julilili42/papers huggingface dataset:
Regulation of ClC-2 Activity by SPAK and OSR1
2014-01-01

&lt;b&gt;&lt;i&gt;Background/Aims: &lt;/i&gt;&lt;/b&gt;SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1) are powerful regulators of diverse transport processes. Both kinases are activated by cell shrinkage and participate in stimulation of regulatory cell volume increase (RVI). Execution of RVI involves inhibition of Cl&lt;sup&gt;-&lt;/sup&gt; channels. The present study explored whether SPAK and/or OSR1 regulate the activity of the Cl&lt;sup&gt;-&lt;/sup&gt; channel ClC-2. &lt;b&gt;&lt;i&gt;Methods: &lt;/i&gt;&lt;/b&gt;To this end, ClC-2 was expressed in &lt;i&gt;Xenopus laevis&lt;/i&gt; oocytes with or without additional expression of wild type SPAK, constitutively active SPAK&lt;sup&gt;T233E&lt;/sup&gt;, WNK1 insensitive inactive SPAK&lt;sup&gt;T233A&lt;/sup&gt;, catalytically inactive SPAK&lt;sup&gt;D212A&lt;/sup&gt;, wild type OSR1, constitutively active OSR1&lt;sup&gt;T185E&lt;/sup&gt;, WNK1 insensitive inactive OSR1&lt;sup&gt;T185A&lt;/sup&gt;, and catalytically inactive OSR1&lt;sup&gt;D164A&lt;/sup&gt;. Cl&lt;sup&gt;-&lt;/sup&gt; channel activity was determined by dual electrode voltage clamp. &lt;b&gt;&lt;i&gt;Results: &lt;/i&gt;&lt;/b&gt;Expression of ClC-2 was followed by the appearance of a conductance (G&lt;sub&gt;Cl&lt;/sub&gt;), which was significantly decreased following coexpression of wild-type SPAK, SPAK&lt;sup&gt;T233E&lt;/sup&gt;, wild type OSR1 or OSR1&lt;sup&gt;T185E&lt;/sup&gt;, but not by coexpression of SPAK&lt;sup&gt;T233A&lt;/sup&gt;, SPAK&lt;sup&gt;D212A&lt;/sup&gt;, OSR1&lt;sup&gt;T185A&lt;/sup&gt;, or OSR1&lt;sup&gt;D164A&lt;/sup&gt;. Inhibition of ClC-2 insertion by brefeldin A (5 μM) resulted in a decline of G&lt;sub&gt;Cl&lt;/sub&gt; which was similar in the absence and presence of SPAK or OSR1, suggesting that SPAK and OSR1 did not accelerate the retrieval of ClC-2 protein from the cell membrane. &lt;b&gt;&lt;i&gt;Conclusion: &lt;/i&gt;&lt;/b&gt;SPAK and OSR1 are powerful negative regulators of the cell volume regulatory Cl&lt;sup&gt;-&lt;/sup&gt; channel ClC-2.
Vowel articulation affected by word frequency
2014-01-01

A frequently replicated finding is that the frequency of words affects their phonetic shape. In English, high frequency words have been shown to contain more centralized vowels than low frequency words. By contrast, a recent study on vowel articulation in German has shown a contrary finding. At the gestural level, tongue movements in HF words showed more extensive vowel targets and less coarticulationwith consonants. This paper further evaluates the later finding by taking into account a large set of verbs covering the continuum between high and low frequency. In addition to frequency the effects of two factors were analyzed: inflection (sagt vs. sagen) and speech rate (normal vs. fast). Our results imply that language experience increases the proficiency with which words are articulated: speakers are able to plan and target tongue movements earlier.
SPAK Dependent Regulation of Peptide Transporters PEPT1 and PEPT2
2014-01-01

