julilili42/papers huggingface dataset:
PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease
2020-03-03

Abstract Background: Progesterone receptor membrane component 1 (PGRMC1) is often elevated in cancers, and exists in alternative states of phosphorylation. A motif centered on PGRMC1 Y180 was evolutionarily acquired concurrently with the embryological gastrulation organizer that orchestrates vertebrate tissue differentiation.Results: Here, we show that mutagenic manipulation of PGRMC1 phosphorylation alters cell metabolism, genomic stability, and CpG methylation. Each of several mutants elicited distinct patterns of genomic CpG methylation. Mutation of S57A/Y180/S181A led to increased net hypermethylation, reminiscent of embryonic stem cells. Pathways enrichment analysis suggested modulation of processes related to animal cell differentiation status and tissue identity, as well as cell cycle control and ATM/ATR DNA damage repair regulation. We detected different genomic mutation rates in culture.Conclusions: A companion manuscript shows that these cell states dramatically affect protein abundances, cell and mitochondrial morphology, and glycolytic metabolism. We propose that PGRMC1 phosphorylation status modulates cellular plasticity mechanisms relevant to early embryological tissue differentiation.
Efficacy and Safety of Liraglutide 3.0 mg in Individuals With Overweight or Obesity and Type 2 Diabetes Treated With Basal Insulin: The SCALE Insulin Randomized Controlled Trial
2020-03-04

OBJECTIVE Most individuals with type 2 diabetes also have obesity, and treatment with some diabetes medications, including insulin, can cause further weight gain. No approved chronic weight management medications have been prospectively investigated in individuals with overweight or obesity and insulin-treated type 2 diabetes. The primary objective of this study was to assess the effect of liraglutide 3.0 mg versus placebo on weight loss in this population. RESEARCH DESIGN AND METHODS Satiety and Clinical Adiposity—Liraglutide Evidence (SCALE) Insulin was a 56-week, randomized, double-blind, placebo-controlled, multinational, multicenter trial in individuals with overweight or obesity and type 2 diabetes treated with basal insulin and ≤2 oral antidiabetic drugs. RESULTS Individuals were randomized to liraglutide 3.0 mg (n = 198) or placebo (n = 198), combined with intensive behavioral therapy (IBT). At 56 weeks, mean weight change was −5.8% for liraglutide 3.0 mg versus −1.5% with placebo (estimated treatment difference −4.3% [95% CI −5.5; −3.2]; P &amp;lt; 0.0001). With liraglutide 3.0 mg, 51.8% of individuals achieved ≥5% weight loss versus 24.0% with placebo (odds ratio 3.41 [95% CI 2.19; 5.31]; P &amp;lt; 0.0001). Liraglutide 3.0 mg was associated with significantly greater reductions in mean HbA1c and mean daytime glucose values and less need for insulin versus placebo, despite a treat-to-glycemic-target protocol. More hypoglycemic events were observed with placebo than liraglutide 3.0 mg. No new safety or tolerability issues were observed. CONCLUSIONS In individuals with overweight or obesity and insulin-treated type 2 diabetes, liraglutide 3.0 mg as an adjunct to IBT was superior to placebo regarding weight loss and improved glycemic control despite lower doses of basal insulin and without increases in hypoglycemic events.
Rethinking megafauna
2020-03-04

Concern for megafauna is increasing among scientists and non-scientists. Many studies have emphasized that megafauna play prominent ecological roles and provide important ecosystem services to humanity. But, what precisely are ‘megafauna’? Here, we critically assess the concept of megafauna and propose a goal-oriented framework for megafaunal research. First, we review definitions of megafauna and analyse associated terminology in the scientific literature. Second, we conduct a survey among ecologists and palaeontologists to assess the species traits used to identify and define megafauna. Our review indicates that definitions are highly dependent on the study ecosystem and research question, and primarily rely on ad hoc size-related criteria. Our survey suggests that body size is crucial, but not necessarily sufficient, for addressing the different applications of the term megafauna. Thus, after discussing the pros and cons of existing definitions, we propose an additional approach by defining two function-oriented megafaunal concepts: ‘keystone megafauna’ and ‘functional megafauna’, with its variant ‘apex megafauna’. Assessing megafauna from a functional perspective could challenge the perception that there may not be a unifying definition of megafauna that can be applied to all eco-evolutionary narratives. In addition, using functional definitions of megafauna could be especially conducive to cross-disciplinary understanding and cooperation, improvement of conservation policy and practice, and strengthening of public perception. As megafaunal research advances, we encourage scientists to unambiguously define how they use the term ‘megafauna’ and to present the logic underpinning their definition.
Effect of Microbial Biomass and Humic Acids on Abiotic and Biotic Magnetite Formation
2020-03-04

