julilili42/papers huggingface dataset:
Neurovascular Uncoupling: Multimodal Imaging Delineates the Acute Effects of MDMA
2022-02-16

Abstract Psychedelic compounds have attracted increasing interest in recent years due to their therapeutic potential for psychiatric disorders. Methylenedioxymethamphetamine (MDMA) is currently being investigated in clinical trials to treat post-traumatic stress disorder. To understand the acute effects of psychedelic drugs in vivo , functional MR imaging (fMRI) has been widely used in recent years. Notably, fMRI studies have shown that MDMA leads to inhibition of brain activity, challenging earlier hypotheses indicating mainly excitatory effects. However, interpretation of hemodynamic changes induced by psychedelics is challenging because of the potent vascular effects associated with this class of substances. Therefore, this study aimed to investigate the acute effects of MDMA using simultaneous positron emission tomography (PET)/fMRI in rats. For this purpose, hemodynamic changes measured by BOLD-fMRI were related to alterations in glucose utilization and serotonin transporter (SERT) occupancy, investigated using [ 18 F]FDG functional PET (fPET) and [ 11 C]DASB PET. We demonstrate that MDMA induces global hemodynamic decreases accompanied by localized metabolic increases. Elevated metabolism was found primarily in limbic projection areas involved in emotion processing. Concurrent BOLD-fMRI decreases, also found in extracerebral areas, indicate that the BOLD-fMRI reductions observed in the brain are of vascular, non-neuronal origin. We further show that higher SERT occupancy strongly correlates with regional BOLD-fMRI reductions. Therefore, increased serotonin levels induced by SERT blockage may cause a neurovascular uncoupling. Correct understanding of the in vivo mechanism of MDMA not only supports ongoing research but also warrants a reassessment of previous studies on neuronal effects of psychedelics relying on neurovascular coupling.
Stereo viewing upsets cinematic continuity: Filmic cuts are more salient in 3D than in 2D movies
2022-02-16

Filmmakers have established editing rules that aim to create cinematic continuity across filmic cuts, thereby avoiding viewers’ confusion despite the abrupt changes in perception. In our present project, we investigated the impact of 3D films, as opposed to 2D films, on the salience of filmic cuts. We employed a cut detection task and focused on within-scene cuts with mere changes in camera perspective. We presented short video clips to our participants and asked them to press a key whenever they noticed a filmic cut, and we measured their cut detection performance. In addition to viewing mode (2D vs. 3D presentation), we considered cross-modal auditory influences (visual vs. audiovisual presentation) on the salience of filmic cuts. Participants detected cuts more accurately and faster when the video clips were presented in 3D rather than in 2D and when the video clips were presented only visually (without soundtrack) rather than audiovisually (with soundtrack). Both factors influenced cut detection performance independently. We conclude that while the regular audiovisual presentation of films supports the filmmakers’ mission to achieve cinematic continuity, filmmakers should also be aware of the additional salience of cuts that comes with 3D film presentation and consider its effects on cinematic continuity.
Network structure and transcriptomic vulnerability shape atrophy in frontotemporal dementia
2022-02-17

Abstract Connections among brain regions allow pathological perturbations to spread from a single source region to multiple regions. Patterns of neurodegeneration in multiple diseases, including behavioural variant of frontotemporal dementia (bvFTD), resemble the large-scale functional systems, but how bvFTD-related atrophy patterns relate to structural network organization remains unknown. Here we investigate whether neurodegeneration patterns in sporadic and genetic bvFTD are conditioned by connectome architecture. Regional atrophy patterns were estimated in both genetic bvFTD (75 patients, 247 controls) and sporadic bvFTD (70 patients, 123 controls). First, we identified distributed atrophy patterns in bvFTD, mainly targeting areas associated with the limbic intrinsic network and insular cytoarchitectonic class. Regional atrophy was significantly correlated with atrophy of structurally- and functionally-connected neighbours, demonstrating that network structure shapes atrophy patterns. The anterior insula was identified as the predominant group epicentre of brain atrophy using data-driven and simulation-based methods, with some secondary regions in frontal ventromedial and antero-medial temporal areas. We found that FTD-related genes, namely C9orf72 and TARDBP, confer local transcriptomic vulnerability to the disease, modulating the propagation of pathology through the connectome. Collectively, our results demonstrate that atrophy patterns in sporadic and genetic bvFTD are jointly shaped by global connectome architecture and local transcriptomic vulnerability, providing an explanation as to how heterogenous pathological entities can lead to the same clinical syndrome.
The RD‐Connect Genome‐Phenome Analysis Platform: Accelerating diagnosis, research, and gene discovery for rare diseases
2022-02-17

