julilili42/papers huggingface dataset:
Bipolar-associated miR-499-5p controls neuroplasticity by downregulating the Cav1.2 L-type voltage gated calcium channel subunit CACNB2
2021-06-10

ABSTRACT Bipolar disorder (BD) is a chronic mood disorder characterized by alternating manic and depressive episodes, often in conjunction with cognitive deficits. Dysregulation of neuroplasticity and calcium homeostasis as a result of complex genetic environment interactions are frequently observed in BD patients, but the underlying molecular mechanisms are largely unknown. Here, we show that a BD-associated microRNA, miR-499-5p, regulates neuronal dendrite development and cognitive function by downregulating the BD risk gene CACNB2 . miR-499-5p expression is increased in peripheral blood of BD patients and healthy subjects at risk of developing the disorder due to a history of childhood maltreatment. This up-regulation is paralleled in the hippocampus of rats which underwent juvenile social isolation. Elevating miR-499-5p levels in rat hippocampal pyramidal neurons impairs dendritogenesis and reduces surface expression and activity of the voltage-gated L-type calcium channel Ca v 1.2. We further identified CACNB2 , which encodes a regulatory β-subunit of Ca v 1.2, as a direct target of miR-499-5p in neurons. CACNB2 downregulation is required for the miR-499-5p dependent impairment of dendritogenesis, suggesting that CACNB2 is an important downstream target of miR-499-5p in the regulation of neuroplasticity. Finally, elevating miR-499-5p in the hippocampus in vivo is sufficient to induce short-term memory impairments in rats haploinsufficient for the Ca v 1.2 pore forming subunit Cacna1c . Taken together, we propose that stress-induced upregulation of miR-499-5p contributes to dendritic impairments and deregulated calcium homeostasis in BD, with specific implications for the neurocognitive dysfunction frequently observed in BD patients.
Removal of micropollutants and biological effects by conventional and intensified constructed wetlands treating municipal wastewater
2021-06-11

Seven treatment wetlands and a municipal wastewater treatment plant (WWTP) were weekly monitored over the course of one year for removal of conventional wastewater parameters, selected micropollutants (caffeine, ibuprofen, naproxen, benzotriazole, diclofenac, acesulfame, and carbamazepine) and biological effects. The treatment wetland designs investigated include a horizontal subsurface flow (HF) wetland and a variety of wetlands with intensification (aeration, two-stages, or reciprocating flow). Complementary to the common approach of analyzing individual chemicals, in vitro bioassays can detect the toxicity of a mixture of known and unknown components given in a water sample. A panel of five in vitro cell-based reporter gene bioassays was selected to cover environmentally relevant endpoints (AhR: indicative of activation of the aryl hydrocarbon receptor; PPARγ: binding to the peroxisome proliferator-activated receptor gamma; ERα: activation of the estrogen receptor alpha; GR: activation of the glucocorticoid receptor; oxidative stress response). While carbamazepine was persistent in the intensified treatment wetlands, mean monthly mass removal of up to 51% was achieved in the HF wetland. The two-stage wetland system showed highest removal efficacy for all biological effects (91% to >99%). The removal efficacy for biological effects ranged from 56% to 77% for the HF wetland and 60% to 99% for the WWTP. Bioanalytical equivalent concentrations (BEQs) for AhR, PPARγ, and oxidative stress response were often below the recommended effect-based trigger (EBT) values for surface water, indicating the great benefit for using nature-based solutions for water treatment. Intensified treatment wetlands remove both individual micropollutants and mixture effects more efficiently than conventional (non-aerated) HF wetlands, and in some cases, the WWTP.
Nitrate Removal by a Novel Lithoautotrophic Nitrate-Reducing, Iron(II)-Oxidizing Culture Enriched from a Pyrite-Rich Limestone Aquifer
2021-06-11

Removal of nitrate by microbial denitrification in groundwater is often limited by low concentrations of organic carbon. In these carbon-poor ecosystems, nitrate-reducing bacteria that can use inorganic compounds such as Fe(II) (NRFeOx) as electron donors could play a major role in nitrate removal.
Exploring the Many-Body Dynamics Near a Conical Intersection with Trapped Rydberg Ions
2021-06-11

