julilili42/papers huggingface dataset:
Inhibition of Ca2+Entry and Suicidal Erythrocyte Death by Naringin
2012-01-01

Naringin is a dietary flavonoid from citrus fruits with antioxidant and antiapoptotic activity. Similar to apoptosis of nucleated cells, suicidal death of erythrocytes or eryptosis is paralleled by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the erythrocyte surface. Eryptosis is triggered by increased cytosolic Ca(2+) activity, e.g. following energy depletion or oxidative stress. The present study thus explored whether naringin interferes with eryptosis. To this end, the cytosolic Ca(2+) concentration was estimated from Fluo3 fluorescence, phosphatidylserine exposure from annexin-V-binding and cell volume from forward scatter in FACS analysis. As a result, energy depletion (48 h glucose removal) and oxidative stress (30 min exposure to 0.3 mM tert-butylhydroperoxide) increased Fluo-3 fluorescence, decreased the erythrocyte forward scatter and enhanced the percentage of annexin-V-binding erythrocytes. Naringin (up to 40 μM) did not significantly modify Fluo-3 fluorescence, erythrocyte forward scatter or annexin-V-binding in the presence of glucose and absence of oxidative stress. Naringin, however, significantly blunted the effect of glucose depletion and oxidative stress on Fluo-3 fluorescence, erythrocyte forward scatter or annexin-V-binding. In conclusion, naringin blunts the increase of cytosolic Ca(2+) concentration, the shrinkage, the cell membrane scrambling and thus the suicidal death of erythrocytes following energy depletion or oxidative stress.
Enhanced Erythrocyte Membrane Exposure of Phosphatidylserine Following Sorafenib Treatment: Anin vivoandin vitroStudy
2012-01-01

The present observations disclose novel effects of sorafenib, i.e. stimulation of suicidal erythrocyte death or eryptosis, which may contribute to the pathogenesis of anemia in Nexavar(®)-based chemotherapy.
Tanshinone IIA Stimulates Erythrocyte Phosphatidylserine Exposure
2012-01-01

Tanshinone IIA, an antimicrobial, antioxidant, antianaphylactic, antifibrotic, vasodilating, antiatherosclerotic, organo-protective and antineoplastic component from the rhizome of Salvia miltiorrhiza, is known to trigger apoptosis of tumor cells. Tanshinone IIA is effective in part through mitochondrial depolarization and altered gene expression. Erythrocytes lack mitochondria and nuclei but may undergo eryptosis, an apoptosis-like suicidal cell death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Eryptosis is triggered by increase of cytosolic Ca(2+) activity, ATP depletion and ceramide formation. The present study explored, whether tanshinone IIA elicits eryptosis. Cytosolic Ca(2+)-concentration was determined from Fluo3-fluorescence, cell volume from forward scatter, phosphatidylserine exposure from binding of fluorescent annexin V, hemolysis from hemoglobin concentration in the supernatant, ATP concentration utilizing luciferin-luciferase and ceramide formation utilizing fluorescent anticeramide antibodies. Clearance of circulating erythrocytes was estimated by CFSE-labeling. A 48 h exposure to tanshinone IIA (≥10 μM) significantly increased cytosolic Ca(2+)-concentration, decreased ATP concentration (25 μM), increased lactate concentration (25 μM), increased ceramide formation (25 μM), decreased forward scatter, increased annexin-V-binding and increased (albeit to a much smaller extent) hemolysis. The effect of 25 μM tanshinone IIA on annexin-V binding was partially reversed in the nominal absence of Ca(2+). Labelled tanshinone IIA-treated erythrocytes were more rapidly cleared from the circulating blood in comparison to untreated erythrocytes. The present observations reveal a completely novel effect of tanshinone IIA, i.e. triggering of Ca(2+) entry, ATP depletion and ceramide formation in erythrocytes, events eventually leading to eryptosis with cell shrinkage and cell membrane scrambling.
Effect of Casein Kinase 1a Activator Pyrvinium Pamoate on Erythrocyte Ion Channels
2012-01-01

