julilili42/papers huggingface dataset:
Peptide‐Based 2‐Aminophenylamide Probes for Targeting Endogenous Class I Histone Deacetylase Complexes
2019-07-04

Abstract Lysine deacetylases or histone deacetylases (HDACs) remove acetylation markers from numerous cellular proteins, thereby regulating their function and activity. Recently established peptide probes containing the HDAC‐trapping amino acid α‐aminosuberic acid ω‐hydroxamate (AsuHd) have been used to investigate the compositions of HDAC complexes in a site‐specific manner. Here we report the new HDAC‐trapping amino acid 2‐amino‐8‐[(2‐aminophenyl)amino]‐8‐oxooctanoic acid (AsuApa) and the utility of AsuApa‐containing probes for HDAC complex profiling on a proteome‐wide scale. Unlike AsuHd‐containing probes, AsuApa enriched only HDACs 1, 2, and 3 efficiently and was the most potent probe tested for capturing the last of these. These findings indicate that the inherent specificity of reported small‐molecule pimelic diphenylamide HDAC inhibitors is preserved in AsuApa and that this HDAC‐trapping amino acid represents a potent tool for investigating class I HDAC complexes.
The flagellar substrate specificity switch protein FlhB assembles onto the extra-membrane export gate to regulate type three secretion
2019-07-04

Abstract Export of proteins through type three secretion systems (T3SS) is critical for motility and virulence of many major bacterial pathogens. Proteins are transported through an export gate complex consisting of three proteins (FliPQR in flagellar systems, SctRST in virulence systems) that were initially annotated as membrane proteins, but which we have recently shown assemble into an extra-membranous helical assembly. A fourth putative membrane protein (FlhB/SctU) is essential to the export process, and also functions to “switch” secretion substrate specificity once the growing hook/needle structures reach their determined length. Here we present the structure of an export gate containing the switch protein from a Vibrio polar flagellar system at 3.2 Å resolution by cryo-electron microscopy. The structure reveals that the FlhB/SctU further extends the helical export gate assembly with its four putative transmembrane helices adopting an out-of-membrane location, wrapped around the other export gate components at the base of the structure. The unusual topology of the switch protein helices creates a loop that wraps around the bottom of the closed export gate complex. Structure-informed mutagenesis suggests that this loop is critical in gating secretion and we propose that a series of conformational changes in the type 3 secretion system trigger opening of the export gate through the interactions between FlhB/SctU and FliPQR/SctRST.
Loss of Historical Phonetic Contrast Across the Lifespan: Articulatory, Lexical, and Social Effects on Sound Change in Swabian
2019-07-04

This chapter explores the extent to which phonetic environment, lexical frequency, and social factors interact and incite or impede sound change over the lifespan of the individual. The corpus consists of sociolinguistic interviews with 20 panel speakers of Swabian, an Alemannic dialect spoken in southwestern Germany, from two different communities, Stuttgart and Schwäbisch Gmünd, first recorded in 1982 and again in 2017. We investigate the modern standard German diphthong [ai] which evolved from two different Middle High German (MHG) phonemes, /i:/ and /ei/. We use generalised additive mixed-effect models to investigate to what extent F1/F2 trajectories in the vowel space differ in lemmata originating from the two MHG phonemes based on the Total Euclidean Distance Squared (TEDS). In addition to voicing effects, we find that an interaction between community, lexical frequency, and indexicalities of Swabian identity affects the degree to which the two diphthongs are merging, or at least becoming more similar to one another, within the lifespan of one generation. By analysing intra-speaker trajectories, we show how sound change is governed by the intricate interplay between structural factors and individual speaker notions of language ideology, social meaning, and dialect identity.
Building lattices and zeta functions
2019-07-04

Abstract We give a Lefschetz formula for tree lattices and apply it to geometric zeta functions. We further generalize Bass’s approach to Ihara zeta functions to the higher-dimensional case of a building.
Development of an Adapted Model for Decision-Making to Improve Reasoning and Risk Assessment in an Emergency Team: A Prospective Simulation Study
2019-07-04