Conical intersections between electronic potential energy surfaces are paradigmatic for the study of nonadiabatic processes in the excited states of large molecules. However, since the corresponding dynamics occurs on a femtosecond timescale, their investigation remains challenging and requires ultrafast spectroscopy techniques. We demonstrate that trapped Rydberg ions are a platform to engineer conical intersections and to simulate their ensuing dynamics on larger length scales and timescales of the order of nanometers and microseconds, respectively; all this in a highly controllable system. Here, the shape of the potential energy surfaces and the position of the conical intersection can be tuned thanks to the interplay between the high polarizability and the strong dipolar exchange interactions of Rydberg ions. We study how the presence of a conical intersection affects both the nuclear and electronic dynamics demonstrating, in particular, how it results in the inhibition of the nuclear motion. These effects can be monitored in real time via a direct spectroscopic measurement of the electronic populations in a state-of-the-art experimental setup.
The Judgment of the German Federal Constitutional Court regarding assisted suicide: a template for pluralistic states?
2021-06-11

The article presents the judgment of the German Federal Constitutional Court from 26 February 2020 on assisted suicide. The statements regarding human dignity, human rights and the relationship between citizens and the state are examined. Furthermore, the consequences resulting from this interpretation of human dignity for states that are pluralistic and based on human rights will be laid out. The court’s judgment limits the power of parliaments and poses a challenge to many laws in states that see themselves as pluralistic, human rights-based states.
Oscillation dynamics of scalarized neutron stars
2021-06-11

Scalar-tensor theories are well studied extensions of general relativity that offer deviations which are yet within observational boundaries. We present the time evolution equations governing the perturbations of a nonrotating scalarized neutron star, including a dynamic spacetime as well as scalar field within the framework of such scalar-tensor theories. We employ a theory that allows for a massive scalar field or a self-interaction term and we study the impact of those parameters on the non-axisymmetric -mode. The time evolution approach allows for a comparatively simple implementation of the boundary conditions. We find that the -mode frequency is no longer a simple function of the star's average density when a scalar field is present. We also evaluate the accuracy of different variants of the Cowling approximation commonly used in previous studies of neutron star oscillation modes in alternative theories of gravity and demonstrate that it can give us not only qualitatively correct results, but in some cases also good quantitative estimates of the oscillations frequencies.
Shape-invariant encoding of dynamic primate facial expressions in human perception
2021-06-11

Dynamic facial expressions are crucial for communication in primates. Due to the difficulty to control shape and dynamics of facial expressions across species, it is unknown how species-specific facial expressions are perceptually encoded and interact with the representation of facial shape. While popular neural network models predict a joint encoding of facial shape and dynamics, the neuromuscular control of faces evolved more slowly than facial shape, suggesting a separate encoding. To investigate these alternative hypotheses, we developed photo-realistic human and monkey heads that were animated with motion capture data from monkeys and humans. Exact control of expression dynamics was accomplished by a Bayesian machine-learning technique. Consistent with our hypothesis, we found that human observers learned cross-species expressions very quickly, where face dynamics was represented largely independently of facial shape. This result supports the co-evolution of the visual processing and motor control of facial expressions, while it challenges appearance-based neural network theories of dynamic expression recognition.
Patients with Primary Central Nervous System Lymphoma Not Eligible for Clinical Trials: Prognostic Factors, Treatment and Outcome
2021-06-11

