julilili42/papers huggingface dataset:
Plant diversity effects on the water balance of an experimental grassland
2013-12-12

ABSTRACT In the literature, contrasting effects of plant species richness on the soil water balance are reported. Our objective was to assess the effects of plant species and functional richness and functional identity on soil water contents and water fluxes in the experimental grassland of the Jena Experiment. The Jena Experiment comprises 86 plots on which plant species richness (0, 1, 2, 4, 8, 16, and 60) and functional group composition (zero to four functional groups: legumes, grasses, tall herbs, and small herbs) were manipulated in a factorial design. We recorded meteorological data and soil water contents of the 0·0–0·3 and 0·3–0·7 m soil layers and calculated actual evapotranspiration ( ETa ), downward flux ( DF ), and capillary rise with a soil water balance model for the period 2003–2007. Missing water contents were estimated with a Bayesian hierarchical model. Species richness decreased water contents in subsoil during wet soil conditions. Presence of tall herbs increased soil water contents in topsoil during dry conditions and decreased soil water contents in subsoil during wet conditions. Presence of grasses generally decreased water contents in topsoil, particularly during dry phases; increased ETa and decreased DF from topsoil; and decreased ETa from subsoil. Presence of legumes, in contrast, decreased ETa and increased DF from topsoil and increased ETa from subsoil. Species richness probably resulted in complementary water use. Specific functional groups likely affected the water balance via specific root traits (e.g. shallow dense roots of grasses and deep taproots of tall herbs) or specific shading intensity caused by functional group effects on vegetation cover. Copyright © 2013 John Wiley &amp; Sons, Ltd.
Halogens (F, Cl and Br) at Oldoinyo Lengai volcano (Tanzania): Effects of magmatic differentiation, silicate–natrocarbonatite melt separation and surface alteration of natrocarbonatite
2013-12-12

Halogen abundances of natrocarbonatites and their alteration products from Oldoinyo Lengai (Tanzania) are compared to those of associated silicate rocks and to various calcite carbonatites from eleven occurrences worldwide. Fresh natrocarbonatites are extremely enriched in F (up to 3.6 wt.%), Cl (up to 5.9 wt.%) and Br (up to 100 μg/g). During meteoric alteration, however, the major Cl- and Br-bearing minerals (mainly sylvite and gregoryite) are easily dissolved, leaving behind residual materials with relatively low Cl (≤ 1000 μg/g) and Br (≤ 15 μg/g) contents. The comparatively low Cl/Br ratios suggest preferential leaching of Cl relative to Br during alteration. At the same time, F is passively enriched as fluorite remains relatively stable during alteration. In the associated silicate rocks at Oldoinyo Lengai concentrations of all three halogens increase from primitive olivine melilitite to evolved combeite–wollastonite nephelinite, demonstrating their incompatible behavior during magmatic differentiation. Relatively constant Cl/Br ratios, but strongly decreasing F/Cl ratios, in these samples are explained by moderately incompatible behavior for F compared to pronounced and very similar incompatibilities for Cl and Br. Our data further imply that during silicate–natrocarbonatite melt separation all three halogens show a strong affinity for the natrocarbonatite. F and Cl are equally enriched in the natrocarbonatite while Cl and Br are slightly fractionated from each other with a preferential partitioning of Cl relative to Br into the natrocabonatite melt.
TFpredict and SABINE: Sequence-Based Prediction of Structural and Functional Characteristics of Transcription Factors
2013-12-12

One of the key mechanisms of transcriptional control are the specific connections between transcription factors (TF) and cis-regulatory elements in gene promoters. The elucidation of these specific protein-DNA interactions is crucial to gain insights into the complex regulatory mechanisms and networks underlying the adaptation of organisms to dynamically changing environmental conditions. As experimental techniques for determining TF binding sites are expensive and mostly performed for selected TFs only, accurate computational approaches are needed to analyze transcriptional regulation in eukaryotes on a genome-wide level. We implemented a four-step classification workflow which for a given protein sequence (1) discriminates TFs from other proteins, (2) determines the structural superclass of TFs, (3) identifies the DNA-binding domains of TFs and (4) predicts their cis-acting DNA motif. While existing tools were extended and adapted for performing the latter two prediction steps, the first two steps are based on a novel numeric sequence representation which allows for combining existing knowledge from a BLAST scan with robust machine learning-based classification. By evaluation on a set of experimentally confirmed TFs and non-TFs, we demonstrate that our new protein sequence representation facilitates more reliable identification and structural classification of TFs than previously proposed sequence-derived features. The algorithms underlying our proposed methodology are implemented in the two complementary tools TFpredict and SABINE. The online and stand-alone versions of TFpredict and SABINE are freely available to academics at http://www.cogsys.cs.uni-tuebingen.de/software/TFpredict/ and http://www.cogsys.cs.uni-tuebingen.de/software/SABINE/.
From PII Signaling to Metabolite Sensing: A Novel 2-Oxoglutarate Sensor That Details PII - NAGK Complex Formation
2013-12-12

