julilili42/papers huggingface dataset:
Regulation of the Voltage Gated K<sup>+</sup> Channel K<sub>v1.3</sub> by Recombinant Human Klotho Protein
2014-01-01

&lt;b&gt;&lt;i&gt;Background/Aims: &lt;/i&gt;&lt;/b&gt;Klotho, a protein mainly produced in the kidney and released into circulating blood, contributes to the negative regulation of 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D&lt;sub&gt;3&lt;/sub&gt; formation and is thus a powerful regulator of mineral metabolism. As β-glucuronidase, alpha Klotho protein further regulates the stability of several carriers and channels in the plasma membrane and thus regulates channel and transporter activity. Accordingly, alpha Klotho protein participates in the regulation of diverse functions seemingly unrelated to mineral metabolism including lymphocyte function. The present study explored the impact of alpha Klotho protein on the voltage gated K&lt;sup&gt;+&lt;/sup&gt; channel K&lt;sub&gt;v1.3&lt;/sub&gt;. &lt;b&gt;&lt;i&gt;Methods: &lt;/i&gt;&lt;/b&gt;cRNA encoding K&lt;sub&gt;v1.3&lt;/sub&gt; (KCNA3) was injected into &lt;i&gt;Xenopus&lt;/i&gt; oocytes and depolarization induced outward current in K&lt;sub&gt;v1.3&lt;/sub&gt; expressing &lt;i&gt;Xenopus&lt;/i&gt; oocytes determined utilizing dual electrode voltage clamp. Experiments were performed without or with prior treatment with recombinant human Klotho protein (50 ng/ml, 24 hours) in the absence or presence of a β-glucuronidase inhibitor D-saccharic acid-1,4-lactone (DSAL, 10 μM). Moreover, the voltage gated K&lt;sup&gt;+&lt;/sup&gt; current was determined in Jcam lymphoma cells by whole cell patch clamp following 24 hours incubation without or with recombinant human Klotho protein (50 ng/ml, 24 hours). K&lt;sub&gt;v1.3&lt;/sub&gt; protein abundance in Jcam cells was determined utilising fluorescent antibodies in flow cytometry. &lt;b&gt;&lt;i&gt;Results: &lt;/i&gt;&lt;/b&gt;In K&lt;sub&gt;v1.3&lt;/sub&gt; expressing &lt;i&gt;Xenopus&lt;/i&gt; oocytes the K&lt;sub&gt;v1.3&lt;/sub&gt; currents and the protein abundance of K&lt;sub&gt;v1.3&lt;/sub&gt; were both significantly enhanced after treatment with recombinant human Klotho protein (50 ng/ml, 24 hours), an effect reversed by presence of DSAL. Moreover, treatment with recombinant human Klotho protein increased K&lt;sub&gt;v&lt;/sub&gt; currents and K&lt;sub&gt;v1.3&lt;/sub&gt; protein abundance in Jcam cells. &lt;b&gt;&lt;i&gt;Conclusion: &lt;/i&gt;&lt;/b&gt;Alpha Klotho protein enhances K&lt;sub&gt;v1.3&lt;/sub&gt; channel abundance and K&lt;sub&gt;v1.3&lt;/sub&gt; currents in the plasma membrane, an effect depending on its β-glucuronidase activity.
Grounded Theory
2014-01-01

Wenig wurde bislang Ã1⁄4ber die erkenntnistheoretische Fundierung der Grounded Theory in der pragmatischen Sozialphilosophie und die daraus resultierenden Konsequenzen fÃ1⁄4r das VerstÃ¤ndnis der methodologischen Konzeption wie der praktischen Verfahren geschrieben. Der Band schlieÃt diese LÃ1⁄4cke, indem das Erkenntnismodell, ausgehend von den Arbeiten von C.S. Peirce, J. Dewey, G.H. Mead und W. James, vorgestellt und den Spuren nachgegangen wird, die dieses Modell als GeltungsbegrÃ1⁄4ndung in der Methodologie der Grounded Theory hinterlassen hat. Dabei geht der Text auch auf die gravierenden methodologischen Unterschiede zwischen der von Anselm L. Strauss geprÃ¤gten und der von Barney G. Glaser vertretenen Variante von Grounded Theory ein und beschÃ¤ftigt sich mit wesentlichen Weiterentwicklungen einer pragmatistischen Grounded Theory im Kontext postmodernen Denkens. Â Der Inhalt Was ist (eine gute) Grounded Theory? â¢ Erkenntnismodell und Wirklichkeitsbegriff im Pragmatismus â¢ Theoriebegriff, Vorwissen und das Problem der Induktion â¢ Glasers Angriff auf Strauss und Corbin als Ausdruck fundamentaler sozialtheoretischer und erkenntnislogischer Differenzen â¢ Grounded Theory und Situationsanalyse: Zur Weiterentwicklung der Grounded Theory Â Die Zielgruppen Praktiker, Studierende und Lehrende auf dem Fachgebiet der Sozialwissenschaften und der qualitativ-interpretativen Sozialforschung Â Der Autor Prof. Dr. JÃ¶rg StrÃ1⁄4bing lehrt Soziologie und qualitative Methoden an der Eberhard Karls UniversitÃ¤t TÃ1⁄4bingen.
Intestinal barrier in inflammatory bowel disease
2014-01-01