Magnetite (Fe<sub>3</sub>O<sub>4</sub>) is an environmentally ubiquitous mixed-valent iron (Fe) mineral, which can form via biotic or abiotic transformation of Fe(III) (oxyhydr)oxides such as ferrihydrite (Fh). It is currently unclear whether environmentally relevant biogenic Fh from Fe(II)-oxidizing bacteria, containing cell-derived organic matter, can transform to magnetite. We compared abiotic and biotic transformation: (1) abiogenic Fh (aFh); (2) abiogenic Fh coprecipitated with humic acids (aFh-HA); (3) biogenic Fh produced by phototrophic Fe(II)-oxidizer <i>Rhodobacter ferrooxidans</i> SW2 (bFh); and (4) biogenic Fh treated with bleach to remove biogenic organic matter (bFh-bleach). Abiotic or biotic transformation of Fh was promoted by Fe<sub>aq</sub><sup>2+</sup> or Fe(III)-reducing bacteria. Fe<sub>aq</sub><sup>2+</sup>-catalyzed abiotic reaction with aFh and bFh-bleach led to complete transformation to magnetite. In contrast, aFh-HA only partially (68%) transformed to magnetite, and bFh (17%) transformed to goethite. We hypothesize that microbial biomass stabilized bFh against reaction with Fe<sub>aq</sub><sup>2+</sup>. All four Fh substrates were transformed into magnetite during biotic reduction, suggesting that Fh remains bioavailable even when associated with microbial biomass. Additionally, there were poorly ordered magnetic components detected in the biogenic end products for aFh and aFh-HA. Nevertheless, abiotic transformation was much faster than biotic transformation, implying that initial Fe<sub>aq</sub><sup>2+</sup> concentration, passivation of Fh, and/or sequestration of Fe(II) by bacterial cells and associated biomass play major roles in the rate of magnetite formation from Fh. These results improve our understanding of factors influencing secondary mineralization of Fh in the environment.
Chitinase 10 controls chitin amounts and organization in the wing cuticle of Drosophila
2020-03-04

Abstract Wings are essential for insect fitness. A number of proteins and enzymes have been identified to be involved in wing terminal differentiation, which is characterized by the formation of the wing cuticle. Here, we addressed the question whether chitinase 10 (Cht10) may play an important role in chitin organization in the wings of the fruit fly Drosophila melanogaster . Initially, we first found that Cht10 expression coincides with the expression of the chitin synthase coding gene kkv . This suggests that the respective proteins may cooperate during wing differentiation. In tissue‐specific RNA interference experiments, we demonstrate that suppression of Cht10 causes an excess in chitin amounts in the wing cuticle. Chitin organization is severely disrupted in these wings. Based on these data, we hypothesize that Cht10 restricts chitin amounts produced by Kkv in order to ensure normal chitin organization and wing cuticle formation. In addition, we found by scanning electron microscopy that Cht10 suppression also affects the cuticle surface. In turn, cuticle inward permeability is enhanced in Cht10 ‐less wings. Moreover, flies with reduced Cht10 function are unable to fly. In conclusion, Cht10 is essential for wing terminal differentiation and function.
In situ observation of the percolation threshold in multiphase magma analogues
2020-03-04