The widespread PII signal transduction proteins are known for integrating signals of nitrogen and energy supply and regulating cellular behavior by interacting with a multitude of target proteins. The PII protein of the cyanobacterium Synechococcus elongatus forms complexes with the controlling enzyme of arginine synthesis, N-acetyl-L-glutamate kinase (NAGK) in a 2-oxoglutarate- and ATP/ADP-dependent manner. Fusing NAGK and PII proteins to either CFP or YFP yielded a FRET sensor that specifically responded to 2-oxoglutarate. The impact of the fluorescent tags on PII and NAGK was evaluated by enzyme assays, surface plasmon resonance spectroscopy and isothermal calorimetric experiments. The developed FRET sensor provides real-time data on PII - NAGK interaction and its modulation by the effector molecules ATP, ADP and 2-oxoglutarate in vitro. Additionally to its utility to monitor 2-oxoglutarate levels, the FRET assay provided novel insights into PII - NAGK complex formation: (i) It revealed the formation of an encounter-complex between PII and NAGK, which holds the proteins in proximity even in the presence of inhibitors of complex formation; (ii) It revealed that the PII T-loop residue Ser49 is neither essential for complex formation with NAGK nor for activation of the enzyme but necessary to form a stable complex and efficiently relieve NAGK from arginine inhibition; (iii) It showed that arginine stabilizes the NAGK hexamer and stimulates PII - NAGK interaction.
YBX1 Is a Modulator of MIA/CD-RAP-Dependent Chondrogenesis
2013-12-12

MIA/CD-RAP is a small, secreted protein involved in cartilage differentiation and melanoma progression. We recently revealed that p54(nrb) acts as a mediator of MIA/CD-RAP action to promote chondrogenesis and the progression of malignant melanoma. As the molecular mechanism of MIA/CD-RAP action in cartilage has not been defined in detail until now, we aimed to understand the regulation of p54(nrb) transcription in chondrogenesis. We concentrated on the previously described MIA/CD-RAP-dependent regulatory region in the p54(nrb) promoter and characterized the transcriptional regulation of p54(nrb) by MIA/CD-RAP in cartilage. A series of truncated p54(nrb) promoter constructs and mutagenesis analysis revealed that the transcription factor YBX1, which has not been investigated in chondrogenesis thus far, is the mediator of MIA/CD-RAP dependent activation of p54(nrb) transcription. A systematic analysis of genes carrying this binding site in their promoter region revealed further potential MIA/CD-RAP-regulated genes that have been implicated in cartilage differentiation. In summary, we described the effects of MIA/CD-RAP on transcriptional regulation in chondrocytes. Understanding the regulation of p54(nrb) via YBX1 contributes to the understanding of chondrogenesis. Uncovering new downstream effectors that function via the activation of YBX1 supports the important role of MIA/CD-RAP in these processes.
SwiftX-ray and ultraviolet observations of the shortest orbital period double-degenerate system RX J0806.3+1527 (HM Cnc)
2013-12-12

The system RX J0806.3+1527 (HM Cnc) is a pulsating X-ray source with 100 per\\ncent modulation on a period of 321.5 s (5.4 min). This period reflects the\\norbital motion of a close binary consisting of two interacting white dwarfs.\\nHere we present a series of simultaneous X-ray (0.2-10 keV) and\\nnear-ultraviolet (2600 angstrom and 1928 angstrom) observations that were\\ncarried out with the Swift satellite. In the near-ultraviolet, the counterpart\\nof RX J0806.3+1527 was detected at flux densities consistent with a blackbody\\nwith temperature 27E+3 K. We found that the emission at 2600 angstrom is\\nmodulated at the 321.5-s period with the peak ahead of the X-ray one by 0.28\\ncycles and is coincident within 0.05 cycles with the optical. This phase-shift\\nmeasurement confirms that the X-ray hot spot (located on the primary white\\ndwarf) is at about 80-100 degrees from the direction that connects the two\\nwhite dwarfs. Albeit at lower significance, the 321.5-s signature is present\\nalso in the 1928-angstrom data; at this wavelength, however, the pulse peak is\\nbetter aligned with that observed at X-rays. We use the constraints on the\\nsource luminosity and the geometry of the emitting regions to discuss the\\nmerits and limits of the main models for RX J0806.3+1527.\\n
Haemodialysis impairs clopidogrel but not aspirin responsiveness in patients with end-stage renal disease
2013-12-12