Rare disease patients are more likely to receive a rapid molecular diagnosis nowadays thanks to the wide adoption of next-generation sequencing. However, many cases remain undiagnosed even after exome or genome analysis, because the methods used missed the molecular cause in a known gene, or a novel causative gene could not be identified and/or confirmed. To address these challenges, the RD-Connect Genome-Phenome Analysis Platform (GPAP) facilitates the collation, discovery, sharing, and analysis of standardized genome-phenome data within a collaborative environment. Authorized clinicians and researchers submit pseudonymised phenotypic profiles encoded using the Human Phenotype Ontology, and raw genomic data which is processed through a standardized pipeline. After an optional embargo period, the data are shared with other platform users, with the objective that similar cases in the system and queries from peers may help diagnose the case. Additionally, the platform enables bidirectional discovery of similar cases in other databases from the Matchmaker Exchange network. To facilitate genome-phenome analysis and interpretation by clinical researchers, the RD-Connect GPAP provides a powerful user-friendly interface and leverages tens of information sources. As a result, the resource has already helped diagnose hundreds of rare disease patients and discover new disease causing genes.
Equatorial extreme-mass-ratio inspirals in Kerr black holes with scalar hair spacetimes
2022-02-17

In this work we analyze some judiciously chosen solutions of Kerr Black Holes\\nwith Scalar Hair (KBHsSH) of special interest for Gravitational Wave (GW)\\nevents originated from Extreme Mass Ratio Inspirals (EMRIs). Because of the\\noff-center distribution of energy density, these spacetimes are warped in such\\na way that not all metric functions behave monotonically on the equatorial\\nplane as in the exterior region of Kerr black holes (KBHs). This has great\\nimpact on the orbital parameters, which in turn affects the imprints on signals\\ndescendant from EMRIs in a adiabatic evolution. By investigating circular obit\\nparameters, we unveil what qualitative features could be present in the signals\\nthat are new and distinct compared to KBHs, and we evolve some inspirals by\\nemploying the usual quadrupole formula approximation. We show that the\\nfrequencies of the emitted signals behave nonmonotonically, i.e. they can\\nbackward chirp, and for some particular cases they can become arbitrarily\\nsmall, falling below LISA's sensibility range. Finally, we present two sets of\\nwaveforms produced by a noncircular EMRI in which the compact object (CO)\\nfollows a type of geodesic motion typically present in spacetimes with a static\\nring (SR), in which the compact object is periodically momentarily at rest.\\n
A network of cytosolic (co)chaperones promotes the biogenesis of mitochondrial signal-anchored outer membrane proteins
2022-02-17

Abstract Signal-anchored (SA) proteins are anchored into the mitochondrial outer membrane (OM) via a single transmembrane segment at their N-terminus while the bulk of the proteins is facing the cytosol. These proteins are encoded by nuclear DNA, translated on cytosolic ribosomes, and are then targeted to the organelle and inserted into its OM by import factors. Recently, research on the insertion mechanisms of these proteins into the mitochondrial OM have gained a lot of attention. In contrast, the early cytosolic steps of their biogenesis are unresolved. Using various proteins from this category and a broad set of in vivo, in organello, and in vitro assays, we reconstituted the early steps of their biogenesis. We identified a subset of molecular (co)chaperones that interact with newly synthesized SA proteins, namely, Hsp70 and Hsp90 chaperones and co-chaperones from the Hsp40 family like Ydj1 and Sis1. These interactions were mediated by the hydrophobic transmembrane segments of the SA proteins. We further demonstrate that interfering with these interactions inhibits the biogenesis of SA proteins to varying extents. Finally, we could demonstrate direct interaction of peptides corresponding to the transmembrane segments of SA proteins with the (co)chaperones and reconstitute in vitro the transfer of such peptides from the Hsp70 chaperone to the mitochondrial Tom70 receptor. Collectively, this study unravels an array of cytosolic chaperones and mitochondrial import factors that facilitates the targeting and membrane integration of mitochondrial SA proteins.
International Society of Paediatric Surgical Oncology (IPSO) Surgical Practice Guidelines
2022-02-18

