julilili42/papers huggingface dataset:
Endothelial C-Type Natriuretic Peptide Acts on Pericytes to Regulate Microcirculatory Flow and Blood Pressure
2018-04-06

Background: Peripheral vascular resistance has a major impact on arterial blood pressure levels. Endothelial C-type natriuretic peptide (CNP) participates in the local regulation of vascular tone, but the target cells remain controversial. The cGMP-producing guanylyl cyclase–B (GC-B) receptor for CNP is expressed in vascular smooth muscle cells (SMCs). However, whereas endothelial cell–specific CNP knockout mice are hypertensive, mice with deletion of GC-B in vascular SMCs have unaltered blood pressure. Methods: We analyzed whether the vasodilating response to CNP changes along the vascular tree, ie, whether the GC-B receptor is expressed in microvascular types of cells. Mice with a floxed GC-B ( Npr2 ) gene were interbred with Tie2-Cre or PDGF-Rβ-Cre ERT2 lines to develop mice lacking GC-B in endothelial cells or in precapillary arteriolar SMCs and capillary pericytes. Intravital microscopy, invasive and noninvasive hemodynamics, fluorescence energy transfer studies of pericyte cAMP levels in situ, and renal physiology were combined to dissect whether and how CNP/GC-B/cGMP signaling modulates microcirculatory tone and blood pressure. Results: Intravital microscopy studies revealed that the vasodilatatory effect of CNP increases toward small-diameter arterioles and capillaries. CNP consistently did not prevent endothelin-1–induced acute constrictions of proximal arterioles, but fully reversed endothelin effects in precapillary arterioles and capillaries. Here, the GC-B receptor is expressed both in endothelial and mural cells, ie, in pericytes. It is notable that the vasodilatatory effects of CNP were preserved in mice with endothelial GC-B deletion, but abolished in mice lacking GC-B in microcirculatory SMCs and pericytes. CNP, via GC-B/cGMP signaling, modulates 2 signaling cascades in pericytes: it activates cGMP-dependent protein kinase I to phosphorylate downstream targets such as the cytoskeleton-associated vasodilator-activated phosphoprotein, and it inhibits phosphodiesterase 3A, thereby enhancing pericyte cAMP levels. These pathways ultimately prevent endothelin-induced increases of pericyte calcium levels and pericyte contraction. Mice with deletion of GC-B in microcirculatory SMCs and pericytes have elevated peripheral resistance and chronic arterial hypertension without a change in renal function. Conclusions: Our studies indicate that endothelial CNP regulates distal arteriolar and capillary blood flow. CNP-induced GC-B/cGMP signaling in microvascular SMCs and pericytes is essential for the maintenance of normal microvascular resistance and blood pressure.
Estimates of late Cenozoic climate change relevant to Earth surface processes in tectonically active orogens
2018-04-06

Abstract. The denudation history of active orogens is often interpreted in the context of modern climate gradients. Here we address the validity of this approach and ask what are the spatial and temporal variations in palaeoclimate for a latitudinally diverse range of active orogens? We do this using high-resolution (T159, ca. 80 × 80 km at the Equator) palaeoclimate simulations from the ECHAM5 global atmospheric general circulation model and a statistical cluster analysis of climate over different orogens (Andes, Himalayas, SE Alaska, Pacific NW USA). Time periods and boundary conditions considered include the Pliocene (PLIO, ∼ 3 Ma), the Last Glacial Maximum (LGM, ∼ 21 ka), mid-Holocene (MH, ∼ 6 ka), and pre-industrial (PI, reference year 1850). The regional simulated climates of each orogen are described by means of cluster analyses based on the variability in precipitation, 2 m air temperature, the intra-annual amplitude of these values, and monsoonal wind speeds where appropriate. Results indicate the largest differences in the PI climate existed for the LGM and PLIO climates in the form of widespread cooling and reduced precipitation in the LGM and warming and enhanced precipitation during the PLIO. The LGM climate shows the largest deviation in annual precipitation from the PI climate and shows enhanced precipitation in the temperate Andes and coastal regions for both SE Alaska and the US Pacific Northwest. Furthermore, LGM precipitation is reduced in the western Himalayas and enhanced in the eastern Himalayas, resulting in a shift of the wettest regional climates eastward along the orogen. The cluster-analysis results also suggest more climatic variability across latitudes east of the Andes in the PLIO climate than in other time slice experiments conducted here. Taken together, these results highlight significant changes in late Cenozoic regional climatology over the last ∼ 3 Myr. Comparison of simulated climate with proxy-based reconstructions for the MH and LGM reveal satisfactory to good performance of the model in reproducing precipitation changes, although in some cases discrepancies between neighbouring proxy observations highlight contradictions between proxy observations themselves. Finally, we document regions where the largest magnitudes of late Cenozoic changes in precipitation and temperature occur and offer the highest potential for future observational studies that quantify the impact of climate change on denudation and weathering rates.
Tectonic and glacial contributions to focused exhumation in the Olympic Mountains, Washington, USA
2018-04-06