Summary Dual antiplatelet therapy (DAPT) with aspirin (ASA) and clopidogrel (Clp) is the standard treatment to reduce ischaemic coronary events, but in patients with end-stage renal disease (ESRD) the efficacy of Clp remains unclear. Patients with ESRD are at higher risk for coronary artery disease (CAD) and also their post-interventional outcome is worse compared to patients with normal renal function. Little is known about the influence of haemodialysis (HD) on ASA and Clp responsiveness. To assess the effect of HD on ASA- and Clp-responsiveness in patients with documented CAD and ESRD, 31 patients with ESRD (mean age 66.5 ± 1.8 years, 23 male ) on DAPT were evaluated for their ASA and Clp responsiveness with the Verify Now System (Accumetrics Inc.) We measured the antiplatelet effect in all ESRD patients at three time points: T1: just before HD; T2: directly after HD; T3: steady state on a HD free day one week after T1. In our study at baseline 10 (32.3%) patients were ASA-low responder (ASA-LR) and 14 (45.2%) patients Clp-low responder (Clp-LR). There was a significant difference in the PRU values before ( T1) and immediately after HD (T2) [PRU T1=234 (169; 274) vs PRUT2= 247 (199; 278); pT1,2=0.036; ]. Results were shown as median ARU T1 (25th, 75th percentile) or median PRU T1 (25th, 75th percentile). Hence HD seems to impair responsiveness to Clp, resulting in an increase of 6.5 % Clp-LR. No significant differences in the ARU values at the different time-points were found.
Engineering of a bio-functionalized hybrid off-the-shelf heart valve
2013-12-13

Currently available heart valve replacements are limited in long-term performance or fail due to leaflet thickening, lack of growth or remodeling potential. In order to address these issues, it is necessary to mimic multiple factors of the native valvular extracellular matrix (ECM) such as architecture, mechanical behavior and biochemical signals. Here, we successfully generated an electrospun PEGdma-PLA scaffold adapted to the structure and mechanical properties of native valve leaflets. Valvular interstitial cells (VICs) and valvular endothelial cells (VECs) were seeded on the scaffold and when cultured under physiological conditions in a bioreactor, the construct performed like a native leaflet. Atomic force microscopy (AFM) was employed to obtain detailed mechanical information from the leaflets, which enabled the first layer-specific measurement of the Young's modulus. Interestingly, spongiosa stiffness was much lower compared to the fibrosa and ventricularis. Moreover, investigations into human fetal heart valve development identified collagen type I and versican as important structural proteins. As a proof of principle, these proteins were introduced to the scaffold, demonstrating the ability to bio-functionalize the hybrid valve based on natures' blueprint.
What Is an Emotion? Musil’s Adverbial Theory
2013-12-13

What is an Emotion? Musil's Adverbial Theory Sabine Döring Sabine Döring Eberhard Karls Universität, Tübingen Search for other works by this author on: Oxford Academic PubMed Google Scholar The Monist, Volume 97, Issue 1, 1 January 2014, Pages 47–65, https://doi.org/10.5840/monist20149714 Published: 24 November 2014
Changes in peptidergic neurotransmission during postoperative ileus in rat circular jejunal muscle
2013-12-13

Abstract Background Our aim was to explore unknown changes in neurotransmission with vasoactive intestinal peptide ( VIP ) and Substance P (Sub P) during postoperative ileus ( POI ). Methods Contractile activity of rat circular jejunal muscle strips was studied in five groups (n = 6/group): Naïve controls, sham controls 12 h and 3 days after laparotomy, and rats 12 h, 3 days after induction of POI . Dose‐responses to VIP (10 −10 –10 −7 M), Sub P (3 × 10 −10 –3 × 10 −7 M), and electrical field stimulation ( EFS , to study endogenous release of neurotransmitters) were studied with different antagonists. Intestinal transit, inflammatory cells and immunoreactivity for VIP and Sub P were investigated in the bowel wall and cellular Finkel osteo sarcoma expression was determined in vagal afferent and efferent nuclei of the brainstem. Key Results Postoperative ileus characterized by delayed intestinal transit and intramural inflammation was associated with an increased inhibitory effect of VIP on contractile activity. A biphasic impact was observed for Sub P with a decrease in its excitatory potential on contractility at 12 h, followed by a later increase 3 days postoperatively. Inhibitory response to EFS was increased, whereas the excitatory response decreased in ileus animals. VIP expression was increased in all postoperative animals while only animals 3 days after ileus induction showed increased Sub P expression in the myenteric plexus. These changes were associated with an activation of afferent but not efferent vagal nuclei in the brain stem. Conclusions &amp; Inferences Specific, time‐dependent changes in peptidergic neurotransmission with VIP and Sub P occur during POI that are associated with vagal afferent activation, but are independent of the activation of efferent vagal pathways.
Two Small (p)ppGpp Synthases in Staphylococcus aureus Mediate Tolerance against Cell Envelope Stress Conditions
2013-12-14