A complex mucosal barrier protects as the first line of defense the surface of the healthy intestinal tract from adhesion and invasion by luminal microorganisms. In this review, we provide an overview about the major components of this protective system as for example an intact epithelium, the synthesis of various antimicrobial peptides (AMPs) and the formation of the mucus layer. We highlight the crucial importance of their correct functioning for the maintenance of a proper intestinal function and the prevention of dysbiosis and disease. Barrier disturbances including a defective production of AMPs, alterations in thickness or composition of the intestinal mucus layer, alterations of pattern-recognition receptors, defects in the process of autophagy as well as unresolved endoplasmic reticulum stress result in an inadequate host protection and are thought to play a crucial role in the pathogenesis of the inflammatory bowel diseases Crohn's disease and ulcerative colitis.
The Myth of Cognitive Decline: Non‐Linear Dynamics of Lifelong Learning
2014-01-01

Abstract As adults age, their performance on many psychometric tests changes systematically, a finding that is widely taken to reveal that cognitive information‐processing capacities decline across adulthood. Contrary to this, we suggest that older adults' changing performance reflects memory search demands, which escalate as experience grows. A series of simulations show how the performance patterns observed across adulthood emerge naturally in learning models as they acquire knowledge. The simulations correctly identify greater variation in the cognitive performance of older adults, and successfully predict that older adults will show greater sensitivity to fine‐grained differences in the properties of test stimuli than younger adults. Our results indicate that older adults' performance on cognitive tests reflects the predictable consequences of learning on information‐processing, and not cognitive decline. We consider the implications of this for our scientific and cultural understanding of aging.
Fungal allergy in asthma–state of the art and research needs
2014-01-01

Abstract Sensitization to fungi and long term or uncontrolled fungal infection are associated with poor control of asthma, the likelihood of more severe disease and complications such as bronchiectasis and chronic pulmonary aspergillosis. Modelling suggests that &gt;6.5 million people have severe asthma with fungal sensitizations (SAFS), up to 50% of adult asthmatics attending secondary care have fungal sensitization, and an estimated 4.8 million adults have allergic bronchopulmonary aspergillosis (ABPA). There is much uncertainty about which fungi and fungal allergens are relevant to asthma, the natural history of sensitisation to fungi, if there is an exposure response relationship for fungal allergy, and the pathogenesis and frequency of exacerbations and complications. Genetic associations have been described but only weakly linked to phenotypes. The evidence base for most management strategies in ABPA, SAFS and related conditions is weak. Yet straightforward clinical practice guidelines for management are required. The role of environmental monitoring and optimal means of controlling disease to prevent disability and complications are not yet clear. In this paper we set out the key evidence supporting the role of fungal exposure, sensitisation and infection in asthmatics, what is understood about pathogenesis and natural history and identify the numerous areas for research studies.
Glacier mass changes on the Tibetan Plateau 2003–2009 derived from ICESat laser altimetry measurements
2014-01-01

Glacier mass changes are a valuable indicator of climate variability and monsoon oscillation on the underexplored Tibetan Plateau. In this study data from the Ice Cloud and Elevation Satellite (ICESat) is employed to estimate elevation and mass changes of glaciers on the Tibetan Plateau between 2003 and 2009. In order to get a representative sample size of ICESat measurements, glaciers on the Tibetan Plateau were grouped into eight climatically homogeneous sub-regions. Most negative mass budgets of − 0.77 ± 0.35 m w.e. a ^−1 were found for the Qilian Mountains and eastern Kunlun Mountains while a mass gain of + 0.37 ± 0.25 m w.e. a ^−1 was found in the westerly-dominated north-central part of the Tibetan Plateau. A total annual mass budget of − 15.6 ± 10.1 Gt a ^−1 was estimated for the eight sub-regions sufficiently covered by ICESat data which represents ∼80% of the glacier area on the Tibetan Plateau. 13.9 ± 8.9 Gt a ^−1 (or 0.04 ± 0.02 mm a ^−1 sea-level equivalent) of the total mass budget contributed ‘directly’ to the global sea-level rise while 1.7 ± 1.9 Gt a ^−1 drained into endorheic basins on the plateau.
A Comparative View on Human Somatic Cell Sources for iPSC Generation
2014-01-01