Abstract Magmas vesiculate during ascent, producing complex interconnected pore networks, which can act as outgassing pathways and then deflate or compact to volcanic plugs. Similarly, in-conduit fragmentation events during dome-forming eruptions create open systems transiently, before welding causes pore sealing. The percolation threshold is the first-order transition between closed- and open-system degassing dynamics. Here, we use time-resolved, synchrotron-source X-ray tomography to image synthetic magmas that go through cycles of opening and closing, to constrain the percolation threshold Φ C at a range of melt crystallinity, viscosity and overpressure pertinent to shallow magma ascent. During vesiculation, we observed different percolative regimes for the same initial bulk crystallinity depending on melt viscosity and gas overpressure. At high viscosity (&gt; 10 6 Pa s) and high overpressure (~ 1–4 MPa), we found that a brittle-viscous regime dominates in which brittle rupture allows system-spanning coalescence at a low percolation threshold ( Φ C ~0.17) via the formation of fracture-like bubble chains. Percolation was followed by outgassing and bubble collapse causing densification and isolation of the bubble network, resulting in a hysteresis in the evolution of connectivity with porosity. At low melt viscosity and overpressure, we observed a viscous regime with much higher percolation threshold ( Φ C &gt; 0.37) due to spherical bubble growth and lower degree of crystal connection. Finally, our results also show that sintering of crystal-free and crystal-bearing magma analogues is characterised by low percolation thresholds ( Φ C = 0.04 – 0.10). We conclude that the presence of crystals lowers the percolation threshold during vesiculation and may promote outgassing in shallow, crystal-rich magma at initial stages of Vulcanian and Strombolian eruptions.
Divergent mammalian body size in a stable Eocene greenhouse climate
2020-03-04

Abstract A negative correlation between body size and the latitudinal temperature gradient is well established for extant terrestrial endotherms but less so in the fossil record. Here we analyze the middle Eocene site of Geiseltal (Germany), whose record is considered to span ca. 5 Myrs of gradual global cooling, and generate one of the most extensive mammalian Paleogene body size datasets outside North America. The δ 18 O and δ 13 C isotopic analysis of bioapatite reveals signatures indicative of a humid, subtropical forest with no apparent climatic change across Geiseltal. Yet, body mass of hippomorphs and tapiromorphs diverges rapidly from a respective median body size of 39 kg and 124 kg at the base of the succession to 26 kg and 223 kg at the top. We attribute the divergent body mass evolution to a disparity in lifestyle, in which both taxa maximize their body size-related selective advantages. Our results therefore support the view that intrinsic biotic processes are an important driver of body mass outside of abrupt climate events. Moreover, the taxonomy previously used to infer the duration of the Geiseltal biota is not reproducible, which precludes chronological correlation with Eocene marine temperature curves.
Therapeutic iloprost for the treatment of acute respiratory distress syndrome (ARDS) (the ThIlo trial): a prospective, randomized, multicenter phase II study
2020-03-04

Abstract Background Acute respiratory distress syndrome (ARDS) is caused by rapid-onset (within hours) acute inflammatory processes in lung tissue, and it is a life-threatening condition with high mortality. The treatment of ARDS to date is focused on the prevention of further iatrogenic damage of the lung rather than the treatment of the initial inflammatory process. Several preclinical studies have revealed a beneficial effect of iloprost on the control of pulmonary inflammation, and in a small number of patients with ARDS, iloprost treatment resulted in improved oxygenation. Therefore, we plan to conduct a large multicenter trial to evaluate the effect of iloprost on ARDS. Methods The Therapeutic Iloprost during ARDS trial (ThIlo trial) is a multicenter, randomized, single blinded, clinical phase II trial assessing the efficacy of inhaled iloprost for the prevention of the development and progression of ARDS in critically ill patients. One hundred fifty critically ill patients suffering from acute ARDS will be treated either by nebulized iloprost or NaCl 0.9% for 5 days. Blood samples will be drawn at defined time points to elucidate the serum levels of iloprost and inflammatory markers during treatment. Mechanical ventilation will be standardized. In follow-up visits at days 28 and 90 as well as 6 months after enrollment, functional status according to the Barthel Index and a health care-related questionnaire, and frailty (Vulnerable Elders Survey) will be evaluated. The primary endpoint is the improvement of oxygenation, defined as the ratio of PaO 2 /FiO 2 . Secondary endpoints include 90-day all-cause mortality, Sequential Organ Failure Assessment scores during the study period up to day 90, the duration of mechanical ventilation, the length of intensive care unit (ICU) stay, ventilator-associated pneumonia, delirium, ICU-acquired weakness, and discharge localization. The study will be conducted in three university ARDS centers in Germany. Discussion The results of the ThIlo trial will highlight the anti-inflammatory effect of iloprost on early inflammatory processes during ARDS, resulting in the improvement of outcome parameters in patients with ARDS. Trial registration EUDRA-CT: 2016-003168-37. Registered on 12 April 2017. ClinicalTrials.gov : NCT03111212 . Registered on 4 June 2017.
Support of students in primary schools: a comparative case study in a selective education system
2020-03-04