Pharmacological modification of protein kinase CK1 (casein kinase 1) has previously been shown to influence suicidal erythrocyte death or eryptosis, which is triggered by activation of Cl--sensitive Ca2+-permeable cation channels. Ca2+ entering through those channels stimulates cell membrane scrambling and opens Ca2+-activated K+-channels resulting in KCl exit and thus cell shrinkage. The specific CK1-inhibitor D4476 (1 μM) blunted, whereas the specific CK1 αactivator pyrvinium pamoate (10 μM) enhanced cell membrane scrambling. The substances were at least partially effective through modification of cytosolic Ca2+-activity. The present study explored, whether pyrvinium pamoate indeed influences Cl--sensitive cation-channels in erythrocytes. As a result, removal of Cl-increased Fluo3-fluorescence (reflecting cytosolic Ca2+-activity), triggered cell membrane scrambling (apparent from annexin-V-binding), and decreased forward scatter (pointing to cell shrinkage). Pyrvinium pamoate significantly augmented the effect of Cl--removal on Fluo3 fluorescence and annexin-V-binding, but blunted the effect on forward scatter. According to whole cell patch clamp recording, Cl-removal activated a cation current, which was significantly enhanced by pyrvinium pamoate. Pyrvinium pamoate inhibited Ca2+-activated K+-channels. Ca2+-ionophore ionomycin (1 μM) decreased forward scatter, an effect significantly blunted by pyrvinium pamoate. In conclusion, pyrvinium pamoate activates Cl--sensitive Ca2+-permeable cation channels with subsequent Ca2+-entry and inhibits Ca2+-activated K+-channels thus blunting the stimulating effect of Ca2+ on those channels, K+-exit and thus cell shrinkage.
Communicating with Cost-based Implicature: a Game-Theoretic Approach to Ambiguity
2012-01-01

A game-theoretic approach to linguistic com-munication predicts that speakers can mean-ingfully use ambiguous forms in a discourse context in which only one of several available referents has a costly unambiguous form and in which rational interlocutors share knowl-edge of production costs. If a speaker pro-duces a low-cost ambiguous form to avoid us-ing the high-cost unambiguous form, a ratio-nal listener will infer that the high-cost entity was the intended entity, or else the speaker would not have risked ambiguity. We report data from two studies in which pairs of speak-ers show alignment of their use of ambiguous forms based on this kind of shared knowledge. These results extend the analysis of cost-based pragmatic inferencing beyond that previously associated only with fixed lexical hosts. 1
Overlapping Cardiac Phenotype Associated with a Familial Mutation in the Voltage Sensor of the KCNQ1 Channel
2012-01-01

The mutation acted in a E-subunit dependent manner, suggesting I(Ks) function altered by the presence of different KCNE subunits in sinus node, atria and ventricles as the molecular basis of sinus bradycardia, fAF and LQTS in mutation carriers.
Effects of Renal Sympathetic Denervation on 24-hour Blood Pressure Variability
2012-01-01

In patients with therapy-refractory arterial hypertension, RDN leads to significant reductions of BP variability. Effects of RDN on BP variability over 24 h were more pronounced than on average levels of BP.
Coupling BCI and cortical stimulation for brain-state-dependent stimulation: methods for spectral estimation in the presence of stimulation after-effects
2012-01-01

Brain-state-dependent stimulation (BSDS) combines brain-computer interfaces (BCIs) and cortical stimulation into one paradigm that allows the online decoding for example of movement intention from brain signals while simultaneously applying stimulation. If the BCI decoding is performed by spectral features, stimulation after-effects such as artefacts and evoked activity present a challenge for a successful implementation of BSDS because they can impair the detection of targeted brain states. Therefore, efficient and robust methods are needed to minimize the influence of the stimulation-induced effects on spectral estimation without violating the real-time constraints of the BCI. In this work, we compared four methods for spectral estimation with autoregressive (AR) models in the presence of pulsed cortical stimulation. Using combined EEG-TMS (electroencephalography-transcranial magnetic stimulation) as well as combined electrocorticography (ECoG) and epidural electrical stimulation, three patients performed a motor task using a sensorimotor-rhythm BCI. Three stimulation paradigms were varied between sessions: (1) no stimulation, (2) single stimulation pulses applied independently (open-loop), or (3) coupled to the BCI output (closed-loop) such that stimulation was given only while an intention to move was detected using neural data. We found that removing the stimulation after-effects by linear interpolation can introduce a bias in the estimation of the spectral power of the sensorimotor rhythm, leading to an overestimation of decoding performance in the closed-loop setting. We propose the use of the Burg algorithm for segmented data to deal with stimulation after-effects. This work shows that the combination of BCIs controlled with spectral features and cortical stimulation in a closed-loop fashion is possible when the influence of stimulation after-effects on spectral estimation is minimized.
Inhibitory Effect of Furosemide on Non-Selective Voltage-Independent Cation Channels in Human Erythrocytes
2012-01-01