The breakthrough of reprogramming human somatic cells was achieved in 2006 by the work of Yamanaka and Takahashi. From this point, fibroblasts are the most commonly used primary somatic cell type for the generation of induced pluripotent stem cells (iPSCs). Various characteristics of fibroblasts supported their utilization for the groundbreaking experiments of iPSC generation. One major advantage is the high availability of fibroblasts which can be easily isolated from skin biopsies. Furthermore, their cultivation, propagation, and cryoconservation properties are uncomplicated with respect to nutritional requirements and viability in culture. However, the required skin biopsy remains an invasive approach, representing a major drawback for using fibroblasts as the starting material. More and more studies appeared over the last years, describing the reprogramming of other human somatic cell types. Cells isolated from blood samples or urine, as well as more unexpected cell types, like pancreatic islet beta cells, synovial cells, or mesenchymal stromal cells from wisdom teeth, show promising characteristics for a reprogramming strategy. Here, we want to highlight the advantages of keratinocytes from human plucked hair as a widely usable, noninvasive harvesting method for primary material in comparison with other commonly used cell types.
Testing theories of irony processing using eye-tracking and ERPs.
2014-01-01

Not much is known about how people comprehend ironic utterances, and to date, most studies have simply compared processing of ironic versus non-ironic statements. A key aspect of the graded salience hypothesis, distinguishing it from other accounts (such as the standard pragmatic view and direct access view), is that it predicts differences between processing of familiar and unfamiliar ironies. Specifically, if an ironic utterance is familiar, then the ironic interpretation should be available without the need for extra inferential processes, whereas for unfamiliar ironies, the literal interpretation would be computed first, and a mismatch with context would lead to a re-interpretation of the statement as being ironic. We recorded participants’ eye movements while they were reading (Experiment 1), and electrical brain activity while they were listening to (Experiment 2), familiar and unfamiliar ironies compared to non-ironic controls. Results show disruption to eye movements and an N400-like effect for unfamiliar ironies only, supporting the predictions of the graded salience hypothesis. In addition, in Experiment 2, a late positivity was found for both familiar and unfamiliar ironic materials, compared to non-ironic controls. We interpret this positivity as reflecting ongoing conflict between the literal and ironic interpretations of the utterance. (PsycINFO Database Record (c) 2016 APA, all rights reserved)
On the Immunological Theory of Aging
2014-01-01

Aging is a complex phenomenon the cause of which is not fully understood, despite the plethora of theories proposed to explain it. As we age, changes in essentially all physiological functions, including immunity, are apparent. Immune responses decrease with aging, contributing to the increased incidence of different chronic diseases with an inflammatory component (sometimes referred to as 'inflamm-aging'). It is clear from many studies that human longevity may be influenced by these changes in the immune system, but how they proceed is not clearly determined. In this chapter, we will review the age-related changes in the immune response and assess the validity of the immune theory of aging (i.e. that these changes in immune response are the primary cause of aging). Many data in humans support the notion that age-associated immune dysfunction may at least in part explain the aging process. Explanatory power may be enhanced by combination with other theories such as the free radical theory. More longitudinal studies are needed to corroborate the immune theory of aging.
Intranasal Delivery of Bone Marrow-Derived Mesenchymal Stem Cells, Macrophages, and Microglia to the Brain in Mouse Models of Alzheimer's and Parkinson's Disease
2014-01-01