Background and Objectives: Medical staff is rarely trained in structured decision-making, relying instead on intuition without due consideration for the associated pros and cons. Materials and Methods: We adopted a model for decision-making to improve reasoning and risk assessment and carried out a prospective simulation study using paramedic students in a three-year training program. We conducted a training session in which participants were lectured on decision-making using the FAR-BEK model (German abbreviation for facts, alternatives, risks, competence, decision, control), physiological processes in decision-making under stress, as well as medico-legal aspects for the comprehension and justification of medical decisions. We analyzed pre- and post-training scenarios to elucidate the influence of training on decision-making. Results: Twenty paramedic students, with a mean age of 22.0 ± 1.7 years, took part in the study. The question of whether decision aids can be applied, initially affirmed by 40% of participants, rose to 71.4% (p = 0.011) following our training. Confidence in decision-making increased on a 7-point Likert scale from 4.5 to 4.8 points (p &lt; 0.394). The reasoning behind the decisions rose from 5.3 to 5.6 points (p &lt; 0.081). Indication, options, and risks rose significantly, from 5.4 to 6.1 points (p = 0.045). Overall, our simulation training significantly increased the points of decision support taken into account (57.8% vs. 88.9%, p &lt; 0.001). Viewed individually, the largest increase of 180% was seen in risk assessment (33.3% vs. 93.3%, p &lt; 0.002). The second largest increase of 150% was seen in the question of one’s own permissions (26.7% vs. 66.7%, p &lt; 0.066). Also, the control increased (40.0% vs. 86.7%, p &lt; 0.021). Conclusions: With a brief training course, both the awareness and the implementation of a structured decision-making model in paramedic students can be significantly increased. Nevertheless, no definitive conclusions can be made with respect to the implementation of real patient care. The application of structured, standardized decision-making tools may need to be further consolidated in routine medical use.
A corpus of Schlieren photography of speech production - Potential to study aerodynamics of labial, nasal and vocalic processes
2019-07-04

This report presents a corpus of articulations recorded with Schlieren photography, a recording technique to visualize aeroflow dynamics for two purposes. First, as a means to investigate aerodynamic processes during speech production without any obstruction of the lips. Second, to provide material for lecturers of phonetics to illustrates these aerodynamic processes. Speech production was recorded with 10 kHz sampling rate for statistical video analyses (available at the Bavarian Archive for Speech Signals). Downsampled videos (500 Hz) were uplodad to a youtube channel for illustrative purposes.
Landscape Response to Lateral Advection in Convergent Orogens Over Geologic Time Scales
2019-07-05

Abstract Convergent orogens exhibit high elevations and relief, features characteristic of active rock uplift, the latter influencing normalized channel steepness ( K sn ). In systems with significant horizontal displacement, K sn values and interfluves are elevated over a region of tens of kilometers and gradually decline in the direction of rock advection. To evaluate potential relationships between elevated K sn , a gradual decline in interfluve elevation (i.e., tapered topography), and lateral advection, we integrated kinematic models that simulate advection over a midcrustal ramp with a 2‐D surface processes model. Varying convergence rate, bedrock erodibility, and ramp angle, we tracked topographic evolution over time. The process of advection through the region of active rock uplift above a midcrustal ramp is preserved in the geomorphic record through transient legacy landscapes characterized by (i) high‐relief, advection‐parallel interfluves, (ii) tapered topography, (iii) elevated and gradually declining K sn values, and (iv) higher K sn in trunk relative to tributary streams likely reflecting the influence of increased sediment flux, elevated interfluves, and changes in drainage area. The width of legacy landscapes provides a minimum constraint on the total lateral displacement, controlled by the duration of ramp activity and the rates of advection and erosion. The development of legacy landscapes is facilitated by spatial variations in flow convergence that occur in a 2‐D setting but are not captured in idealized 1‐D approaches. The presence of elevated K sn and high relief, advection‐parallel interfluves beyond the region of active rock uplift likely reflects the horizontal advection component inherent to convergent orogenic systems.
Starvation-Induced Differential Virotherapy Using an Oncolytic Measles Vaccine Virus
2019-07-05