&lt;b&gt;&lt;i&gt;Background/Aims: &lt;/i&gt;&lt;/b&gt;SPAK (STE20-related proline/alanine-rich kinase) is a powerful regulator of renal tubular ion transport and blood pressure. Moreover, SPAK contributes to the regulation of cell volume. Little is known, however, about a role of SPAK in the regulation or organic solutes. The present study thus addressed the influence of SPAK on the peptide transporters PEPT1 and PEPT2. &lt;b&gt;&lt;i&gt;Methods: &lt;/i&gt;&lt;/b&gt;To this end, cRNA encoding PEPT1 or PEPT2 were injected into &lt;i&gt;Xenopus laevis&lt;/i&gt; oocytes without or with additional injection of cRNA encoding wild-type, SPAK, WNK1 insensitive inactive &lt;sup&gt;T233A&lt;/sup&gt;SPAK, constitutively active &lt;sup&gt;T233E&lt;/sup&gt;SPAK, and catalytically inactive &lt;sup&gt;D212A&lt;/sup&gt;SPAK. Electrogenic peptide (glycine-glycine) transport was determined by dual electrode voltage clamp and PEPT2 protein abundance in the cell membrane by chemiluminescence. Intestinal electrogenic peptide transport was estimated from peptide induced current in Ussing chamber experiments of jejunal segments isolated from gene targeted mice expressing SPAK resistant to WNK-dependent activation (&lt;i&gt;spak&lt;/i&gt;&lt;sup&gt;&lt;i&gt;tg/tg&lt;/i&gt;&lt;/sup&gt;) and respective wild-type mice (&lt;i&gt;spak&lt;/i&gt;&lt;sup&gt;&lt;i&gt;+/+&lt;/i&gt;&lt;/sup&gt;). &lt;b&gt;&lt;i&gt;Results: &lt;/i&gt;&lt;/b&gt;In PEPT1 and in PEPT2 expressing oocytes, but not in oocytes injected with water, the dipeptide gly-gly (2 mM) generated an inward current, which was significantly decreased following coexpression of SPAK. The effect of SPAK on PEPT1 was mimicked by &lt;sup&gt;T233E&lt;/sup&gt;SPAK, but not by &lt;sup&gt;D212A&lt;/sup&gt;SPAK or &lt;sup&gt;T233A&lt;/sup&gt;SPAK. SPAK decreased maximal peptide induced current of PEPT1. Moreover, SPAK decreased carrier protein abundance in the cell membrane of PEPT2 expressing oocytes. In intestinal segments gly-gly generated a current, which was significantly higher in &lt;i&gt;spak&lt;/i&gt;&lt;sup&gt;&lt;i&gt;tg/tg&lt;/i&gt;&lt;/sup&gt; than in &lt;i&gt;spak&lt;/i&gt;&lt;sup&gt;&lt;i&gt;+/+&lt;/i&gt;&lt;/sup&gt; mice. &lt;b&gt;&lt;i&gt;Conclusion: &lt;/i&gt;&lt;/b&gt;SPAK is a powerful regulator of peptide transporters PEPT1 and PEPT2.
Preoperative C-Reactive Protein in the Serum: A Prognostic Biomarker for Upper Urinary Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy
2014-01-01

&lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; To investigate the impact of preoperative serum C-reactive protein (CRP) on clinicopathological features and prognosis in patients with upper tract urothelial cancer (UTUC) after radical nephroureterectomy (RNU). &lt;b&gt;&lt;i&gt;Patients and&lt;/i&gt;&lt;/b&gt;&lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Data of 265 patients from three German centers who underwent RNU for UTUC without neoadjuvant chemotherapy between 1990 and 2012 were evaluated. Mean follow-up was 37 months (interquartile range 9-48). CRP was analyzed as a categorical and continuous variable for the prediction of recurrence-free survival (RFS), disease-specific survival (DSS) and all-cause survival (ACS) using uni- and multivariate Cox regression analyses. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The optimal cutoff for CRP was calculated by the Youden index at 0.90 mg/dl. Elevated CRP was significantly associated with pT3/4 and pN+ in a preoperative model including age, gender, tumor multifocality, tumor localization and the Eastern Cooperative Oncology Group Performance Status. In a multivariable Cox regression model adjusted for features significant in univariable analysis, categorized and continuous CRP levels were both independent predictors for RFS [hazard ratio (HR) 1.18, p = 0.050; HR 1.03, p = 0.012] and DSS (HR 1.61, p = 0.026; HR 1.06, p = 0.001). Continuous CRP was an independent predictor for ACS (HR 1.05, p = 0.036). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Elevated preoperative CRP is significantly associated with aggressive tumor biology and an independent predictor for poor survival after RNU. Preoperative serum CRP represents an easily obtainable and cost-effective marker in UTUC and may help in counseling patients with regard to operative management and/or adjuvant or neoadjuvant therapies.
Downregulation of Peptide Transporters PEPT1 and PEPT2 by Oxidative Stress Responsive Kinase OSR1
2014-01-01