Most children with tumors will require one or more surgical interventions as part of the care and treatment, including making a diagnosis, obtaining adequate venous access, performing a surgical resection for solid tumors (with staging and reconstruction), performing procedures for cancer prevention and its late effects, and managing complications of treatment; all with the goal of improving survival and quality of life. It is important for surgeons to adhere to sound pediatric surgical oncology principles, as they are closely associated with improved local control and survival. Unfortunately, there is a significant disparity in survival rates in low and middle income countries, when compared to those from high income countries. The International Society of Paediatric Surgical Oncology (IPSO) is the leading organization that deals with pediatric surgical oncology worldwide. This organization allows experts in the field from around the globe to gather and address the surgical needs of children with cancer. IPSO has been invited to contribute surgical guidance as part of the World Health Organization Initiative for Childhood Cancer. One of our goals is to provide surgical guidance for different scenarios, including those experienced in High- (HICs) and Low- and Middle-Income Countries (LMICs). With this in mind, the following guidelines have been developed by authors from both HICs and LMICs. These have been further validated by experts with the aim of providing evidence-based information for surgeons who care for children with cancer. We hope that this initiative will benefit children worldwide in the best way possible. Simone Abib, IPSO President Justin T Gerstle, IPSO Education Committee Chair Chan Hon Chui, IPSO Secretary.
Binary orbital evolution driven by a circumbinary disc
2022-02-18

The question whether the interaction of a circumbinary disc with the central binary system leads to a shrinking or to an expansion of the binary orbit has attracted considerable interest as it impacts the evolution of binary black holes and stellar binary stars in their formation phase. We performed two-dimensional hydrodynamical simulations of circumbinary discs for a large parameter set of disc viscosities and thicknesses and for two different binary mass ratios for binaries on circular orbits. We measured the net angular momentum and mass transfer between disc and binary system, and evaluated the normalised specific angular momentum accretion, j s . This was compared to the theoretical, critical specific angular momentum change j s,crit that separates contracting from expanding cases, which depends on the binary mass ratio and on the relative accretion onto the two stars. Using finite and infinite disc models, we show that the inferred binary evolution is very similar for both setups, and we confirm that j s can be measured accurately with cylindrical simulations that do not include the central binary. However, to obtain the relative accretion onto the stars for non-equal mass binaries, simulations that cover the whole domain including the binary are required. We find that for thick discs with aspect ratio h = 0.1, the binaries expand for all viscosities, while discs with h = 0.05 lead to an expansion only for higher viscosities with α exceeding ∼0.005. Overall, the regime of binary expansion extends to a much wider parameter space than previously anticipated, but for thin, low-viscosity discs, the orbits shrink.
Recycling of the first atmospheres of embedded planets: Dependence on core mass and optical depth
2022-02-18