Tectonics and climate are major contributors to the topographic evolution of mountain ranges. Here, we investigate temporal variations in exhumation due to the onset of Pleistocene glaciation in the Olympic Mountains (Washington State, USA). We present 29 new apatite and zircon (U-Th)/He ages (AHe and ZHe), showing a decrease in ages toward the interior of the mountain range for both thermochronometric systems. Young AHe ages (<2 Ma) can be found on the western side and the interior of the mountain range. Thermokinematic modeling of sample cooling ages suggests, that ZHe ages can be explained by an ellipse-shaped exhumation pattern with lowest/highest rates of ∼0.25 and 0.9 km/m.y. These rates are interpreted as tectonically driven rock uplift, where the pattern of rates is governed by the shape of the subducted plate. However, the youngest AHe ages require a 50–150% increase in exhumation rates in the past 2–3 m.y. This increase in rates is contemporaneous with Pliocene-Pleistocene alpine glaciation of the orogen, indicating that tectonic rock uplift is perturbed by glacial erosion.
Low-Cost GRIN-Lens-Based Nephelometric Turbidity Sensing in the Range of 0.1–1000 NTU
2018-04-06

Turbidity sensing is very common in the control of drinking water. Furthermore, turbidity measurements are applied in the chemical (e.g., process monitoring), pharmaceutical (e.g., drug discovery), and food industries (e.g., the filtration of wine and beer). The most common measurement technique is nephelometric turbidimetry. A nephelometer is a device for measuring the amount of scattered light of suspended particles in a liquid by using a light source and a light detector orientated in 90° to each other. Commercially available nephelometers cost usually—depending on the measurable range, reliability, and precision—thousands of euros. In contrast, our new developed GRIN-lens-based nephelometer, called GRINephy, combines low costs with excellent reproducibility and precision, even at very low turbidity levels, which is achieved by its ability to rotate the sample. Thereby, many cuvette positions can be measured, which results in a more precise average value for the turbidity calculated by an algorithm, which also eliminates errors caused by scratches and contaminations on the cuvettes. With our compact and cheap Arduino-based sensor, we are able to measure in the range of 0.1–1000 NTU and confirm the ISO 7027-1:2016 for low turbidity values.
Sternal Reconstruction with the Omental Flap—Acute and Late Complications, Predictors of Mortality, and Quality of Life
2018-04-06

Background The omental flap is a reliable flap for the coverage of sternal defects. However, little is known about the predictors of mortality and the long-term outcome in such patients. Methods We, therefore, performed a retrospective study from 2002 to 2013, including all patients who underwent sternal reconstruction with the omental flap. Results A total of 50 patients were identified and mean follow-up was 3.8 years. Patient data was collected from the charts and 14 patients were available for telephone interviews. The majority of patients suffered from deep sternal wound infections. There was no complete flap loss and an overall success rate was 96%. In-hospital mortality was 14% and overall survival over follow-up was 50%. Significant predictors of mortality were age &gt; 65, American Society of Anesthesiologists' status, defect size, prolonged ventilation, and the need for tracheotomy. Postoperative quality of life was reduced compared with other cohorts, especially with regard to bodily function. Pain was also a major problem for most patients along with herniation. Conclusion The omental flap is a safe option even in patients with severe comorbidities. However, based on the data in this study, we would recommend the omental flap as a reserve option rather than first-line treatment for sternal defects.
d-Amino Acids Are Exuded by Arabidopsis thaliana Roots to the Rhizosphere
2018-04-07