Patients with primary central nervous system lymphoma (PCNSL) not fulfilling inclusion criteria for clinical trials represent an underreported population. Thirty-four consecutive PCNSL patients seen at our center between 2005 and 2019 with exclusion criteria for therapeutic trials were analyzed (non-study patients) and compared with patients from the G-PCNSL-SG-1 (German PCNSL Study Group 1) study (study patients), the largest prospective multicenter trial on PCNSL, comprising 551 patients. Median follow up was 68 months (range 1–141) in non-study patients and 51 months (1–105) in study patients. Twenty-seven/34 (79.4%) non-study patients received high dose methotrexate (HDMTX), while seven/34 (20.6%) with a glomerular filtration rate (GFR) &lt; 50 mL/min did not. Median overall survival (OS) was six months (95% confidence interval [CI] 0–21 months) in those 34 non-study patients. The 27 non-study patients treated with HDMTX were compared with 526/551 G-PCNSL-SG-1 study patients who had received HDMTX as well. Median OS was 20 months (95% CI 0–45)/21 months (95% CI 18–25) in 27 non-study/526 study patients (p = 0.766). Favorable prognostic factors in non-study patients were young age, application of HDMTX and early response on magnet resonance imaging (MRI). If HDMTX-based chemotherapy can be applied, long-term disease control is possible even in patients not qualifying for clinical trials. Initial response on early MRI might be useful for decision on treatment continuation.
Consciousness is supported by near-critical cortical electrodynamics
2021-06-11

Mounting evidence suggests that during conscious states, the electrodynamics of the cortex are poised near a critical point or phase transition, and that this near-critical behavior supports the vast flow of information through cortical networks during conscious states. Here, for the first time, we empirically identify the specific critical point near which conscious cortical dynamics operate as the edge-of-chaos critical point, or the boundary between periodicity/stability and chaos/instability. We do so by applying the recently developed modified 0-1 chaos test to electrocorticography (ECoG) and magne-toencephalography (MEG) recordings from the cortices of humans and macaques across normal waking, generalized seizure, GABAergic anesthesia, and psychedelic states. Our evidence suggests that cortical information processing is disrupted during unconscious states because of a transition of cortical dynamics away from this critical point; conversely, we show that psychedelics may increase the information-richness of cortical activity by tuning cortical electrodynamics closer to this critical point. Finally, we analyze clinical electroencephalography (EEG) recordings from patients with disorders of consciousness (DOC), and show that assessing the proximity of cortical electrodynamics to the edge-of-chaos critical point may be clinically useful as a new biomarker of consciousness. Significance Statement What changes in the brain when we lose consciousness? One possibility is that the loss of consciousness corresponds to a transition of the brain’s electric activity away from edge-of-chaos criticality, or the knife’s edge in between stability and chaos. Recent mathematical developments have produced novel tools for testing this hypothesis, which we apply for the first time to cortical recordings from diverse brain states. We show that the electric activity of the cortex is indeed poised near the boundary between stability and chaos during conscious states and transitions away from this boundary during unconsciousness, and that this transition disrupts cortical information processing.
Generation and characterization of the human induced pluripotent stem cell line NMIi010-A from peripheral blood mononuclear cells of a healthy 49–year old male individual
2021-06-11

Peripheral-blood derived CD34<sup>+</sup> hematopoietic stem and progenitor cells were isolated from a 49-year old male donor and were successfully reprogrammed into human induced pluripotent stem cells (hiPSCs) using integration-free episomal vectors. The hiPSC line exhibited a typical stem cell-like morphology and endogenously expressed several pluripotency markers by concomitant loss of exogenous reprogramming vectors. Genomic integrity was confirmed by microarray-based comparative genomic hybridization (array CGH). Further analysis affirmed the ability of this hiPSC line to differentiate into all three germ layers. Thus, the reported cell line may serve as a healthy control for disease modeling.
Liquid–liquid phase separation in an inhomogeneous ternary colloid–polymer mixture
2021-06-11