Starvation sensitizes tumor cells to chemotherapy while protecting normal cells at the same time, a phenomenon defined as differential stress resistance. In this study, we analyzed if starvation would also increase the oncolytic potential of an oncolytic measles vaccine virus (MeV-GFP) while protecting normal cells against off-target lysis. Human colorectal carcinoma (CRC) cell lines as well as human normal colon cell lines were subjected to various starvation regimes and infected with MeV-GFP. The applied fasting regimes were either short-term (24 h pre-infection) or long-term (24 h pre- plus 96 h post-infection). Cell-killing features of (i) virotherapy, (ii) starvation, as well as (iii) the combination of both were analyzed by cell viability assays and virus growth curves. Remarkably, while long-term low-serum, standard glucose starvation potentiated the efficacy of MeV-mediated cell killing in CRC cells, it was found to be decreased in normal colon cells. Interestingly, viral replication of MeV-GFP in CRC cells was decreased in long-term-starved cells and increased after short-term low-glucose, low-serum starvation. In conclusion, starvation-based virotherapy has the potential to differentially enhance MeV-mediated oncolysis in the context of CRC cancer patients while protecting normal colon cells from unwanted off-target effects.
Dominance in Habitat Preference and Diurnal Explorative Behavior of the Weakly Electric Fish Apteronotus leptorhynchus
2019-07-05

Electrocommunication and -localization behaviors of weakly electric fish have been studied extensively in the lab, mostly by means of short-term observations on constrained fish. Far less is known about their behaviors in more natural-like settings, where fish are less constrained in space and time. We tracked individual fish in a population of fourteen brown ghost knifefish (<i>Apteronotus leptorhynchus</i>) housed in a large 2 m<sup>3</sup> indoor tank based on their electric organ discharges (EOD). The tank contained four different natural-like microhabitats (gravel, plants, isolated stones, stacked stones). In particular during the day individual fish showed preferences for specific habitats which provided appropriate shelter. Male fish with higher EOD frequencies spent more time in their preferred habitat during the day, moved more often between habitats during the night, and less often during the day in comparison to low-frequency males. Our data thus revealed a link between dominance indicated by higher EOD frequency, territoriality, and a more explorative personality in male <i>A. leptorhynchus</i>. In females, movement activity during both day and night correlated positively with EOD frequency. In the night, fish of either sex moved to another habitat after about 6 s on average. During the day, the average transition time was also very short at about 20 s. However, these activity phases were interrupted by phases of inactivity that lasted on average about 20 min during the day, but only 3 min in the night. The individual preference for daytime retreat sites did not reflect the frequent explorative movements at night.
The rate and spectrum of mosaic mutations during embryogenesis revealed by RNA sequencing of 49 tissues
2019-07-05

Abstract Background Mosaic mutations acquired during early embryogenesis can lead to severe early-onset genetic disorders and cancer predisposition, but are often undetectable in blood samples. The rate and mutational spectrum of embryonic mosaic mutations (EMMs) have only been studied in few tissues and their contribution to genetic disorders is unknown. Therefore, we investigated how frequent mosaic mutations occur during embryogenesis across all germ layers and tissues. Results Using RNA sequencing data from the Genotype-Tissue Expression (GTEx) cohort comprising 49 normal tissues and 570 individuals, we found that new-borns on average harbour 0.5 - 1 EMMs in the exome affecting multiple organs (1.3230 × 10 −8 per nucleotide per individual), a similar frequency as reported for germline de novo mutations. Our multi-tissue, multi-individual study design allowed us to distinguish mosaic mutations acquired during different stages of embryogenesis and adult life, as well as to provide insights into the rate and spectrum of mosaic mutations. We observed that EMMs are dominated by a mutational signature associated with spontaneous deamination of methylated cytosines and the number of cell divisions. After birth, cells continue to accumulate somatic mutations, which can lead to the development of cancer. Investigation of the mutational spectrum of the gastrointestinal tract revealed a mutational pattern associated with the food-borne carcinogen aflatoxin, a signature that has so far only been reported in liver cancer. Conclusion In summary, our multi-tissue, multi-individual study reveals a surprisingly high number of embryonic mosaic mutations in coding regions, implying novel hypotheses and diagnostic procedures for investigating genetic causes of disease and cancer predisposition.
The Influence of Foreland Structures on Hinterland Cooling: Evaluating the Drivers of Exhumation in the Eastern Bhutan Himalaya
2019-07-06

