julilili42/papers huggingface dataset:
KINESIN-12E regulates metaphase spindle flux and helps control spindle size in Arabidopsis
2020-11-17

Abstract The bipolar mitotic spindle is a highly conserved structure among eukaryotes that mediates chromosome alignment and segregation. Spindle assembly and size control are facilitated by force-generating microtubule-dependent motor proteins known as kinesins. In animals, kinesin-12 cooperates with kinesin-5 to produce outward-directed forces necessary for spindle assembly. In plants, the relevant molecular mechanisms for spindle formation are poorly defined. While an Arabidopsis thaliana kinesin-5 ortholog has been identified, the kinesin-12 ortholog in plants remains elusive. In this study, we provide experimental evidence for the function of Arabidopsis KINESIN-12E in spindle assembly. In kinesin-12e mutants, a delay in spindle assembly is accompanied by the reduction of spindle size, demonstrating that KINESIN-12E contributes to mitotic spindle architecture. Kinesin-12E localization is mitosis-stage specific, beginning with its perinuclear accumulation during prophase. Upon nuclear envelope breakdown, KINESIN-12E decorates subpopulations of microtubules in the spindle and becomes progressively enriched in the spindle midzone. Furthermore, during cytokinesis, KINESIN-12E shares its localization at the phragmoplast midzone with several functionally diversified Arabidopsis KINESIN-12 members. Changes in the kinetochore and in prophase and metaphase spindle dynamics occur in the absence of KINESIN-12E, suggest it might play an evolutionarily conserved role during spindle formation similar to its spindle-localized animal kinesin-12 orthologs.
Cysteine in cell culture media induces acidic IgG1 species by disrupting the disulfide bond network
2020-11-17

Abstract A high degree of charge heterogeneity is an unfavorable phenomenon commonly observed for therapeutic monoclonal antibodies (mAbs). Removal of these impurities during manufacturing often comes at the cost of impaired step yields. A wide spectrum of posttranslational and chemical modifications is known to modify mAb charge. However, a deeper understanding of underlying mechanisms triggering charged species would be beneficial for the control of mAb charge variants during bioprocessing. In this study, a comprehensive analytical investigation was carried out to define the root causes and mechanisms inducing acidic variants of an immunoglobulin G1‐derived mAb. Characterization of differently charged species by liquid chromatography–mass spectrometry revealed the reduction of disulfide bonds in acidic variants, which is followed by cysteinylation and glutathionylation of cysteines. Importantly, biophysical stability and integrity of the mAb are not affected. By in vitro incubation of the mAb with the reducing agent cysteine, disulfide bond degradation was directly linked to an increase of numerous acidic species. Modifying the concentrations of cysteine during the fermentation of various mAbs illustrated that redox potential is a critical aspect to consider during bioprocess development with respect to charge variant control.
Control of blood pressure in older patients with heart failure and the risk of mortality: a population-based prospective cohort study
2020-11-17

Abstract Background treatment goals for blood pressure (BP) lowering in older patients with heart failure (HF) are unclear. Objective to assess whether BP control &amp;lt; 140/90 mmHg is associated with a decreased risk of mortality in older HF patients. Design population-based prospective cohort study. Setting/subjects participants of the Berlin Initiative Study, a prospective cohort of community-dwelling older adults launched in 2009. Clinical information was obtained in face-to-face interviews and linked to administrative healthcare data. Methods Cox proportional hazards models estimated adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of cardiovascular death and all-cause mortality associated with normalised BP (systolic BP &amp;lt; 140 mmHg and diastolic BP &amp;lt; 90 mmHg) compared with non-normalised BP (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) in HF patients. The primary analysis considered only baseline BP (‘time-fixed’); an additional analysis updated BP during follow-up (‘time-dependent’). Results at baseline, 544 patients were diagnosed with HF and treated with antihypertensive drugs (mean age 82.8 years; 45.4% female). During a median follow-up of 7.5 years and compared with non-normalised BP, normalised BP was associated with similar risks of cardiovascular death (HR, 1.24; 95% CI, 0.84–1.85) and all-cause mortality (HR, 1.16; 95% CI, 0.89–1.51) in the time-fixed analysis but with increased risks of cardiovascular death (HR, 1.79; 95% CI, 1.23–2.61) and all-cause mortality (HR, 1.48; 95% CI, 1.15–1.90) in the time-dependent analysis. Conclusions BP control &amp;lt; 140/90 mmHg was not associated with a decreased risk of mortality in older HF patients. The increased risk in the time-dependent analysis requires further corroboration.
Numerical analysis for nematic electrolytes
2020-11-17