Previous research has demonstrated that school processes can be significantly associated with (in)equality in schools. However, it is unclear what these practices in schools look like. This study aims to understand support practices for students in primary schools in a highly selective education system. The findings are based on a contrastive case comparison of five primary schools in Switzerland with a large percentage of children with a migration background. Quantitative surveys with students in Grades 4, 5, and 6 (n = 372) and qualitative analyses of group discussions with teachers were conducted. The results of the qualitative study, and in part also of the quantitative study, show that schools differ systematically in providing support for students. None of the schools was found to have a support milieu that could be described as non-discriminatory. In the majority of the schools, the support milieu is oriented towards high performing students with a higher socio-cultural family background or high educational aspirations; this may lead to the reproduction of inequalities. Only two schools seem to have implemented compensatory support strategies, at least partially. Further, the schools can be differentiated regarding the teachers’ perceived degree of their active participation in supporting students.
Carotid Intima-Media Thickness is a Predictor of Subclinical Myocardial Damage in Men with Type 2 Diabetes Mellitus
2020-03-04

Abstract Background Type 2 diabetes mellitus (T2DM) promotes the development of atherosclerosis and is a major risk factor for cardiovascular disease. High-sensitivity cardiac troponin I (hs-cTnI) assays fundamentally improved the diagnosis of myocardial injury and even enable the prediction of future cardiovascular events in the general population. However, data about the association of hs-cTnI with cardiovascular risk factors and carotid intima media thickness (cIMT) as a marker of atherosclerosis are limited, especially in patients with T2DM. Methods In this cross-sectional study we analyzed clinical and laboratory parameters of 234 patients (43% women) with T2DM and a median age of 65 years (interquartile range: 57–71). The median duration of diabetes mellitus was 10 years (6–17). Anthropometric data, blood pressure, glycemic parameters and lipid profiles were determined. Hs-cTnI plasma concentrations were measured on an ADVIA Centaur XPT immunoassay analyzer and cIMT was evaluated by high-resolution ultrasound. Results Hs-cTnI plasma concentrations were below the gender-specific 99th percentile in 93% of T2DM patients with a median concentration of 4.0 ng/l (interquartile range: 2.0–10.0). Hs-cTnI was significantly associated with gender, renal function and C-reactive protein in the entire study cohort. Gender-specific analyses revealed cIMT and renal function to be significantly associated with hs-cTnI in men. Contrary, only age was significantly associated with hs-cTnI in women. Conclusion In a real-world clinical setting in patients with T2DM, cIMT is a predictor of subclinical myocardial damage in men, but not in women.
Data for "A systematic evaluation of interneuron morphology representations for cell type discrimination"
2020-03-04