ABSTRACT The stringent response is a conserved global regulatory mechanism that is related to the synthesis of (p)ppGpp nucleotides. Gram-positive bacteria, such as Staphylococcus aureus , possess three (p)ppGpp synthases: the bifunctional RSH (RelA/SpoT homolog) protein, which consists of a (p)ppGpp synthase and a (p)ppGpp hydrolase domain, and two truncated (p)ppGpp synthases, designated RelP and RelQ. Here, we characterized these two small (p)ppGpp synthases. Biochemical analyses of purified proteins and in vivo studies revealed a stronger synthetic activity for RelP than for RelQ. However, both enzymes prefer GDP over GTP as the pyrophosphate recipient to synthesize ppGpp. Each of the enzymes was shown to be responsible for the essentiality of the (p)ppGpp hydrolase domain of the RSH protein. The staphylococcal RSH-hydrolase is an efficient enzyme that prevents the toxic accumulation of (p)ppGpp. Expression of (p)ppGpp synthases in a hydrolase-negative background leads not only to growth arrest but also to cell death. Transcriptional analyses showed that relP and relQ are strongly induced upon vancomycin and ampicillin treatments. Accordingly, mutants lacking relP and relQ showed a significantly reduced survival rate upon treatments with cell wall-active antibiotics. Thus, RelP and RelQ are active (p)ppGpp synthases in S. aureus that are induced under cell envelope stress to mediate tolerance against these conditions.
The ROS‐induced cytotoxicity of ascorbate is attenuated by hypoxia and HIF‐1alpha in the NCI60 cancer cell lines
2013-12-14

Abstract Intravenous application of high‐dose ascorbate is used in complementary palliative medicine to treat cancer patients. Pharmacological doses of ascorbate in the mM range induce cytotoxicity in cancer cells mediated by reactive oxygen species ( ROS ), namely hydrogen peroxide and ascorbyl radicals. However, little is known about intrinsic or extrinsic factors modulating this ascorbate‐mediated cytotoxicity. Under normoxia and hypoxia, ascorbate IC 50 values were determined on the NCI 60 cancer cells. The cell cycle, the influence of cobalt chloride‐induced hypoxia‐inducible factor‐1α ( HIF ‐1α) and the glucose transporter 1 ( GLUT ‐1) expression (a pro‐survival HIF ‐1α‐downstream‐target) were analysed after ascorbate exposure under normoxic and hypoxic conditions. The amount of ascorbyl radicals increased with rising serum concentrations. Hypoxia (0.1% O 2 ) globally increased the IC 50 of ascorbate in the 60 cancer cell lines from 4.5 ± 3.6 mM to 10.1 ± 5.9 mM (2.2‐fold increase, P &lt; 0.001, Mann–Whitney t ‐test), thus inducing cellular resistance towards ascorbate. This ascorbate resistance depended on HIF ‐1α‐signalling, but did not correlate with cell line‐specific expression of the ascorbate transporter GLUT ‐1. However, under normoxic and hypoxic conditions, ascorbate treatment at the individual IC 50 reduced the expression of GLUT ‐1 in the cancer cells. Our data show a ROS ‐induced, HIF ‐1α‐ and O 2 ‐dependent cytotoxicity of ascorbate on 60 different cancer cells. This suggests that for clinical application, cancer patients should additionally be oxygenized to increase the cytotoxic efficacy of ascorbate.
Abstract PD6-7: The prognostic relevance of disseminated tumor cells (DTC) form the bone marrow (BM) in different molecular subtypes of primary breast cancer (PBC) patients
2013-12-15