Suspended colloids are often considered as models for molecules, which are sufficiently big so that they can be observed directly in (light) microscopes and for which the effective interaction among each other can be tailored. The Asakura–Oosawa model of ideal colloid–polymer mixtures captures the idea of tuning the interaction between the colloids via a potential, which possesses a range set by the size of the polymers and an attractive strength characterized by the (reservoir) number density of the polymers, which plays the role of an inverse temperature. The celebrated Asakura–Oosawa depletion potential allows one to recreate the bulk phase diagram of a simple fluid by employing a colloid–polymer mixture. This has been verified in theory, by computer simulations, and via experiments. Here, we study the phase behavior of a confined colloid–polymer mixture with two polymer species. The sizes and densities are chosen such that the resulting bulk phase diagram exhibits a second stable critical point within the framework of the classical density functional theory. Our results suggest that a suitably tuned colloid–polymer mixture can be an interesting model system to study fluids with two critical points.
Thyroid Metastasis in Whole-Body 18F-FDG PET/CT Restaging of Small Cell Lung Cancer
2021-06-11

Abstract Incidental findings of thyroid lesions, some of which show increased FDG uptake, are common in whole-body FDG PET/CT imaging of oncological patients. As metastases to the thyroid are extremely rare, it is often a matter of debate, whether thyroid lesions should be considered as benign goiter or evaluated further. Here, we present the case of a 65-year-old woman with history of small cell lung cancer and multiple thyroid lesions, classified as benign nodular goiter. Because in restating using 18 F-FDG PET/CT these lesions showed an increased FDG uptake and growth progression, decision was made for fine-needle aspiration, which revealed small cell lung cancer metastasis 14 months after first tumor diagnosis.
Spatial neglect in the digital age – Influence of presentation format on patients’ test behavior
2021-06-11

Abstract Computerization of diagnostic neglect tests can deepen our knowledge of neglect specific abnormalities, by effortlessly providing additional behavioral markers that are hardly extractable from existing paper-and-pencil versions. However, so far it is not known whether the digitization and/or a change in size format impact neglect patients’ search behavior and test scores and thus require adjustments of cut-off criteria. We compared the Center of cancellation (CoC) measure of right hemisphere stroke patients with spatial neglect in two cancellation tasks across different modalities (paper-and-pencil vs. digital) and display sizes (small, medium, large). We found that the CoC measure did neither vary considerably between paper-and-pencil versus digital versions, nor between different digital size formats. The CoC derived from cancellation tasks thus seems robust to test digitization. A further aim of the present study was to evaluate three additional parameters of search behavior which became available through digitization. We observed slower search behavior, increased distance between two consecutively identified items, and signs of a more strategic search for neglect patients than control patients without neglect. Machine learning classifications indicated that – beyond the CoC measure – the latter three variables can help to differentiate stroke patients with spatial neglect from thosewithout.
Self-assembled nanoparticles enable delivery of VCP inhibitor, resulting in enhanced photoreceptor protection in retinal explants
2021-06-11

1. Abstract Mutations in rhodopsin lead to its misfolding resulting in autosomal dominant retinitis pigmentosa (adRP). Pharmacological inhibition of the ATP-driven chaperone valosin- containing protein (VCP), a molecular checkpoint for protein quality control, slows down retinal degeneration in animal models. However, poor water-solubility of VCP inhibitors poses a challenge to their clinical translation as intravitreal injections for retinal treatment. In order to enable the delivery of VCP inhibitors, we have developed and investigated two formulations for the VCP inhibitor ML240. Nanoformulations of ML240 were obtained by using amphiphilic polymers methoxy-poly (ethylene glycol) 5kDa -cholane (mPEG 5kDa -cholane) and methoxy-poly (ethylene glycol) 5kDa - cholesterol (mPEG 5kDa -cholesterol). Both formulations increased the water-solubility of ML240 by two orders of magnitude and prolonged the drug released over ten days. Encapsulation of ML240 in mPEG 5kDa -cholane showed superior photoreceptor protection at lower drug concentrations, normalized rhodopsin localization, and alleviated inflammatory microglial responses in an ex vivo rat model of retinal degeneration. The study demonstrates the potential of VCP inhibitor nanoformulations to treat adRP, a pharmacologically orphan disease.
Contours of a ‘Post-Critical’ Cartography—A Contribution to the Dissemination of Sociological Cartographic Research
2021-06-12

