorder (ASD). In this chapter we review research on bilingual development in children with SLI and ASD organized around the following topics: (1) The capacity for successful bilingualism in children with developmental disorders; (2) The linguistic profiles of bilinguals with SLI across different languages and linguistic subdomains; (3) Crosslinguistic influence in bilingual development with SLI; (4) Development of a minority/heritage language in children with developmental disorders, and (6) Challenges and strategies in assessment and intervention practices with bilingual children.