Abstract We consider a system of nonlinear PDEs modeling nematic electrolytes, and construct a dissipative solution with the help of its implementable, structure-inheriting and space–time discretization. Computational studies are performed to study the mutual effects of electric, elastic and viscous effects onto the molecules in a nematic electrolyte.
Modulating Effect of Ligand Charge on the Electronic Properties of 2Ni–2S Structures and Implications for Biological 2M–2S Sites
2020-11-17

Sulfur-bridged bimetallic 2M-2S type structures are essential cofactors that participate in biological long-range electron transport and metabolism. Metal-sulfur bond covalency is a decisive property for inner sphere (through-bond) type electron transfer that dominates in buried or hydrophobic protein environments. This work reports on a combined experimental and computational study of the effect of ligand charge on the electronic structure of a 2Ni-2S model site that adopts the biologically relevant <i>S</i> = <sup>1</sup>/<sub>2</sub> redox state. Starting out from an isostructural dinickel(1.5+)-dithiophenolate platform with sulfur-bridged tetrahedral Ni sites, η<sup>2</sup>:η<sup>2</sup>-μ-coordination of the <i>S</i> = <sup>1</sup>/<sub>2</sub> [2Ni-2S]<sup>+</sup> core to either a neutral π-system or strongly σ-donating cyclohexadienido renders its electronic structure substantially different. Density functional theory analysis corroborates pulse and continuous wave electron paramagnetic resonance data that associate co-ligand charge with the significant change in the mechanism and size of electron-<sup>31</sup>P nuclear spin hyperfine coupling to a phosphine reporter ligand at each nickel center. An increasing level of charge donation attenuates direct and through-bridge electronic coupling of the metal sites, resulting in a stronger electronic coupling of the 2Ni-2S core to its terminal phosphine donors. Drawing a connection to biological 2M-2S sites, our 2Ni-2S system indicates that a fine balance of intracore and core-protein electronic coupling is key to biological function for which the degree of charge donation by peripheral donors appears to be a significant parameter.
An Integrated Workflow for Enhanced Taxonomic and Functional Coverage of the Mouse Faecal Metaproteome
2020-11-17

Abstract Intestinal microbiota plays a key role in shaping host homeostasis by regulating metabolism, immune responses and behaviour. Its dysregulation has been associated with metabolic, immune and neuropsychiatric disorders and is accompanied by changes in bacterial metabolic regulation. Although proteomics is well suited for analysis of individual microbes, metaproteomics of faecal samples is challenging due to the physical structure of the sample, presence of contaminating host proteins and coexistence of hundreds of microorganisms. Furthermore, there is a lack of consensus regarding preparation of faecal samples, as well as downstream bioinformatic analyses following metaproteomics data acquisition. Here we assess sample preparation and data analysis strategies applied to mouse faeces in a typical mass spectrometry-based metaproteomic experiment. We show that subtle changes in sample preparation protocols may influence interpretation of biological findings. Two-step database search strategies led to significant underestimation of false positive protein identifications. Unipept software provided the highest sensitivity and specificity in taxonomic annotation of the identified peptides of unknown origin. Comparison of matching metaproteome and metagenome data revealed a positive correlation between protein and gene abundances. Notably, nearly all functional categories of detected protein groups were differentially abundant in the metaproteome compared to what would be expected from the metagenome, highlighting the need to perform metaproteomics when studying complex microbiome samples.
Threat-induced hippocampal connectivity fingerprints do not generalize to psychosocial stress
2020-11-17