The present study shows for the first time that the loop diuretic furosemide applied at micromolar concentrations (10 - 100 μM) inhibits non-selective cation channel activity in and eryptosis of human erythrocytes.
Upregulation of Na+-coupled Glucose transporter SGLT1 by Tau Tubulin Kinase 2
2012-01-01

The Tau-tubulin-kinase 2 (TTBK2) is a serine/threonine kinase expressed in various tissues including tumors. Up-regulation of TTBK2 increases resistance of tumor cells against antiangiogenic treatment and confers cell survival. Tumor cell survival critically depends on cellular uptake of glucose, which is partially accomplished by SGLT1 (SLC5A1) mediated Na(+)-coupled glucose transport. The present study explored whether TTBK2 participates in the regulation of SGLT1 activity. To this end, electrogenic glucose transport was determined in Xenopus oocytes expressing SGLT1 with or without wild-type TTBK2, truncated TTBK2([1-450]) or kinase inactive mutants TTBK2-KD and TTBK2-KD([1-450]). TTBK2, but not TTBK2([1-450]), TTBK2-KD or TTBK2-KD([1-450]), increased membrane carrier protein abundance and electrogenic glucose transport capacity in SGLT1-expressing Xenopus oocytes. Thus TTBK2 is a completely novel regulator of Na(+)-coupled glucose transport.
Downregulation of ClC-2 by JAK2
2012-01-01

JAK2 (Janus kinase-2) is activated by cell shrinkage and may thus participate in cell volume regulation. Cell volume regulatory ion channels include the small conductance Cl(-) channels ClC-2. The present study thus explored whether JAK2 influences ClC-2 activity. To this end, ClC-2 was expressed in Xenopus oocytes with or without wild type JAK2, active (V617F)JAK2 or inactive (K882E)JAK2 and the Cl(-) channel activity determined by dual electrode voltage clamp. Expression of ClC-2 was followed by a marked increase of cell membrane conductance. The conductance was significantly decreased following coexpression of JAK2 or (V617F)JAK2, but not by coexpression of (K882E)JAK2. Exposure of the oocytes expressing ClC-2 together with (V617F)JAK2 to the JAK2 inhibitor AG490 (40 μM) resulted in a gradual increase of the conductance. According to chemiluminescence JAK2 decreased the channel protein abundance in the cell membrane. The decline of conductance in ClC-2 and (V617F)JAK2 coexpressing oocytes following inhibition of channel protein insertion by brefeldin A (5 μM) was similar in oocytes expressing ClC-2 with (V617F)JAK2 and oocytes expressing ClC-2 alone, indicating that (V617F)JAK2 might slow channel protein insertion into rather than accelerating channel protein retrieval from the cell membrane. In conclusion, JAK2 down-regulates ClC-2 activity and thus counteracts Cl(-) exit, an effect which may impact on cell volume regulation.
Does Inflammation Determine Whether Obesity Is Metabolically Healthy or Unhealthy? The Aging Perspective
2012-01-01

Obesity is a major health issue in developed as well as developing countries. While obesity is associated with relatively good health status in some individuals, it may become a health issue for others. Obesity in the context of inflammation has been studied extensively. However, whether obesity in its various forms has the same adverse effects is a matter of debate and requires further research. During its natural history, metabolically healthy obesity (MHO) converts into metabolically unhealthy obesity (MUHO). What causes this transition to occur and what is the role of obesity-related mediators of inflammation during this transition is discussed in this paper.
A crucial role of Mim2 in the biogenesis of mitochondrial outer membrane proteins
2012-01-01

Most of the mitochondrial outer membrane (MOM) proteins contain helical transmembrane domains. Some of the single span proteins and all known multiple span proteins are inserted into the membrane in a pathway which depends on the MOM protein Mitochondrial Import 1 (Mim1). So far it has been unknown whether additional proteins are required for this process. Here we describe the identification and characterization of Mim2, a novel protein of the mitochondrial outer membrane that has a crucial role in the biogenesis of MOM helical proteins. Mim2 physically and genetically interacts with Mim1 and both proteins form the MIM complex. Cells lacking Mim2 exhibit a severely reduced growth rate and lower steady state levels of helical MOM proteins. In addition, absence of Mim2 leads to compromised assembly of the translocase of the outer mitochondrial membrane (TOM complex), hampered mitochondrial protein import, and defects in mitochondrial morphology. In summary, the current study demonstrates that Mim2 is a novel central player in the biogenesis of MOM proteins.
The role of cluster formation and metastable liquid—liquid phase separation in protein crystallization
2012-01-01