Abstract Background: The presence of disseminated tumor cells (DTC) in the bone marrow (BM) of primary breast cancer (PBC) patients is associated with a worsened prognosis. This is the largest single-center study that determines the impact of DTC on disease free (DFS) and overall survival and compares it to predefined molecular subtypes of PBC. Methods: BM aspirates were collected from patients that underwent surgery for PBC at Tuebingen University Hospital, Germany between 01/2001 and 01/2013. DTC were identified by immunocytochemistry (pancytokeratin antibody A45/B3) and cytomorphology. Patients were divided into three subgroups based on immunohistochemical staining of the primary tumor: (1) hormone receptor-positive/HER2-negative (HR+/HER2-), (2) HER2-positive (HER2+), and (3) HR-negative/HER2-negative (HR-/HER2-) patients. The DTC-status was compared to other prognostic factors by use of the chi-squared test and survival was analyzed in an univariate (log-rank test) and multivariate analysis (cox regression). Results: 3,141 patients were available for this retrospective analysis. Of these 803 (26%) were DTC-positive. DTC-positivity was associated with larger tumors (p&amp;lt;0.001), positive lymph nodes (p = 0.001), ER-negative (p = 0.016) and PR-negative (p&amp;lt;0.001) patients. DTC-positive patients were at an increased risk of death (median OS of DTC- vs. DTC+ patients: n. r. (not reached) vs. 115 (95% CI: 113-118) months, p = 0.004) and disease relapse (median DFS was n. r. in either groups, p&amp;lt;0.001). Independent factors for OS / DFS were DTC-status, menopausal-status, tumor size, nodal-status, ER-status and PR-status / DTC-status, tumor size, nodal-status and ER-status. In the subgroup analysis (median OS was n. r. in either groups), the DTC-status had a significant impact on OS only within the HR+/HER2- subgroup (p = 0.004) and on DFS in the HR+/HER2- (p = 0.005) and the HER2+ subgroup (p&amp;lt;0.001). Conclusion: This study confirms the strong and independent prognostic value of DTC-determination in primary breast cancer patients. With respect to analysis of different molecular subtypes, the DTC-status was found to be of prognostic significance especially in HR+/HER2- patients. The DTC-status might help to identify HR+/HER2- patients that are at an increased risk of death or disease relapse and thus in need for an aggressive adjuvant treatment. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD6-7.
Abstract P6-06-32: 4EVER: Does mTOR inhibition have a major clinical impact on bone health in postmenopausal women with hormone receptor positive (HR+) locally advanced breast cancer treated with everolimus (EVE) in combination with exemestane (EXE)?
2013-12-15

Abstract Introduction: BOLERO-2, a multi-national, double-blind, placebo-controlled, phase 3 study in postmenopausal women with HR+, HER2- advanced breast cancer (BC) progressing after non-steroidal aromatase inhibitors (NSAI), showed significant benefit in PFS with the addition of the mTOR inhibitor EVE to EXE compared to EXE alone (Baselga J 2012). The BOLERO-2 bone sub study indicated an influence of EVE on bone health after 6 and 12 weeks of treatment (Gnant M 2012). To further investigate the long term influence of mTOR inhibition on bone health, we initiated the phase IIIb, multi-center, open label study 4EVER for postmenopausal women with HR+ locally advanced or metastatic breast cancer treated with EVE +EXE. The primary endpoint is the overall response rate (ORR) after 6 months. Secondary endpoints include progression free survival after 6 and 12 months, ORR after 12 months, overall survival, quality of life, health utilities and health care resources. The exploratory objectives focus amongst others on the assessment of biomarkers of bone turnover. Methods: Main inclusion criteria were postmenopausal women with metastatic or locally advanced, ER+, HER2- breast cancer refractory to NSAI. Markers of bone turnover (P-I-NP, CTX, OPG, RANKL, vitamin D, FSH and estradiol) are being assessed at baseline and after 4, 12 and 24 weeks on treatment. Results: Baseline characteristics: 334 postmenopausal patients were screened and 297 were enrolled in 5 months. The hormone receptor assessment was performed in 71.0% from primary tumor and in 29% from the metastases (ER+/PgR+ 77.5%, ER+/PgR- 21.5%). The mean time since initial diagnosis was 9.2 years. Mean time since first recurrence/ metastasis was 48.1 months and mean time since most recent recurrence / metastasis 2.4 months. The stage at primary diagnosis was M0 74.2% and M1 22.0%. 68.7% of the patients had bone lesions. Most recent antineoplastic medications were in the adjuvant (24.8%), neoadjuvant (1.1%) and palliative setting (71.0%). 25.6% of the patients had one, 16.4% two and 57.9% three and more prior therapies in metastatic setting. The results of the baseline bone and hormone maker analysis for baseline and after 4, 12 and 24 weeks on treatment will be presented. Conclusion: This exploratory bone study will provide further insights into the influence of mTOR inhibition on bone turnover and overall bone health in women with advanced breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-32.