In view of the rapid preclinical development of cell-based therapies for neurodegenerative disorders, traumatic brain injury, and tumors, the safe and efficient delivery and targeting of therapeutic cells to the central nervous system is critical for maintaining therapeutic efficacy and safety in the respective disease models. Our previous data demonstrated therapeutically efficacious and targeted delivery of mesenchymal stem cells (MSCs) to the brain in the rat 6-hydroxydopamine model of Parkinson's disease (PD). The present study examined delivery of bone marrow-derived MSCs, macrophages, and microglia to the brain in a transgenic model of PD [(Thy1)-h[A30P] aS] and an APP/PS1 model of Alzheimer's disease (AD) via intranasal application (INA). INA of microglia in naive BL/6 mice led to targeted and effective delivery of cells to the brain. Quantitative PCR analysis of eGFP DNA showed that the brain contained the highest amount of eGFP-microglia (up to 2.1 × 10 4 ) after INA of 1 × 10 6 cells, while the total amount of cells detected in peripheral organs did not exceed 3.4 × 10 3 . Seven days after INA, MSCs expressing eGFP were detected in the olfactory bulb (OB), cortex, amygdala, striatum, hippocampus, cerebellum, and brainstem of (Thy1)-h[A30P] aS transgenic mice, showing predominant distribution within the OB and brainstem. INA of eGFP-expressing macrophages in 13-month-old APP/PS1 mice led to delivery of cells to the OB, hippocampus, cortex, and cerebellum. Both MSCs and macrophages contained Iba-1-positive population of small microglia-like cells and Iba-1-negative large rounded cells showing either intracellular amyloid β (macrophages in APP/PS1 model) or α-synuclein [MSCs in (Thy1)-h[A30P] aS model] immunoreactivity. Here, we show, for the first time, intranasal delivery of cells to the brain of transgenic PD and AD mouse models. Additional work is needed to determine the optimal dosage (single treatment regimen or repeated administrations) to achieve functional improvement in these mouse models with intranasal microglia/macrophages and MSCs. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.
Changes in situation models modulate processes of event perception in audiovisual narratives.
2014-01-01

Humans understand text and film by mentally representing their contents in situation models. These describe situations using dimensions like time, location, protagonist, and action. Changes in 1 or more dimensions (e.g., a new character enters the scene) cause discontinuities in the story line and are often perceived as boundaries between 2 meaningful units. Recent theoretical advances in event perception led to the assumption that situation models are represented in the form of event models in working memory. These event models are updated at event boundaries. Points in time at which event models are updated are important: Compared with situations during an ongoing event, situations at event boundaries are remembered more precisely and predictions about what happens next become less reliable. We hypothesized that these effects depend on the number of changes in the situation model. In 2 experiments, we had participants watch sitcom episodes and measured recognition memory and prediction performance for event boundaries that contained a change in 1, 2, 3, or 4 dimensions. Results showed a linear relationship: the more dimensions changed, the higher recognition performance was. At the same time, participants' predictions became less reliable with an increasing number of dimension changes. These results suggest that updating of event models at event boundaries occurs incrementally.
Tip‐enhanced Raman spectroscopy – an interlaboratory reproducibility and comparison study
2014-01-01

Since its first experimental realization, tip‐enhanced Raman spectroscopy (TERS) has emerged as a potentially powerful nanochemical analysis tool. However, questions about the comparability and reproducibility of TERS data have emerged. This interlaboratory comparison study addresses these issues by bringing together different TERS groups to perform TERS measurements on nominally identical samples. Based on the spectra obtained, the absolute and relative peak positions, number of bands, peak intensity ratios, and comparability to reference Raman and surface‐enhanced Raman spectroscopy (SERS) data are discussed. Our general findings are that all research groups obtained similar spectral patterns, irrespective of the setup or tip that was used. The TERS (and SERS) spectra consistently showed fewer bands than the conventional Raman spectrum. When comparing these three methods, the spectral pattern match and substance identification is readily possible. Absolute and relative peak positions of the three major signals of thiophenol scattered by 19 and 9 cm −1 , respectively, which can probably be attributed to different spectrometer calibrations. However, within the same group (but between different tips), the signals only scattered by 3 cm −1 on average. This study demonstrated the suitability of TERS as an analytical tool and brings TERS a big step forward to becoming a routine technique. Copyright © 2014 John Wiley &amp; Sons, Ltd.
Lexical differences between Tuscan dialects and standard Italian: Accounting for geographic and sociodemographic variation using generalized additive mixed modeling
2014-01-01