&lt;b&gt;&lt;i&gt;Background/Aims: &lt;/i&gt;&lt;/b&gt;OSR1 (oxidative-stress-responsive kinase 1) participates in the regulation of renal tubular ion transport, cell volume and blood pressure. Whether OSR1 contributes to the regulation of organic solute transport remained; however, elusive. The present study thus explored the OSR1 sensitivity of the peptide transporters PEPT1 and PEPT2. &lt;b&gt;&lt;i&gt;Methods: &lt;/i&gt;&lt;/b&gt;cRNA encoding PEPT1 or PEPT2 were injected into &lt;i&gt;Xenopus&lt;/i&gt; oocytes without or with additional injection of cRNA encoding wild-type OSR1, WNK1 insensitive inactive &lt;sup&gt;T185A&lt;/sup&gt;OSR1, constitutively active &lt;sup&gt;T185E&lt;/sup&gt;OSR1, and catalytically inactive &lt;sup&gt;D164A&lt;/sup&gt;OSR1. Electrogenic peptide (glycine-glycine) transport was determined by dual electrode voltage clamp, the abundance of hemagglutinin-tagged PEPT2 (PEPT2-HA) by chemiluminescence. &lt;b&gt;&lt;i&gt;Results: &lt;/i&gt;&lt;/b&gt;In &lt;i&gt;Xenopus&lt;/i&gt; oocytes injected with cRNA encoding PEPT1 or PEPT2, but not in oocytes injected with water, the dipeptide gly-gly (2 mM) generated an appreciable inward current (I&lt;sub&gt;gly-gly&lt;/sub&gt;). Coexpression of OSR1 significantly decreased I&lt;sub&gt;gly-gly&lt;/sub&gt; in both PEPT1 and PEPT2 expressing oocytes. The effect of OSR1 coexpression on I&lt;sub&gt;gly-gly&lt;/sub&gt; in PEPT1 expressing oocytes was mimicked by coexpression of &lt;sup&gt;T185E&lt;/sup&gt;OSR1, but not of &lt;sup&gt;D164A&lt;/sup&gt;OSR1 or &lt;sup&gt;T185A&lt;/sup&gt;OSR1. Kinetic analysis revealed that coexpression of OSR1 decreased maximal I&lt;sub&gt;gly-gly&lt;/sub&gt;. OSR1 further decreased the PEPT2-HA protein abundance in the cell membrane. &lt;b&gt;&lt;i&gt;Conclusion: &lt;/i&gt;&lt;/b&gt;OSR1 has the capacity to downregulate the peptide transporters PEPT1 and PEPT2 by decreasing the carrier protein abundance in the cell membrane.
Longterm-habituation of the startle response in mice is stimulus modality, but not context specific
2014-01-01

In mice, the specificity of longterm-habituation (LTH) of startle was tested in two experiments. In two strains of mice (C57Bl/6 and C3H) there was pronounced LTH over 10 days of acoustic stimulation in two different contexts of startle measurement. (We found LTH to be greater after stimulation with 14 kHz sine stimuli compared to noise or tactile stimuli). A change of context showed LTH to be independent of context, i.e., startle LTH in mice is a non-associative learning process. In the second experiment, 9 days of acoustic or tactile stimulation were given to C57B/6 mice. Both stimulus modalities produced LTH. When on the 10th day stimuli of the other modality were given, in both cases the long term habituated group showed no lower startle amplitude than a non-stimulated control group. This indicates LTH is stimulus-modality specific. Altogether, our results show that in mice-very similar to rats-LTH of startle is stimulus modality, but not context specific. In addition we found two indications that the LTH action site is on the sensory branch of the startle circuit.
Tff3 is Expressed in Neurons and Microglial Cells
2014-01-01