Context. Recent observations found close-in planets with significant atmospheres of hydrogen and helium in great abundance. These are the so-called super-Earths and mini-Neptunes. Their atmospheric composition suggests that they formed early during the gas-rich phase of the circumstellar disk and were able to avoid becoming hot Jupiters. As a possible explanation, recent studies explored the recycling hypothesis and showed that atmosphere-disk recycling is able to fully compensate for radiative cooling and thereby halt Kelvin-Helmholtz contraction to prevent runaway gas accretion. Aims. To understand the parameters that determine the efficiency of atmospheric recycling, we extend our earlier studies by exploring the effects of the core mass, the effect of circumstellar gas on sub-Keplerian orbits (headwind), and the optical depth of the surrounding gas on the recycling timescale. Additionally, we analyze their effects on the size and mass of the forming atmosphere. Methods. We used three-dimensional (3D) radiation-hydrodynamic simulations to model a local shearing box centered on the planet. Our planet is located at a separation of a p = 0.1 au from its solar-type host star, and we scanned the core mass range from 1 to 10 M Earth . In order to measure and track the recycling of the atmosphere, we employed tracer particles as well as tracer fluids after thermodynamic equilibrium was reached. Results. For the explored parameter space, all simulations eventually reach an equilibrium where heating due to hydrodynamic recycling fully compensates radiative cooling. In this equilibrium, the atmosphere-to-core mass ratio stays well below 10%, preventing the atmosphere from becoming self-gravitating and entering runaway gas accretion. Higher core masses cause the atmosphere to become turbulent, which further enhances recycling. Compared to the core mass, the effect of the headwind on the recycling timescale is negligible. The opacity has no significant effect on the recycling timescale, which demonstrates that the Kelvin-Helmholtz contraction timescale and the atmosphere-disk recycling timescale are independent of each other. Conclusions. Even for our highest core mass of 10 M Earth , atmosphere-disk recycling is efficient enough to fully compensate for radiative cooling and prevent the atmosphere from becoming self-gravitating. Hence, in-situ formation of hot Jupiters is very unlikely, and migration of gas giants is a key process required to explain their existence. Our findings imply that atmosphere-disk recycling is the most natural explanation for the prevalence of close-in super-Earths and mini-Neptunes.
Incretin Hypersecretion in Gestational Diabetes Mellitus
2022-02-18

Abstract Context Incretins are crucial stimulators of insulin secretion following food intake. Data on incretin secretion and action during pregnancy are sparse. Objective The aim of the study was to investigate the incretin response during an oral glucose tolerance test (OGTT) in pregnant women with and without gestational diabetes mellitus (GDM). Design We analyzed data from the ongoing observational PREG study (NCT 04270578). Setting The study was conducted at the University Hospital Tübingen. Participants We examined 167 women (33 with GDM) during gestational week 27 ± 2.2. Intervention Subjects underwent 5-point OGTT with a 75-g glucose load. Main outcome measures We assessed insulin secretion and levels of total glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), glicentin, and glucagon during OGTT. Linear regression was used to analyze the relation of GLP-1 and glucose with insulin secretion and the association of incretin levels on birth outcome. Results Insulin secretion was significantly lower in women with GDM (P &amp;lt; 0.001). Postload GLP-1 and GIP were ~20% higher in women with GDM (all P &amp;lt; 0.05) independent of age, body mass index, and gestational age. GLP-1 increase was associated with insulin secretion only in GDM, but not in normal glucose tolerance. Postprandial GLP-1 levels were negatively associated with birth weight. Conclusions The more pronounced GLP-1 increase in women with GDM could be part of a compensatory mechanism counteracting GLP-1 resistance. Higher GLP-1 levels might be protective against fetal overgrowth.
Empirical glacier mass-balance models for South America
2022-02-18

Abstract We investigate relationships between synoptic-scale atmospheric variability and the mass-balance of 13 Andean glaciers (located 16–55° S) using Pearson correlation coefficients (PCCs) and multiple regressions. We then train empirical glacier mass-balance models (EGMs) in a cross-validated multiple regression procedure for each glacier. We find four distinct glaciological zones with regard to their climatic controls: (1) The mass-balance of the Outer Tropics glaciers is linked to temperature and the El Niño-Southern Oscillation (PCC ⩽ 0.6), (2) glaciers of the Desert Andes are mainly controlled by zonal wind intensity (PCC ⩽ 0.9) and the Antarctic Oscillation (PCC ⩽0.6), (3) the mass-balance of the Central Andes glaciers is primarily correlated with precipitation anomalies (PCC ⩽ 0.8), and (4) the glacier of the Fuegian Andes is controlled by winter precipitation (PCC ≈ 0.7) and summer temperature (PCC ≈ −0.9). Mass-balance data in the Lakes District and Patagonian Andes zones, where most glaciers are located, are too sparse for a robust detection of synoptic-scale climatic controls. The EGMs yield R 2 values of ~ 0.45 on average and ⩽ 0.74 for the glaciers of the Desert Andes. The EGMs presented here do not consider glacier dynamics or geometry and are therefore only suitable for short-term predictions.
Cuprizone Intoxication Results in Myelin Vacuole Formation
2022-02-18