Abstract Since the 1980s, ‘critical cartography’ has been developing. Its merits lie in its awareness of the socially constructed nature of cartographic representations, the power relations involved, and the process-bound nature of cartographic practices. The ‘post-critical’ cartography proposed here takes up these merits but does so without following the categorical rejection of positivist ‘traditional’ cartography or the moral demarcation of what can and cannot be represented as well as the subordination of theories to the ‘critical’ paradigm. Instead, the ‘post-critical’ approach relies on the struggle for suitable theoretical frameworks—the normative reference horizon within the endeavor of cartography is the enhancement of life chances. In this respect, the prefix ‘post’ refers not only to a temporal ‘after’, but also to the perpetuation of central concerns of ‘critical’ cartography, simultaneously freeing it from such limitations.
A history of previous childbirths is linked to women's white matter brain age in midlife and older age
2021-06-12

Abstract Maternal brain adaptations occur in response to pregnancy, but little is known about how parity impacts white matter and white matter ageing trajectories later in life. Utilising global and regional brain age prediction based on multi‐shell diffusion‐weighted imaging data, we investigated the association between previous childbirths and white matter brain age in 8,895 women in the UK Biobank cohort (age range = 54–81 years). The results showed that number of previous childbirths was negatively associated with white matter brain age, potentially indicating a protective effect of parity on white matter later in life. Both global white matter and grey matter brain age estimates showed unique contributions to the association with previous childbirths, suggesting partly independent processes. Corpus callosum contributed uniquely to the global white matter association with previous childbirths, and showed a stronger relationship relative to several other tracts. While our findings demonstrate a link between reproductive history and brain white matter characteristics later in life, longitudinal studies are required to establish causality and determine how parity may influence women's white matter trajectories across the lifespan.
Short-term variability of proton density fat fraction in pancreas and liver assessed by multi-echo chemical-shift encoding-based MRI at 3 T
2021-06-12

Abstract BACKGROUND Quantification of pancreatic fat (PF) and intrahepatic lipids (IHL) is of increasing interest in cross-sectional epidemiological and interventional studies in subjects at risk for metabolic diseases. Up to now, short- and medium-term variations as well as their dependence on actual nutritional status are almost unknown. PURPOSE or HYPOTHESIS To assess short-term intraday variations of PF/IHL after a high-fat meal as well as medium-term changes after 5 days of high-caloric diet with a 1500 kcal surplus on individual daily energy requirement. STUDY TYPE (retrospective/prospective/longitudinal/case control/cohort etc.) Prospective cohort study. SUBJECTS Twelve healthy subjects (6m/6f) for intraday variations, 15 healthy male subjects for medium-term high-caloric diet and 11 age- and BMI-matched controls. FIELDSTRENGTH/SEQUENCE 3 T whole-body imager (Magnetom Vida, Siemens Healthineers, Erlangen, Germany), assessment of proton density fat fraction by chemical-shift encoded MRI (multi-echo gradient echo sequence, qDixon). ASSESSMENT Manually drawn regions of interest in head, body and tail of pancreas as well as in liver by an experienced medical physicist carefully avoiding inclusion of surrounding visceral fat (pancreas) or blood-vessels (liver). STATISTICAL TESTS (please list the significance level) Repeated measurements Anova for variabilities of PF and IHL, linear correlation analyses for relation of PF, IHL and BMI. Significance level p &lt; 0.05 for all. RESULTS (must have numerical data and statistical testing for each phrase) Non-significant changes in PF in both studies (2.5±0.9 vs. 2.5±1.0% after high-fat meal, 1.4±0.8 vs. 1.6±0.6% after high-caloric diet and 1.6±0.7 vs. 1.8±1.0% in the isocaloric control group), unchanged IHL after high-fat meal (2.5±0.9 vs. 2.4±1.0 %) and in the control group (1.1±0.6 vs. 1.2±1.1%), but significantly increased IHL after 5-day high-caloric diet (1.6±2.2% vs. 2.6±3.6%, p &lt; 0.05). DATA CONCLUSION Daytime and nutritional status have no significant influence on ectopic fat depots in pancreas and liver and will therefore represent no major confounders in epidemiologic or clinical studies.