Abstract Understanding, and ideally quantifying, the relative roles of climatic and tectonic processes during orogenic exhumation is critical to resolving the dynamics of mountain building. However, vastly differing opinions regarding proposed drivers often complicate how thermochronometric ages are interpreted, particularly from the hinterland portions of thrust belts. Here we integrate three possible cross‐section geometries and kinematics along a transect through the eastern Bhutan Himalaya with a thermal model (Pecube‐D) to calculate the resulting thermal field and predict potential ages. We compare predicted ages to a suite of new and published cooling ages. Our results argue for ramp‐focused exhumation of the Main Central thrust from 16 to 14 Ma at shortening rates of 40–55 mm/year, followed by slower rates (25 mm/year) during the last 50 km of Main Central thrust displacement and growth of the Lesser Himalayan duplex from 14 to 11 Ma. Emplacement of frontal Lesser Himalayan thrust sheets occurred rapidly (55–70 mm/year) between ~11 and 9 Ma, followed by a decrease in shortening rates to ~10 mm/year during motion on the Main Boundary thrust. Modern shortening rates (17 mm/year) and out‐of‐sequence motion on the Main Boundary thrust from 0.5 Ma to present reproduce the young cooling ages near the Main Boundary thrust. We show that the dominant control on exhumation patterns in a fold‐thrust belt results from the evolution of ramps and emphasize that the geometry and kinematics of structures driving hinterland exhumation need to be evaluated with their linked foreland structures to ensure the viability of the proposed geometry, kinematics, and thus cooling history.
Charge transfer and electromagnetic enhancement processes revealed in the SERS and TERS of a CoPc thin film
2019-07-06

Abstract Phthalocyanines are frequently used as probing molecules in the field of single-molecule surface-enhanced Raman spectroscopy (SERS) and tip-enhanced Raman spectroscopy (TERS). In this work, we systematically compare the SERS and TERS spectra from a thin cobalt phthalocyanine (CoPc) film that is deposited on a Au film. The contributions from electromagnetic (EM), resonance, and charge-transfer enhancements are discussed. Radially and azimuthally polarized vector beams are used to investigate the influences of molecular orientation and the localized surface plasmon resonance (SPR). Furthermore, two different excitation wavelengths (636 and 532 nm) are used to study the resonant excitation effect as well as the involvement of the charge-transfer processes between CoPc and the Au substrate. It is shown that the Raman peaks of CoPc are mostly enhanced by 636 nm excitation through a combination of resonant excitation, high EM enhancement, and chemical enhancement via charge transfer from the metal to the molecule. At 532 nm excitation, however, the SERS and TERS spectra are dominated by photoluminescence, which originates from a photo-induced charge-transfer process from the optically excited molecule to the metal. The contributions of the different enhancement mechanisms explain the optical contrasts seen in the TERS images of Au nanodisks covered by the CoPc film. The insight achieved in this work will help to understand the optical contrast in sub- or single-molecule TERS imaging and apply SERS or TERS in the field of photocatalysis.
In Situ Single-Molecule AFM Investigation of Surface-Induced Fibrinogen Unfolding on Graphite
2019-07-06

Fibrinogen adsorption plays a key role in important biological processes, such as blood coagulation and foreign body reaction, which determine the biocompatibility of a material. Fibrinogen conformation on a surface is one of the main factors triggering these processes. Understanding the conformational dynamics of fibrinogen molecules adsorbed on solid surfaces is, therefore, of great interest in biomedicine and may contribute to the development of new biomaterials. In this work, unfolding of fibrinogen molecules adsorbed on a model surface (highly oriented pyrolytic graphite modified with an oligoglycine-hydrocarbon graphite modifier) is directly visualized using time-lapse atomic force microscopy. A gradual transformation of native-like fibrinogen molecules into fibrillar structures is observed at a timescale of several minutes. This transformation is accompanied by a decrease in molecular height from 4-5 to 1-2 nm. Independent unfolding of different fibrinogen domains is demonstrated. The obtained results provide a new, direct insight into the unfolding of individual fibrinogen molecules on a surface and give new opportunities for the development of graphite-based biosensors and biomaterials.
Gsα stimulation of mammalian adenylate cyclases regulated by their hexahelical membrane anchors
2019-07-06