We discuss the phase behavior and in particular crystallization of a model globular protein (beta-lactoglobulin) in solution in the presence of multivalent electrolytes. It has been shown previously that negatively charged globular proteins at neutral pH in the presence of multivalent counterions undergo a "re-entrant condensation (RC)" phase behavior (Zhang et al., Phys. Rev. Lett., 2008, 101, 148101), i.e. a phase-separated regime occurs in between two critical salt concentrations, c* &lt; c**, giving a metastable liquid-liquid phase separation (LLPS). Crystallization from the condensed regime has been observed to follow different mechanisms. Near c*, crystals grow following a classic nucleation and growth mechanism; near c**, the crystallization follows a two-step crystallization mechanism, i.e, crystal growth follows a metastable LLPS. In this paper, we focus on the two-step crystal growth near c**. SAXS measurements indicate that proteins form clusters in this regime and the cluster size increases approaching c**. Upon lowering the temperature, in situ SAXS studies indicate that the clusters can directly form both a dense liquid phase and protein crystals. During the crystal growth, the metastable dense liquid phase is dissolved. Based on our observations, we discuss a nucleation mechanism starting from clusters in the dilute phase from a metastable LLPS. These protein clusters behave as the building blocks for nucleation, while the dense phase acts as a reservoir ensuring constant protein concentration in the dilute phase during crystal growth.
Asking sensitive questions: A statistical power analysis of randomized response models.
2012-01-01

This article derives the power curves for a Wald test that can be applied to randomized response models when small prevalence rates must be assessed (e.g., detecting doping behavior among elite athletes). These curves enable the assessment of the statistical power that is associated with each model (e.g., Warner's model, crosswise model, unrelated question model, forced-choice models, item count model, cheater detection model). This power analysis can help in choosing the optimal model and sample size and in setting model parameters in survey studies. The general framework can be applied to all existing randomized response model versions. The Appendix of this article contains worked-out numerical examples to demonstrate the power analysis for each specific model.
Idiopathic Polyhydramnios and Postnatal Abnormalities
2012-01-01

&lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; To investigate the proportion and type of fetal anomalies that are associated with polyhydramnios and to examine whether in cases with idiopathic polyhydramnios during the course of pregnancy and fetal anomalies only diagnosed after birth, antenatal characteristics differ. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; This was a retrospective study involving all pregnancies with polyhydramnios defined by a deepest pool of amniotic fluid ≥8 cm and a detailed ultrasound examination, a 75 g glucose tolerance test and a TORCH serology. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Between 2004 and 2010, 272 pregnancies fulfilled the inclusion criteria. In 89 (32.7%) and 65 (23.9%) cases, there was a fetal anomaly or diabetes. In 118 (43.4%) pregnancies, polyhydramnios was classified as idiopathic. In 11 (9.3%) of the 118 fetuses, an anomaly was found after birth, mainly gastrointestinal atresia. In these cases, median deepest pool of amniotic fluid was 9.6 cm, and median estimated fetal weight was at the 69th centile, whereas in cases without anomalies diagnosed after birth, median deepest pool was 9.0 cm and median estimated fetal weight at the 90th centile (Mann-Whitney U test: deepest pool p = 0.116, and estimated fetal weight centile p = 0.377). There was also no difference in the maternal and gestational age distribution of these cases (Mann-Whitney U test: maternal age p = 0.293, and gestational age p = 0.499). &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; In about 40% of pregnancies, polyhydramnios remains unexplained during the course of pregnancy. In 10% of these cases, an anomaly will only be found after birth. In this group, antenatal characteristics such as amniotic fluid volume, estimated fetal weight or gestational and maternal age at the time of diagnosis do not help to detect these anomalies before birth.
The Role of Job Satisfaction, Job Ambivalence, and Emotions at Work in Predicting Organizational Citizenship Behavior
2012-01-01