Abstract Stress is an everyday experience and maladaptive responses play a crucial role in the etiology of affective disorders. Despite its ubiquity, the neural underpinnings of subjective stress experiences have not yet been elucidated, particularly at an individual level. In an important advance, Goldfarb et al. 1 showed recently that subjective stress and arousal levels in response to threatening stimuli were successfully predicted based on changes in hippocampal connectivity during the task using a machine learning approach. Crucially, stress responses were predicted by interpretable hippocampal connectivity networks, shedding new light on the role of the hippocampus in regulating stress reactivity 2 . However, the authors induced stress by displaying aversive pictures, while stress research often relies on the extensively validated Trier social stress task (TSST) 3 . The TSST incorporates crucial factors such as unpredictability of success and the social-evaluative threat of the stressor thereby eliciting cortisol responses more robustly compared to threatening images 4 . Towards generalization, cross validation within a sample as conducted by Goldfarb et al. 1 or independent replications are important steps, but the generalizability to different stressors allows to draw broader conclusions about the potential use of hippocampal connectivity to predict subjective stress 5 . Arguably, translating these findings to clinical applications would require a broad generalization of the results or the prediction algorithm to psychosocial stress. Here, we assessed the predictive performance of Goldfarb et al’s 1 algorithm for subjective stress in an independent sample using an MR adaption of the TSST 6,7 . In line with Goldfarb et al. 1 , we observed robust stress-induced changes in hippocampal connectivity. However, the spatial correlation of the changes in connectivity was low indicating little convergence across alleged stress paradigms. Critically, stress-induced changes of hippocampal connectivity were not robustly predictive of subjective stress across a multiverse of analyses based on connectivity changes. Collectively, this indicates that the generalizability of the reported stress connectivity fingerprint to other stressors is limited at best, suggesting that specific tasks might require tailored algorithms to robustly predict stress above chance levels.
Pre-exposure to Candida glabrata protects Galleria mellonella against subsequent lethal fungal infections
2020-11-17

Commensal fungi are an important part of human microbial community, among which <i>Candida albicans</i> and <i>Candida glabrata</i> are two common opportunistic pathogens. Unlike the high pathogenicity of <i>C. albicans, C. glabrata</i> is reported to show low pathogenicity to the host. Here, by using a <i>Galleria mellonella</i> infection model, we were able to confirm the much lower virulence of <i>C. glabrata</i> than <i>C. albicans</i>. Interestingly, pre-exposure to live <i>C. glabrata</i> (LCG) protects the larvae against subsequent various lethal fungal infections, including <i>C. albicans, Candida tropicalis,</i> and <i>Cryptococcus neoformans</i>. Inconsistently, heat-inactivated <i>C. glabrata</i> (HICG) pre-exposure can only protect against <i>C. albicans</i> or <i>C. tropicalis</i> re-infection, but not <i>C. neoformans</i>. Mechanistically, LCG or HICG pre-exposure enhanced the fungicidal activity of hemocytes against <i>C. albicans</i> or <i>C. tropicalis</i>. Meanwhile, LCG pre-exposure enhanced the humoral immunity by modulating the expression of fungal defending proteins in the cell-free hemolymph, which may contribute to the protection against <i>C. neoformans</i>. Together, this study suggests the important role of <i>C. glabrata</i> in enhancing host immunity, and demonstrates the great potential of <i>G. mellonella</i> model in studying the innate immune responses against infections.
Medical education in times of COVID-19: German students’ expectations – A cross-sectional study
2020-11-18