Abstract Mammalian adenylate cyclases (ACs) are pseudoheterodimers with dissimilar hexahelical membrane-anchors, isoform-specifically conserved for more than half a billion years. We exchanged both membrane anchors of the AC isoform 2 by the isosteric quorum-sensing receptor from Vibrio , CqsS, which has a ligand, Cholera -Autoinducer-1 (CAI-1). In the chimera, AC activity was stimulated by Gsα, CAI-1 had no effect. Surprisingly, CAI-1 inhibited Gsα stimulation. We report that Gsα stimulation of human AC isoforms 2, 3, 5, and 9 expressed in Sf9 cells is inhibited by serum as is AC activity in membranes from rat brain cortex. AC2 activation by forskolin or forskolin/Gsα was similarly inhibited. Obviously, serum contains as yet unidentified factors affecting AC activity. The data establish a linkage in ACs, in which the membrane anchors, as receptors, transduce extracellular signals to the cytosolic catalytic dimer. A mechanistic three state model of AC regulation is presented compatible with all known regulatory inputs into mammalian ACs. The data allow designating the membrane anchors of mammalian ACs as orphan receptors and establish a new level of AC regulation.
Revisiting the regulation of the capsular polysaccharide biosynthesis gene cluster in Staphylococcus aureus
2019-07-08

Summary Capsular polysaccharide (CP) biosynthesis in Staphylococcus aureus is tightly controlled resulting in a heterogeneous phenotype within a population and CP being mainly detectable in nongrowing cells. Expression of the corresponding biosynthesis gene cluster is driven by one promoter element (P cap ). Here, we demonstrate that P cap contains a main SigB‐dependent promoter. The SigB consensus motif overlaps with a previously described inverted repeat (IR) that is crucial for cap expression. The essentiality of the IR is derived from this region acting as a SigB binding site rather than as an operator site for the proposed cap activators RbsR and MsaB. Furthermore, P cap contains an extensive upstream region harboring a weak SigA‐dependent promoter and binding sites for cap repressors such as SaeR, CodY and Rot. Heterogeneous CP synthesis is determined by SigB activity and repressor binding to the upstream region. SigB dependency and regulation by the upstream repressors are also sufficient to explain the temporal gene expression pattern at the transcriptional level. However, CP synthesis remains growth phase‐dependent even when transcription is rendered constitutive, suggesting additional posttranscriptional regulatory circuits. Thus, the interference of multiple repressors with SigB‐dependent promoter activity as well as post‐transcriptional mechanisms ensure the appropriate regulation of CP synthesis.
Soil Erosion Spatial Prediction using Digital Soil Mapping and RUSLE methods for Big Sioux River Watershed
2019-07-08

A recent conversion of the grasslands to cropland degrading the soil quality (SQ), and impacting the soil erosion and crop productivity in the West Corn Belt (WCB) of the USA. The current study was conducted to estimate the spatial distribution of soil erosion at Big Sioux River (BSR) watershed scale using the Geographical Information System (GIS)-enabled Revised Universal Soil Loss Equation (RUSLE). Spatial data such as weather, a digital elevation model (DEM), land use maps and soils were used for assessment of soil erosion was downloaded from the easily available online sources. Data showed that about 7% of grassland acreage reduced from 2008 (24%) to 2015 (17%), whereas, about 7.4% of cropland acreage increased from 2008 (64.6%) to 2015 (72%) in the BSR watershed. This grassland conversion to cropland increased the soil erosion (estimated using the RUSLE model) from 12.2 T ha−1 year−1 in 2008 to 14.8 T ha−1 year−1 in 2015. The present study concludes that grassland conversion to cropland in the BSR watershed increased the soil erosion, therefore, management practices essential to be applied to reduce the erosion risk and various other ecosystem services.
Digitalization in the Global South
2019-07-08

What are opportunities and risks of ICT in a global context from an ethical and interdisciplinary point of view? This TATuP special topic addresses often neglected issues, like unequal power relations, neo-colonialism, (digital) illiteracy, general barriers to access, or the gender digital divide.&#x0D; Editors: J. Heesen, L. Schelenz, K. Schopp and M. Pawelec
Do difficulty levels matter for graphical literacy? A performance assessment study with authentic graphs
2019-07-08

Malte Ringa* , Taiga Brahma & Christoph Randlerb a Chair of Economic Education, Eberhard Karls University, Tübingen, Germanyb Chair of Didactics of Biology, Eberhard Karls University, Tübingen, Germany