The neuronal expression of Tff3 is in line with a function of a typical neuropeptide influencing, e.g., fear, memory, depression and motoric skills. The expression in activated microglial cells, which is demonstrated here for the first time, points towards a possible function for Tff3 in immune reactions in the CNS. This opens a plethora of additional possible functions for Tff3 including synaptic plasticity and cognition as well as during neuroinflammatory diseases and psychiatric disorders.
Systematics and phylogeny of middle Miocene Cervidae (Mammalia) from Mae Moh Basin (Thailand) and a paleoenvironmental estimate using enamel isotopy of sympatric herbivore species
2014-01-01

ABSTRACTThe primitive deer (subfamily Lagomerycinae) <i>Lagomeryx</i> and <i>Stephanocemas</i> are characterized primarily by their palmate antlers. Two lagomerycines, <i>Lagomeryx manai</i>, sp. nov., and <i>Stephanocemas rucha</i>, are described for the first time from Q and K coal layers of the late middle Miocene (13.4–13.2 Ma) Mae Moh Basin in northern Thailand. A species-level phylogeny of the <i>Ligeromeryx</i>-<i>Lagomeryx</i> clade, based on cranial appendages, reconstructs <i>Lagomeryx manai</i>, n. sp., as a derived species of <i>Lagomeryx</i>, sister group of <i>Lagomeryx complicidens</i>. This study suggests that the large species of <i>Lagomeryx</i> are restricted geographically to Asia and dispersed to Southeast Asia at the latest during late middle Miocene, where they are represented by <i>Lagomeryx manai</i>, n. sp. The paleoenvironmental studies of five Mae Moh mammalian taxa, a cervid (<i>Lagomeryx manai</i>, n. sp.), an indeterminate bovid, a suid (<i>Conohyus thailandicus</i>), a rhinoceros (<i>Gaindatherium</i> sp.), and a proboscidean (<i>Stegolophodon</i> sp.), investigated with stable carbon and oxygen isotope analyses of tooth enamel, indicate that the Mae Moh mammals inhabited a wide range of habitats from woodlands to grasslands in a C3-plant-dominated environment. The new species of <i>Lagomeryx</i> seems to have been living in an open environment, contrary to its European relatives. The serial isotopic samples also support that Mae Moh herbivores probably lived in a low-seasonal climate during the late middle Miocene of northern Thailand. SUPPLEMENTAL DATA—Supplemental materials are available for this article for free at www.tandfonline.com/UJVP
Stepwise Application of Urine Markers to Detect Tumor Recurrence in Patients Undergoing Surveillance for Non-Muscle-Invasive Bladder Cancer
2014-01-01

Background . The optimal use of urine markers in the surveillance of non-muscle-invasive bladder cancer (NMIBC) remains unclear. Aim of the present study was to investigate the combined and stepwise use of the four most broadly available urine markers to detect tumor recurrence in patients undergoing surveillance of NMIBC. Patients and Methods . 483 patients with history of NMIBC were included. Cytology, UroVysion, fluorescence in situ hybridization (FISH), immunocytology (uCyt+), and NMP22 ELISA were performed before surveillance cystoscopy. Characteristics of single tests and combinations were assessed by contingency analysis. Results . 128 (26.5%) patients had evidence of tumor recurrence. Sensitivities and negative predictive values (NPVs) of the single tests ranged between 66.4–74.3 and 82.3–88.2%. Two-marker combinations showed sensitivities and NPVs of 80.5–89.8 and 89.5–91.2%. A stepwise application of the two-test combinations with highest accuracy (cytology and FISH; cytology and uCyt+; uCyt+ and FISH) showed NPVs for high-risk recurrences (G3/Cis/pT1) of 98.8, 98.8, and 99.1%, respectively. Conclusions . Combinations of cytology, FISH, immunocytology, and NMP22 show remarkable detection rates for recurrent NMIBC. Stepwise two-test combinations of cytology, FISH, and immunocytology have a low probability of missing a high-risk tumor. The high sensitivities may justify the use of these combinations in prospective studies assessing the use of urine markers to individualize intervals between cystoscopies during follow-up.
Solidification of a colloidal hard sphere like model system approaching and crossing the glass transition
2014-01-01