Background Since the COVID-19 pandemic has affected the education of medical students, medical faculties have faced the challenge of adapting instruction to digital platforms. Although medical students are willing to support pandemic response efforts, how the crisis will affect their medical training remains uncertain. Thus, in this study, we investigated the teaching- and learning-related stressors and expectations of medical students in Germany during the COVID-19 pandemic. Methods A cross-sectional survey was distributed online to undergraduate medical students at medical faculties in Germany. Students answered questions about COVID-19 and teaching (on a 7-point Likert scale from 0 (“not at all”) to 6 (“completely”)) and completed mental well-being measurements, including the State–Trait Anxiety Inventory (STAI), the Generalised Anxiety Disorder scale (GAD-7) and the Perceived Health Questionnaire (PHQ-9). Descriptive data analysis, a t -test and Pearson correlations were performed to process the data. Results Medical students felt well-informed about COVID-19 in general ( M = 5.64, SD = 1.28) and in the medical context ( M = 5.14, SD = 1.34) but significantly less informed about the pandemic in the academic context, M = 2.47, SD = 1.49, t (371) = 31.98, p &lt; .001. Their distress levels were high (STAI: M = 45.12, SD = 4.73) and significantly correlated with the academic context ( r p = .164, p &lt; .01) but not their private lives. Concerning how they were taught, they most often expected online lectures (91.7%) and live broadcasts (67.2%) and less often expected innovative digital teaching strategies, including serious games (17.3%) and virtual-reality exercises (16.7%). Discussion Medical students seem to be aware of the COVID-19 pandemic and its consequences for academic and healthcare contexts. They also seem to think that their teachers will enhance their digital competencies during the pandemic. Therefore, faculties of medicine need to rapidly and adequately digitalise their approaches to teaching.
Learning vocabulary and grammar from cross-situational statistics
2020-11-18

Across multiple situations, child and adult learners are sensitive to co-occurrences between individual words and their referents in the environment, which provide a means by which the ambiguity of word-world mappings may be resolved (Monaghan & Mattock, 2012; Scott & Fisher, 2012; Smith & Yu, 2008; Yu & Smith, 2007). In three studies, we tested whether cross-situational learning is sufficiently powerful to support simultaneous learning the referents for words from multiple grammatical categories, a more realistic reflection of more complex natural language learning situations. In Experiment 1, adult learners heard sentences comprising nouns, verbs, adjectives, and grammatical markers indicating subject and object roles, and viewed a dynamic scene to which the sentence referred. In Experiments 2 and 3, we further increased the uncertainty of the referents by presenting two scenes alongside each sentence. In all studies, we found that cross-situational statistical learning was sufficiently powerful to facilitate acquisition of both vocabulary and grammar from complex sentence-to-scene correspondences, simulating the situations that more closely resemble the challenge facing the language learner.
Minimizing the Trade-Off between Photocurrent and Photovoltage in Triple-Cation Mixed-Halide Perovskite Solar Cells
2020-11-18

Its lower bandgap makes formamidinium lead iodide (FAPbI3) a more suitable candidate for single-junction solar cells than pure methylammonium lead iodide (MAPbI3). However, its structural and thermodynamic stability is improved by introducing a significant amount of MA and bromide, both of which increase the bandgap and amplify trade-off between the photocurrent and photovoltage. Here, we simultaneously stabilized FAPbI3 into a cubic lattice and minimized the formation of photoinactive phases such as hexagonal FAPbI3 and PbI2 by introducing 5% MAPbBr3, as revealed by synchrotron X-ray scattering. We were able to stabilize the composition (FA0.95MA0.05Cs0.05)Pb(I0.95Br0.05)3, which exhibits a minimal trade-off between the photocurrent and photovoltage. This material shows low energetic disorder and improved charge-carrier dynamics as revealed by photothermal deflection spectroscopy (PDS) and transient absorption spectroscopy (TAS), respectively. This allowed the fabrication of operationally stable perovskite solar cells yielding reproducible efficiencies approaching 22%.
Protein Crystallization in the Presence of a Metastable Liquid–Liquid Phase Separation
2020-11-18