Proteinogenic l-amino acids (l-AAs) are essential in all kingdoms as building blocks of proteins. Their d-enantiomers are also known to fulfill important functions in microbes, fungi, and animals, but information about these molecules in plants is still sparse. Previously, it was shown that d-amino acids (d-AAs) are taken up and utilized by plants, but their ways to reduce excessive amounts of them still remained unclear. Analyses of plant d-AA content after d-Ala and d-Glu feeding opened the question if exudation of d-AAs into the rhizosphere takes place and plays a role in the reduction of d-AA content in plants. The exudation of d-Ala and d-Glu could be confirmed by amino acid analyses of growth media from plants treated with these d-AAs. Further tests revealed that other d-AAs were also secreted. Nevertheless, treatments with d-Ala and d-Glu showed that plants are still able to reduce their contents within the plant without exudation. Further exudation experiments with transport inhibitors revealed that d-AA root exudation is rather passive and comparable to the secretion of l-AAs. Altogether, these observations argued against a dominant role of exudation in the regulation of plant d-AA content, but may influence the composition of the rhizosphere.
Classical density functional theory meets Monte-Carlo simulations
2018-04-08

Typically the quality of an approximate density functional is evaluated by a direct comparison of its predictions in a given test case to exact data obtained by computer simulations. An important example for such an approach is the test of equilibrium structure of a simple fluid as measured by the pair distribution function g(r) or the cavity correlation function y(r). However, the combination of exact density profiles and the analytical structure of density functional theory allows one to determine and potentially improve the quality of a functional in a more sophisticatedway.
Selective Genetic Overlap Between Amyotrophic Lateral Sclerosis and Diseases of the Frontotemporal Dementia Spectrum
2018-04-09

This study found novel genetic overlap between ALS and diseases of the FTD spectrum, that the MAPT H1 haplotype confers risk for ALS, and identified the mitophagy-associated, proapoptotic protein BNIP1 as an ALS risk gene. Together, these findings suggest that sporadic ALS may represent a selectively pleiotropic, polygenic disorder.
Transmission of breast cancer by a single multiorgan donor to 4 transplant recipients
2018-04-09

We report 4 cases of breast cancer transmission to transplant recipients from a single organ donor that occurred years after donation. The diagnosis of breast cancer was occult at the time of donation. All of the recipients developed a histologically similar type of breast cancer within 16 months to 6 years after transplantation. Three out of 4 recipients died as a result of widely metastasized disease. One of the recipients survived after transplant nephrectomy followed by cessation of immunosuppression and chemotherapy. This extraordinary case points out the often fatal consequences of donor-derived breast cancer and suggests that removal of the donor organ and restoration of immunity can induce complete remission.
Blade and bladelet production at Hohle Fels Cave, AH IV in the Swabian Jura and its importance for characterizing the technological variability of the Aurignacian in Central Europe
2018-04-09

Hohle Fels Cave in the Ach Valley of Southwestern Germany exhibits an Aurignacian sequence of 1 m thickness within geological horizons (GH) 6-8. The deposition of the layers took place during mild and cold phases between at least 42 ka (GI 10) and 36 ka calBP (GI 7). We present below a technological study of blade and bladelet production from AH IV (GH 7) at Hohle Fels. Our analyses show that blade manufacture is relatively constant, while bladelet production displays a high degree of variability in order to obtain different blanks. Knappers used a variety of burins as cores to produce fine bladelets. The results reveal a new variant of the Aurignacian in the Swabian Jura primarily characterized by the production of bladelets and microliths from burin-cores. The artefacts from the Swabian Aurignacian are technologically and functionally more diverse than earlier studies of the Geißenklösterle and Vogelherd sequences have suggested. The technological analyses presented here challenge the claim that the typo-chronological system from Southwestern Europe can be applied to the Central European Aurignacian. Instead, we emphasize the impact of technological and functional variables within the Aurignacian of the Swabian Jura.
Trivalent Rare-Earth-Metal Bis(trimethylsilyl)amide Halide Complexes by Targeted Oxidations
2018-04-09