Myelin damage is a histopathological hallmark of multiple sclerosis lesions. Results of post mortem studies suggest that impaired myelin-axon interaction characterized by focal myelin detachments is an early event during lesion genesis. In this study, we investigated the ultrastructural changes of the axon-myelin interface in the cuprizone model using serial block face scanning electron microscopy and immunohistochemistry. We show that non-inflammatory injury of oligodendrocytes by cuprizone intoxication results in myelin vacuole formation and axonal swellings, paralleled by early alterations of the node of Ranvier cytoarchitecture. This remarkable resemblance of ultrastructural myelin characteristics in multiple sclerosis and the cuprizone animal model suggests that the cuprizone model is a valuable tool to study early pathologies during lesion formation.
Organizational roles and network effects on ideational influence in science-policy interface: Climate policy networks in Germany and Japan
2022-02-18

We examined how scientific information influences policy beliefs among organizations in climate change policy networks in Germany and Japan. Different combinations of information types, policy beliefs, and organizational roles were found to play instrumental roles. Ideational influence can occur when (1) the sender is a credible information source, (2) the receiver can understand the "message," and (3) the receiver depends on the sender's information. Organizational roles involved in this ideational influence are different in technical and political information exchange. The leverage of influence depends on the organizational ecology of different roles in each country.
A Novel, Apparently Silent Variant in MFSD8 Causes Neuronal Ceroid Lipofuscinosis with Marked Intrafamilial Variability
2022-02-18

Variants in MFSD8 can cause neuronal ceroid lipofuscinoses (NCLs) as well as nonsyndromic retinopathy. The mutation spectrum includes mainly missense and stop variants, but splice sites and frameshift variants have also been reported. To date, apparently synonymous substitutions have not been shown to cause MFSD8-associated diseases. We report two closely related subjects from a consanguineous Turkish family who presented classical features of NCLs but demonstrated marked intrafamilial variability in age at the onset and severity of symptoms. In fact, the difference in the onset of first neurologic symptoms was 15 years and that of ophthalmologic symptoms was 12 years. One subject presented an intellectual disability and a considerable cerebellar ataxia syndrome, while the other subject showed no intellectual disability and only a mild atactic syndrome. The diagnostic genetic testing of both subjects based on genome sequencing prioritized a novel, apparently synonymous variant in MFSD8, which was found in homozygosity in both subjects. The variant was not located within an integral part of the splice site consensus sequences. However, the bioinformatic analyses suggested that the mutant allele is more likely to cause exon skipping due to an altered ratio of exonic splice enhancer and silencer motifs. Exon skipping was confirmed in vitro by minigene assays and in vivo by RNA analysis from patient lymphocytes. The mutant transcript is predicted to result in a frameshift and, if translated, in a truncated protein. Synonymous variants are often given a low priority in genetic diagnostics because of their expected lack of functional impact. This study highlights the importance of investigating the impact of synonymous variants on splicing.
Environmental stress determines the colonization and impact of an endophytic fungus on invasive knotweed
2022-02-18

Abstract There is increasing evidence that microbes play a key role in some plant invasions. A diverse and widespread but little understood group of plant-associated microbes are the fungal root endophytes of the order Sebacinales. They are associated with exotic populations of invasive knotweed ( Reynoutria ssp.) in Europe, but their effects on the invaders are unknown. We used the recently isolated Sebacinales root endophyte S erendipita herbamans to experimentally inoculate invasive knotweed and study root colonisation and effects on knotweed growth under different environmental conditions. We verified the inoculation success and fungal colonisation through immunofluorescence microscopy and qPCR. We found that S. herbamans strongly colonized invasive knotweed in low-nutrient and shade environments, but much less under drought or benign conditions. At low nutrients, the endophyte had a positive effect on plant growth, whereas the opposite was true under shaded conditions. Our study demonstrates that the root endophyte S. herbamans has the potential to colonize invasive knotweed fine roots and impact its growth, and it could thus also play a role in natural populations. Our results also show that effects of fungal endophytes on plants can be strongly environment-dependent, and may only be visible under stressful environmental conditions.