We study protein crystallization in solutions of human serum albumin (HSA) exhibiting a metastable liquid-liquid phase separation (LLPS) in the presence of trivalent salts. Specifically, we focus on the effects of dense liquid phases (DLPs) on the crystallization pathways. On the basis of the phase diagram, we choose two conditions around the LLPS binodal: one condition is located close to, but outside the LLPS region, resulting in protein clusters, but no macroscopic LLPS. Yet, a surface-enhanced unstable DLP layer is observed at the surface of the cuvette (wetting). The second condition, inside the LLPS binodal, leads to a macroscopic metastable DLP. The crystallization is followed by optical microscopy and small-angle X-ray and neutron scattering (SAXS/SANS) as well as by ultraviolet-visible spectroscopy to explore the role of LLPS. In no case evidence of nucleation inside the DLP is observed. SAXS and SANS show a monotonous growth of the crystals and a decrease of the overall material in the sample. We thus conclude that the existence of a metastable LLPS is not a sufficient condition for a two-step nucleation process. The DLP serves as a reservoir and crystal growth can be described by the Bergeron process, i.e., crystals grow directly into the dilute phase at the expense of the DLP. Furthermore, the crystallographic analysis of the resulting crystals shows that crystals with different morphology grown under different conditions share a similar crystal structure and that the metal ions create two bridging contacts within the unit cell and stabilize it.
Introducing platform surface interior angle (PSIA) and its role in flake formation, size and shape
2020-11-18

Four ways archaeologists have tried to gain insights into how flintknapping creates lithic variability are fracture mechanics, controlled experimentation, replication and attribute studies of lithic assemblages. Fracture mechanics has the advantage of drawing more directly on first principles derived from physics and material sciences, but its relevance to controlled experimentation, replication and lithic studies more generally has been limited. Controlled experiments have the advantage of being able to isolate and quantify the contribution of individual variables to knapping outcomes, and the results of these experiments have provided models of flake formation that when applied to the archaeological record of flintknapping have provided insights into past behavior. Here we develop a linkage between fracture mechanics and the results of previous controlled experiments to increase their combined explanatory and predictive power. We do this by documenting the influence of Herztian cone formation, a constant in fracture mechanics, on flake platforms. We find that the platform width is a function of the Hertzian cone constant angle and the geometry of the platform edge. This finding strengthens the foundation of one of the more influential models emerging from the controlled experiments. With additional work, this should make it possible to merge more of the experimental results into a more comprehensive model of flake formation.
Extreme Universe Space Observatory on a Super Pressure Balloon 1\\n calibration: from the laboratory to the desert
2020-11-18

The Extreme Universe Space Observatory on a Super Pressure Balloon 1\\n(EUSO-SPB1) instrument was launched out of Wanaka, New Zealand, by NASA in\\nApril, 2017 as a mission of opportunity. The detector was developed as part of\\nthe Joint Experimental Missions for the Extreme Universe Space Observatory\\n(JEM-EUSO) program toward a space-based ultra-high energy cosmic ray (UHECR)\\ntelescope with the main objective to make the first observation of UHECRs via\\nthe fluorescence technique from suborbital space. The EUSO-SPB1 instrument is a\\nrefractive telescope consisting of two 1m Fresnel lenses with a high-speed\\nUV camera at the focal plane. The camera has 2304 individual pixels capable of\\nsingle photoelectron counting with a time resolution of 2.5 s. A detailed\\nperformance study including calibration was done on ground. We separately\\nevaluated the properties of the Photo Detector Module (PDM) and the optical\\nsystem in the laboratory. An end-to-end test of the instrument was performed\\nduring a field campaign in the West Desert in Utah, USA at the Telescope Array\\n(TA) site in September 2016. The campaign lasted for 8 nights. In this article\\nwe present the results of the preflight laboratory and field tests. Based on\\nthe tests performed in the field, it was determined that EUSO-SPB1 has a field\\nof view of 11.1 and an absolute photo-detection efficiency of 10%. We\\nalso measured the light flux necessary to obtain a 50% trigger efficiency using\\nlaser beams. These measurements were crucial for us to perform an accurate post\\nflight event rate calculation to validate our cosmic ray search. Laser beams\\nwere also used to estimated the reconstruction angular resolution. Finally, we\\nperformed a flat field measurement in flight configuration at the launch site\\nprior to the launch providing a uniformity of the focal surface better than 6%.\\n