We investigated the process of vitrification and crystallization in a model system of colloidal hard spheres. The kinetics of the solidification process was measured using time resolved static light scattering, while the time evolution of the dynamic properties was determined using time resolved dynamic light scattering. By performing further analysis we confirm that solidification of hard sphere colloids is mediated by precursors. Analyzing the dynamic properties we can show that the long time dynamics and thus the shear rigidity of the metastable melt is highly correlated with the number density of solid clusters (precursors) nucleated. In crystallization these objects convert into highly ordered crystals whereas in the case of vitrification this conversion is blocked and the system is (temporarily) locked in the metastable precursor state. From the early stages of solidification one cannot clearly conclude whether the melt will crystallize or vitrify. Furthermore our data suggests that colloidal hard sphere glasses can crystallize via homogeneous nucleation.
Plasma membrane-association of SAUL1-type plant U-box armadillo repeat proteins is conserved in land plants
2014-01-01

Post-translational protein modification plays a pivotal role in the regulation and specific turnover of proteins. One of these important modifications is the ubiquitination of target proteins, which can occur at distinct cellular compartments. At the plasma membrane, ubiquitination regulates the internalization and thus trafficking of membrane proteins such as receptors and channels. The Arabidopsis plant U-box (PUB) armadillo repeat (PUB-ARM) ubiquitin ligase SAUL1 (SENESCENCE-ASSOCIATED UBIQUITIN LIGASE1) is part of the ubiquitination machinery at the plasma membrane. In contrast to most other PUB-ARM proteins, SAUL1 carries additional C-terminal ARM repeats responsible for plasma membrane-association. Here, we demonstrated that the C-terminal ARM repeat domain is also essential and sufficient to mediate plasma membrane-association of the closest Arabidopis paralog AtPUB43. We investigated targeting of PUB-ARM ubiquitin ligases of different plant species to find out whether plasma membrane-association of SAUL1-type PUB-ARM proteins is conserved. Phylogenetic analysis identified orthologs of SAUL1 in these plant species. Intracellular localization of transiently expressed GFP fusion proteins revealed that indeed plasma membrane-association due to additional C-terminal ARM repeats represents a conserved feature of SAUL1-type proteins. Analyses of transgenic Arabidopsis plants overexpressing N-terminally masked or truncated proteins revealed that interfering with the function of SAUL1-type proteins resulted in severe growth defects. Our results suggest an ancient origin of ubiquitination at the plasma membrane in the evolution of land plants.
A-Legality: Journey to the borders of law. In dialogue with Hans Lindahl
2014-01-01

This paper delineates and discusses the overall theoretical trajectory of Hans Lindahl’s work Fault Lines of Globalization. Furthermore, through a strategy of joint thinking – or dialogue – with the author, the article hits a double target. On the one hand, it gives the reader the oppor-tunity to better grasp some aspects and features of the author’s philosophical background. On the other, it fleshes out some crucial passages of the book with the aim of a further clarification and more accurate inspection.
Does rTMS Alter Neurocognitive Functioning in Patients with Panic Disorder/Agoraphobia? An fNIRS-Based Investigation of Prefrontal Activation during a Cognitive Task and Its Modulation via Sham-Controlled rTMS
2014-01-01