In contrast to previously applied salt metathesis protocols the targeted rare-earth-metal compounds Ln[N(SiMe<sub>3</sub>)<sub>2</sub>]<sub>2</sub>(halogenido) were accessed by oxidation of Ln(II) silylamide precursors. Treatment of Sm[N(SiMe<sub>3</sub>)<sub>3</sub>]<sub>2</sub>(thf)<sub>2</sub> with 0.5 equiv of C<sub>2</sub>Cl<sub>6</sub> or 0.25 equiv of TeBr<sub>4</sub> in thf and crystallization thereof gave [Sm{N(SiMe<sub>3</sub>)<sub>2</sub>}<sub>2</sub>(μ-X)(thf)]<sub>2</sub> (X = Cl, Br). A similar reaction/crystallization procedure performed with 0.5 equiv of 1,2-diiodoethane gave monomeric Sm[N(SiMe<sub>3</sub>)<sub>2</sub>]<sub>2</sub>I(thf)<sub>2</sub>. Switching to Yb[N(SiMe<sub>3</sub>)<sub>2</sub>]<sub>2</sub>(thf)<sub>2</sub>, the aforementioned oxidants generated monomeric five-coordinate complexes Yb[N(SiMe<sub>3</sub>)<sub>2</sub>]<sub>2</sub>X(thf)<sub>2</sub> (X = Cl, Br, I). The reaction of Eu[N(SiMe<sub>3</sub>)<sub>2</sub>]<sub>2</sub>(thf)<sub>2</sub> with 0.5 equiv of C<sub>2</sub>Cl<sub>6</sub> in thf yielded the separated ion pair [Eu{N(SiMe<sub>3</sub>)<sub>2</sub>}<sub>3</sub>Cl][(thf)<sub>5</sub>Eu(μ-Cl)<sub>2</sub>Eu(thf)<sub>5</sub>]. Performing the chlorination in n-hexane led to oxidation followed by rapid disproportionation into EuCl<sub>3</sub>(thf) <sub>x</sub> and Eu[N(SiMe<sub>3</sub>)<sub>2</sub>]<sub>3</sub>. The bromination reaction did not afford crystalline material, while the iodination gave crystals of divalent EuI<sub>2</sub>(thf)<sub>5</sub>. Use of trityl chloride (Ph<sub>3</sub>CCl) as the oxidant in thf accomplished the Eu(III) species [Eu{N(SiMe<sub>3</sub>)<sub>2</sub>}<sub>2</sub>(μ-Cl)(thf)]<sub>2</sub>. In situ oxidation of putative [Tm{N(SiMe<sub>3</sub>)<sub>2</sub>}<sub>2</sub>(thf) <sub>x</sub>] using 0.5 equiv of C<sub>2</sub>Cl<sub>6</sub> in thf followed by crystallization from n-hexane led to the formation of a mixture of [Tm{N(SiMe<sub>3</sub>)<sub>2</sub>}<sub>2</sub>(μ-Cl)(thf)]<sub>2</sub> and Tm[N(SiMe<sub>3</sub>)<sub>2</sub>]<sub>3</sub>. Switching the oxidant to 0.5 equiv of 1,2-diiodoethane and crystallizing from thf repeatedly afforded the bis-halogenated complex Tm[N(SiMe<sub>3</sub>)<sub>2</sub>]I<sub>2</sub>(thf)<sub>3</sub>.
Composite Respect for Animals Scale
2018-04-09

Abstract A valid and convenient method to measure nonhuman animal attitudes contributes to feasible survey studies and the evaluation of educational programs. There are established scales for measuring animal attitudes but only some have acceptable psychometric properties: others address only a small fraction of the constructs, and some are overly long. We therefore aimed to develop a short, practicable measurement of animal attitudes that contains the constructs developed previously. Two studies were conducted: in the first one, 127 items were subjected to an exploratory factor analysis, which extracted 51 items in 10 factors. The scale was reduced to 20 items retaining all of the initial constructs with 13 positive and 7 negative items, which were subjected to a confirmatory factor analysis in study 2. Correlations with personality, meat consumption, age, and gender provide evidence for validity. We suggest using this short, unidimensional Composite Respect for Animals Scale covering a broad construct.
Establishment of STUB1/ CHIP mutant induced pluripotent stem cells (iPSCs) from a patient with Gordon Holmes syndrome/SCAR16
2018-04-09

STUB1/CHIP is a central component of cellular protein homeostasis and interacts with key proteins involved in the pathogenesis of many neurodegenerative diseases. Here, we reprogrammed human skin fibroblasts from a 12-year-old male patient with recessive spinocerebellar ataxia type 16 (OMIM #615768), carrying compound heterozygous mutations (c.355C>T, c.880A>T) in STUB1. Genomic integrity of the iPSC line HIHCNi001-A without transgene integration and genomic aberration but with maintained disease-relevant mutations was proven by SNP array analysis and Sanger sequencing while pluripotency was verified by the expression of important pluripotency markers and the capacity to differentiate into cells of all three germ layers.
Wormhole potentials and throats from quasi-normal modes
2018-04-10