This study uses a generalized additive mixed-effects regression model to predict lexical differences in Tuscan dialects with respect to standard Italian. We used lexical information for 170 concepts used by 2,060 speakers in 213 locations in Tuscany. In our model, geographical position was found to be an important predictor, with locations more distant from Florence having lexical forms more likely to differ from standard Italian. In addition, the geographical pattern varied significantly for low- versus high-frequency concepts and older versus younger speakers. Younger speakers generally used variants more likely to match the standard language. Several other factors emerged as significant. Male speakers as well as farmers were more likely to use lexical forms different from standard Italian. In contrast, higher-educated speakers used lexical forms more likely to match the standard. The model also indicates that lexical variants used in smaller communities are more likely to differ from standard Italian. The impact of community size, however, varied from concept to concept. For a majority of concepts, lexical variants used in smaller communities are more likely to differ from the standard Italian form. For a minority of concepts, however, lexical variants used in larger communities are more likely to differ from standard Italian. Similarly, the effect of the other community- and speaker-related predictors varied per concept. These results clearly show that the model succeeds in teasing apart different forces influencing the dialect landscape and helps us to shed light on the complex interaction between the standard Italian language and the Tuscan dialectal varieties. In addition, this study illustrates the potential of generalized additive mixed-effects regression modeling applied to dialect data.
Motor Training in Degenerative Spinocerebellar Disease: Ataxia-Specific Improvements by Intensive Physiotherapy and Exergames
2014-01-01

The cerebellum is essentially involved in movement control and plays a critical role in motor learning. It has remained controversial whether patients with degenerative cerebellar disease benefit from high-intensity coordinative training. Moreover, it remains unclear by which training methods and mechanisms these patients might improve their motor performance. Here, we review evidence from different high-intensity training studies in patients with degenerative spinocerebellar disease. These studies demonstrate that high-intensity coordinative training might lead to a significant benefit in patients with degenerative ataxia. This training might be based either on physiotherapy or on whole-body controlled videogames (“exergames”). The benefit shown in these studies is equal to regaining one or more years of natural disease progression. In addition, first case studies indicate that even subjects with advanced neurodegeneration might benefit from such training programs. For both types of training, the observed clinical improvements are paralleled by recoveries in ataxia-specific dysfunctions (e.g., multijoint coordination and dynamic stability). Importantly, for both types of training, the retention of the effects seems to depend on the frequency and continuity of training. Based on these studies, we here present preliminary recommendations for clinical practice, and articulate open questions that might guide future studies on neurorehabilitation in degenerative spinocerebellar disease.
Aristolochic Acid Induced Suicidal Erythrocyte Death
2014-01-01

&lt;b&gt;&lt;i&gt;Background/Aims: &lt;/i&gt;&lt;/b&gt;Aristolochic Acid, a component of &lt;i&gt;Aristolochia&lt;/i&gt; plants, has been shown to cause acute kidney injury, renal aristolochic acid nephropathy, Balkan endemic nephropathy, and urothelial carcinoma. Aristolochic acid nephropathy may be associated with severe anemia. The anemia could theoretically be due to stimulation of eryptosis, the suicidal death of erythrocytes characterized by cell shrinkage and cell membrane scrambling with translocation of phosphatidylserine to the erythrocyte cell membrane surface. Signalling involved in the stimulation of eryptosis include increase of cytosolic Ca&lt;sup&gt;2+&lt;/sup&gt;-activity ([Ca&lt;sup&gt;2+&lt;/sup&gt;]&lt;sub&gt;i&lt;/sub&gt;) and formation of ceramide. &lt;b&gt;&lt;i&gt;Methods: &lt;/i&gt;&lt;/b&gt;Cell volume was estimated from forward scatter, phosphatidylserine-exposure from annexin V binding, [Ca&lt;sup&gt;2+&lt;/sup&gt;]&lt;sub&gt;i&lt;/sub&gt; from Fluo3 fluorescence, and ceramide abundance from binding of fluorescent antibodies in flow cytometry. &lt;b&gt;&lt;i&gt;Results: &lt;/i&gt;&lt;/b&gt;A 48 hours exposure to Aristolochic Acid (&amp;#8805; 75 g/ml) was followed by a significant decrease of forward scatter and increase of annexin-V-binding. The effects were paralleled by a significant increase of [Ca&lt;sup&gt;2+&lt;/sup&gt;]&lt;sub&gt;i&lt;/sub&gt; and significantly blunted, but not abrogated by removal of extracellular Ca&lt;sup&gt;2+&lt;/sup&gt;. Aristolochic Acid further significantly increased ceramide abundance. &lt;b&gt;&lt;i&gt;Conclusions: &lt;/i&gt;&lt;/b&gt;Aristolochic Acid triggers eryptosis, an effect at least in part due to entry of extracellular Ca&lt;sup&gt;2+&lt;/sup&gt; and ceramide formation. i 2014 S. Karger AG, Basel