This folder contains all the data to reproduce the figures of the publication <em>A systematic evaluation of interneuron morphology representations for cell type discrimination (</em>https://doi.org/10.1101/591370<em>).</em> statistic_descriptions.csv : links each feature's statistic_id with a short description classification: This folder holds the multi-class and the pairwise classification performances of all feature representations (relevant for figure 4 and figure 5). It also holds the pickled multi-class models trained on morphometric statistics which coefficients are visualized in figure S5. embedding_data: This folder holds all the data used for the t-SNE visualizations of figure 8 and S4. features: This folder holds all computed feature representations of each data set and each modality (full, axon, dendrite). Features are indexed by a statistic id. Some example features are shown in figure 2. Careful, this folder is large (~6GB)! reconstructions: This folder contains all the neural reconstructions used for figure 1.
Indexing brain state-dependent pupil dynamics with simultaneous fMRI and optical fiber calcium recording
2020-03-05

Pupillometry, a noninvasive measure of arousal, complements human functional MRI (fMRI) to detect periods of variable cognitive processing and identify networks that relate to particular attentional states. Even under anesthesia, pupil dynamics correlate with brain-state fluctuations, and extended dilations mark the transition to more arousable states. However, cross-scale neuronal activation patterns are seldom linked to brain state-dependent pupil dynamics. Here, we complemented resting-state fMRI in rats with cortical calcium recording (GCaMP-mediated) and pupillometry to tackle the linkage between brain-state changes and neural dynamics across different scales. This multimodal platform allowed us to identify a global brain network that covaried with pupil size, which served to generate an index indicative of the brain-state fluctuation during anesthesia. Besides, a specific correlation pattern was detected in the brainstem, at a location consistent with noradrenergic cell group 5 (A5), which appeared to be dependent on the coupling between different frequencies of cortical activity, possibly further indicating particular brain-state dynamics. The multimodal fMRI combining concurrent calcium recordings and pupillometry enables tracking brain state-dependent pupil dynamics and identifying unique cross-scale neuronal dynamic patterns under anesthesia.
Cell type composition and circuit organization of clonally related excitatory neurons in the juvenile mouse neocortex
2020-03-05

Clones of excitatory neurons derived from a common progenitor have been proposed to serve as elementary information processing modules in the neocortex. To characterize the cell types and circuit diagram of clonally related excitatory neurons, we performed multi-cell patch clamp recordings and Patch-seq on neurons derived from Nestin-positive progenitors labeled by tamoxifen induction at embryonic day 10.5. The resulting clones are derived from two radial glia on average, span cortical layers 2–6, and are composed of a random sampling of transcriptomic cell types. We find an interaction between shared lineage and connection type: related neurons are more likely to be connected vertically across cortical layers, but not laterally within the same layer. These findings challenge the view that related neurons show uniformly increased connectivity and suggest that integration of vertical intra-clonal input with lateral inter-clonal input may represent a developmentally programmed connectivity motif supporting the emergence of functional circuits.
Patterns of physical activity-related health competence: stability over time and associations with subjective health indicators
2020-03-05

Abstract Objective If individuals want to integrate health-enhancing physical activity in their everyday life, they need specific competences. This person-oriented study aimed to: 1) Identify patterns of physical activity-related health competence, 2) examine how structurally and individually stable these patterns are over 4 months and 3) test how changes in patterns are associated with changes in subjective health indicators. Materials and methods A total of 769 individuals (82% women, M age = 27 years) were recruited from exercise courses offered by university sport. Four facets of physical activity-related health competence (control competence for physical training, physical activity-specific affect regulation, self-determined motivation for exercise, physical activity-specific self-control) and subjective health (subjective vitality and perceived fitness) were measured twice. Patterns were identified using latent profile analysis. Their stability and associations with subjective health changes were examined with latent transition analyses and a configural frequency analysis. Results Seven patterns of physical activity-related health competence were identified. Besides three level patterns, four shape patterns were found with differing ratings across the studied variables (e.g. average values for control competence for physical training, self-determined motivation and physical activity-specific self-control, but a high level in physical activity affect regulation). These patterns proved to be structurally stable over time. In all, 72% of the individuals stayed in the same pattern, whereas 20% moved to a more and 8% to a less competent pattern. Changes in patterns are linked to change in subjective vitality and perceived fitness. Conclusion The results presented here demonstrate the added value of using a person-oriented approach to investigate development of physical activity-related health competence. Furthermore, they generate knowledge for designing tailored interventions.