Exotic compact objects refer to a wide class of black hole alternatives or\\neffective models to describe phenomenologically quantum gravitational effects\\non the horizon scale. In this work we show how the knowledge of the\\nquasi-normal mode spectrum of non-rotating wormhole models can be used to\\nreconstruct the effective potential that appears in the perturbation equations.\\nFrom this it is further possible to obtain the parameters that characterize the\\nspecific wormhole model, which in this paper was chosen to be the one by Damour\\nand Solodukhin. We also address the question whether one can distinguish such\\ntype of wormholes from ultra compact stars, if only the quasi-normal mode\\nspectrum is known. We have proven that this is not possible by using the\\ntrapped modes only, but requires additional information.\\n The here presented inverse method is an extension of work that has previously\\nbeen developed and applied to the oscillation spectra of ultra compact stars\\nand gravastars. However, it is not limited to the study of exotic compact\\nobjects, but applicable to symmetric double barrier potentials that appear in\\none-dimensional wave equations. Therefore we think it can be of interest for\\nother fields too.\\n
Lexical frequency co-determines the speed-curvature relation in articulation
2018-04-10

The relation between speed and curvature provides a characterization of the spatio-temporal orchestration of kinematic movements. For hand movements, this relation has been reported to follow a power law with exponent -1/3. The same power law has been claimed to govern articulatory movements. We studied the functional form of speed as predicted by curvature using electromagnetic articulography, focusing on three sensors: the tongue tip, the tongue body, and the lower lip. Of specific interest to us was the question of whether the speed-curvature relation is modified by articulatory practice, gauged with words' frequencies of occurrence. Although analyses imposing linearity a priori indeed supported a power law, relaxation of this linearity assumption revealed that the effect of curvature on speed levels off substantially for lower values of curvature. A modification of the power law is proposed that takes this curvature into account. Furthermore, controlling statistically for number of phones and word duration, we observed that the speed-curvature function was further modulated by an interaction of lexical frequency by curvature, such that for increasing frequency, speed decreased slightly for low curvatures while it increased slightly for high curvatures. The modulation of the balance between speed and curvature by lexical frequency provides further evidence that the skill of articulation improves with practice on a word-to-word basis, and challenges theories of speech production.
Drinking Ethanol Has Few Acute Effects on CYP2C9, CYP2C19, NAT2, and P‐Glycoprotein Activities but Somewhat Inhibits CYP1A2, CYP2D6, and Intestinal CYP3A: So What?
2018-04-10

We quantified the effect of acute ethanol exposure (initial blood concentrations 0.7 g/L) on major drug metabolizing enzymes and p‐glycoprotein. Sixteen healthy Caucasians participated in a randomized crossover study with repeated administration of either vodka or water. Enzyme/transporter activity was assessed by a cocktail of probe substrates, including caffeine (CYP1A2/NAT2), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A), and digoxin (P‐glycoprotein). The ratio of AUC 0‐t of dextromethorphan for ethanol/water coadministration was 1.95 (90% confidence interval (CI) 1.48–2.58). The effect was strongest in individuals with a CYP2D6 genotype predicting high activity ( n = 7, ratio 2.66, 90% CI 1.65–4.27). Ethanol increased caffeine AUC 0‐t 1.38‐fold (90% CI 1.25–1.52) and reduced intestinal midazolam extraction 0.77‐fold (90% CI 0.69–0.86). The other probe drugs were not affected by ethanol. The results suggest that acute ethanol intake typically has no clinically important effect on the enzymes/transporters tested.
Beyond Histones: New Substrate Proteins of Lysine Deacetylases in Arabidopsis Nuclei
2018-04-10

The reversible acetylation of lysine residues is catalyzed by the antagonistic action of lysine acetyltransferases and deacetylases, which can be considered as master regulators of their substrate proteins. Lysine deacetylases, historically referred to as histone deacetylases, have profound functions in regulating stress defenses and development in plants. Lysine acetylation of the N-terminal histone tails promotes gene transcription and decondensation of chromatin, rendering the DNA more accessible to the transcription machinery. In plants, the classical lysine deacetylases from the RPD3/HDA1-family have thus far mainly been studied in the context of their deacetylating activities on histones, and their versatility in molecular activities is still largely unexplored. Here we discuss the potential impact of lysine acetylation on the recently identified nuclear substrate proteins of lysine deacetylases from the Arabidopsis RPD3/HDA1-family. Among the deacetylase substrate proteins, many interesting candidates involved in nuclear protein import, transcriptional regulation, and chromatin remodeling have been identified. These candidate proteins represent key starting points for unraveling new molecular functions of the Arabidopsis lysine deacetylases. Site-directed engineering of lysine acetylation sites on these target proteins might even represent a new approach for optimizing plant growth under climate change conditions.