Objectives . Neurobiologically, panic disorder (PD) is supposed to be characterised by cerebral hypofrontality. Via functional near-infrared spectroscopy (fNIRS), we investigated whether prefrontal hypoactivity during cognitive tasks in PD-patients compared to healthy controls (HC) could be replicated. As intermittent theta burst stimulation (iTBS) modulates cortical activity, we furthermore investigated its ability to normalise prefrontal activation. Methods . Forty-four PD-patients, randomised to sham or verum group, received 15 iTBS-sessions above the left dorsolateral prefrontal cortex (DLPFC) in addition to psychoeducation. Before first and after last iTBS-treatment, cortical activity during a verbal fluency task was assessed via fNIRS and compared to the results of 23 HC. Results . At baseline, PD-patients showed hypofrontality including the DLPFC, which differed significantly from activation patterns of HC. However, verum iTBS did not augment prefrontal fNIRS activation. Solely after sham iTBS, a significant increase of measured fNIRS activation in the left inferior frontal gyrus (IFG) during the phonological task was found. Conclusion . Our results support findings that PD is characterised by prefrontal hypoactivation during cognitive performance. However, verum iTBS as an “add-on” to psychoeducation did not augment prefrontal activity. Instead we only found increased fNIRS activation in the left IFG after sham iTBS application. Possible reasons including task-related psychophysiological arousal are discussed.
Carbon and nitrogen isotope analyses of human and dog diet in the Okhotsk culture: perspectives from the Moyoro site, Japan
2014-01-01

The Okhotsk people were sedentary hunter-gatherer-fishers who lived and prospered in Sakhalin, Hokkaido, and the Kurile Islands during the fifth–thirteenth centuries AD. They expanded rapidly along the north-eastern coast of Hokkaido where archaeological evidence suggests an increasing dependence on hunting marine mammals. In this study, we present the results of carbon and nitrogen isotope analyses of 18 faunal (including two domesticated dogs) and 58 adult human skeletons excavated from the Moyoro site of the Okhotsk culture in eastern Hokkaido. Although the mean human isotope ratios did not differ between sexes, the variances of carbon isotope ratios were significantly greater in males. Carbon and nitrogen isotope ratios suggest that the Moyoro humans and dogs heavily depended on marine foods for their dietary protein intake. The Bayesian mixing model suggests that humans obtained a maximum of 80–90% of their dietary protein from marine mammals, whereas domesticated dogs obtained 2–33%, 3–40%, and 5–45% of dietary protein from brackish-water fish, marine fish, and marine mammals, respectively. This suggests an avoidance of significant dietary overlap between the sympatrically living humans and dogs at the Moyoro site. Significant maritime adaptation would have enabled the subsistence of the Okhotsk people in the harsh northern environment of Hokkaido.
Inflammatory stimulation preserves physiological properties of retinal ganglion cells after optic nerve injury
2014-01-01

Axonal injury in the optic nerve is associated with retinal ganglion cell (RGC) degeneration and irreversible loss of vision. However, inflammatory stimulation (IS) by intravitreal injection of Pam3Cys transforms RGCs into an active regenerative state enabling these neurons to survive injury and to regenerate axons into the injured optic nerve. Although morphological changes have been well studied, the functional correlates of RGCs transformed either into a de- or regenerating state at a sub-cellular level remain unclear. In the current study, we investigated the signal propagation in single intraretinal axons as well as characteristic activity features of RGCs in a naive, a degenerative or a regenerative state in ex vivo retinae 1 week after either optic nerve cut alone (ONC) or additional IS (ONC + IS). Recordings of single RGCs using high-density microelectrode arrays demonstrate that the mean intraretinal axonal conduction velocity significantly decreased within the first week after ONC. In contrast, when ONC was accompanied by regenerative Pam3Cys treatment the mean intraretinal velocity was undistinguishable from control RGCs, indicating a protective effect on the proximal axon. Spontaneous RGC activity decreased for the two most numerous RGC types (ON- and OFF-sustained cells) within one post-operative week, but did not significantly increase in RGCs after IS. The analysis of light-induced activity revealed that RGCs in ONC animals respond on average later and with fewer spikes than control RGCs. IS significantly improved the responsiveness of the two studied RGC types. These results show that the transformation into a regenerative state by IS preserves, at least transiently, the physiological functional properties of injured RGCs.