Various mostly cross-sectional studies have established that job satisfaction is related to organizational citizenship behavior (OCB). A major goal of the present study was to show that job ambivalence (i.e., the coexistence of positive and negative job evaluations) moderates the job satisfaction-OCB relationship. To this end, job satisfaction, job ambivalence, frequency of positive and negative emotions at work, dispositional positive and negative affectivity, and OCB were gathered from employees at time 1. About 2 months later, OCB was assessed by both peer-ratings and self-ratings. As predicted, the relationship between job satisfaction and both peer-rated and self-rated OCB was stronger the lower the experienced job ambivalence. Further findings showed that job satisfaction mediated the relationship between positive emotions and OCB, and that this indirect effect of positive emotions was conditional on low job ambivalence. Negative emotions, though negatively related to OCB, did not contribute to predicting OCB beyond positive emotions.
Pyrrhotite remagnetizations in the Himalaya: a review
2012-01-01

Abstract This paper reviews results on the nature and thermo-tectonic interpretation of widespread pyrrhotite remagnetizations in the Himalaya. Throughout the last two decades a large dataset has been acquired, in particular from low-grade metamorphic rocks of the Tethyan Sedimentary Series (TSS). The nature of this magnetization is a thermoremanence when the peak metamorphic temperature T max exceeded the Curie temperature ( T c c. 325 °C) of pyrrhotite; in this case the remanence age can be related to last metamorphic cooling. For T max &lt; T c , the remanence can be of chemical, thermochemical or thermoremanent origin. Cooling ages show a systematic trend of c. 50–20 Ma from the western to the eastern Himalaya. The pyrrhotite remagnetizations post-date main Himalayan folding and record late orogenic long-wavelength rotations and tiltings around vertical and horizontal axes. Remanence directions in the western Himalaya are well matching with large-scale deformations of rotational shortening and oroclinal bending, while in the central and eastern Himalaya they are predominantly controlled by meso-scale effects due to crustal doming. Stable pyrrhotite remanences are especially typical for low-grade marly limestones in the TSS, but were also found in medium-grade rocks of the Lesser Himalaya, highly metamorphic rocks of the Higher Himalayan Crystalline and diorite dykes intruding into the TSS.
Microbial Iron(II) Oxidation in Littoral Freshwater Lake Sediment: The Potential for Competition between Phototrophic vs. Nitrate-Reducing Iron(II)-Oxidizers
2012-01-01

The distribution of neutrophilic microbial iron oxidation is mainly determined by local gradients of oxygen, light, nitrate and ferrous iron. In the anoxic top part of littoral freshwater lake sediment, nitrate-reducing and phototrophic Fe(II)-oxidizers compete for the same e(-) donor; reduced iron. It is not yet understood how these microbes co-exist in the sediment and what role they play in the Fe cycle. We show that both metabolic types of anaerobic Fe(II)-oxidizing microorganisms are present in the same sediment layer directly beneath the oxic-anoxic sediment interface. The photoferrotrophic most probable number counted 3.4·10(5) cells·g(-1) and the autotrophic and mixotrophic nitrate-reducing Fe(II)-oxidizers totaled 1.8·10(4) and 4.5·10(4) cells·g(-1) dry weight sediment, respectively. To distinguish between the two microbial Fe(II) oxidation processes and assess their individual contribution to the sedimentary Fe cycle, littoral lake sediment was incubated in microcosm experiments. Nitrate-reducing Fe(II)-oxidizing bacteria exhibited a higher maximum Fe(II) oxidation rate per cell, in both pure cultures and microcosms, than photoferrotrophs. In microcosms, photoferrotrophs instantly started oxidizing Fe(II), whilst nitrate-reducing Fe(II)-oxidizers showed a significant lag-phase during which they probably use organics as e(-) donor before initiating Fe(II) oxidation. This suggests that they will be outcompeted by phototrophic Fe(II)-oxidizers during optimal light conditions; as phototrophs deplete Fe(II) before nitrate-reducing Fe(II)-oxidizers start Fe(II) oxidation. Thus, the co-existence of the two anaerobic Fe(II)-oxidizers may be possible due to a niche space separation in time by the day-night cycle, where nitrate-reducing Fe(II)-oxidizers oxidize Fe(II) during darkness and phototrophs play a dominant role in Fe(II) oxidation during daylight. Furthermore, metabolic flexibility of Fe(II)-oxidizing microbes may play a paramount role in the conservation of the sedimentary Fe cycle.