bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell-type-specific analysis of alternative polyadenylation using single-cell transcriptomics data
Authors: Shulman Eldad David , Elkon Ran 
Published: September 2019

AbstractAlternative polyadenylation (APA) is emerging as an important layer of gene regulation because the majority of mammalian protein-coding genes contain multiple polyadenylation (pA) sites in their 3′ UTR. By alteration of 3′ UTR length, APA can considerably affect post-transcriptional gene regulation. Yet, our understanding of APA remains rudimentary. Novel single-cell RNA sequencing (scRNA-seq) techniques allow molecular characterization of different cell types to an unprecedented degree. Notably, the most popular scRNA-seq protocols specifically sequence the 3′ end of transcripts. Building on this property, we implemented a method for analysing patterns of APA regulation from such data. Analyzing multiple datasets from diverse tissues, we identified widespread modulation of APA in different cell types resulting in global 3′ UTR shortening/lengthening and enhanced cleavage at intronic pA sites. Our results provide a proof-of-concept demonstration that the huge volume of scRNA-seq data that accumulates in the public domain offers a unique resource for the exploration of APA based on a very broad collection of cell types and biological conditions.
Patients with end-stage kidney disease have markedly abnormal cortical hip parameters by dual-energy X-ray absorptiometry
Authors: Aleksova Jasna , Milat Frances , Kotowicz Mark A , Pasco Julie A , Schultz Chris , Wong Phillip , Ebeling Peter R , Elder Grahame J 
Published: September 2019

Abstract

Background
Patients with end-stage kidney disease (ESKD) have higher fracture rates and post-fracture mortality than the general population, but bone mineral density by dual-energy X-ray absorptiometry (DXA) is less predictive of fracture in this patient group. Bone biopsy and high-resolution imaging indicate that cortical thickness (CT) is reduced and cortical porosity is increased in ESKD. The aim of this study was to assess cortical parameters using DXA in patients with ESKD. It was hypothesized that these parameters would show deterioration and be associated with fracture.

Methods
Using advanced hip analysis, normal age-related ranges were determined from 752 female and 861 male femur scans and were compared with scans of 226 patients with ESKD at the time of transplantation.

Results
Compared with controls, female patients had lower mean±SD CT (mms) at the femoral neck (FN) (2.59 ± 1.42 versus 5.23 ± 1.85), calcar (3.46 ± 1.07 versus 5.09 ± 1.30) and shaft (4.42 ± 1.21 versus 7.44 ± 2.07; P &lt; 0.001 for each), and buckling ratios were higher (8.21 ± 4.6 versus 3.63 ± 1.42; P &lt; 0.001), indicating greater FN instability. All findings were similar for men. Prevalent fracture was documented in 28.8% of patients; 12.4% vertebral only, 8.4% non-vertebral only and 8% vertebral plus non-vertebral. In adjusted models, each 1 SD reduction in FN CT and increase in the buckling ratio was associated with a respective 1.73 (1.22–2.46)- and 1.82 (1.49–2.86)-fold increase in the risk of prevalent vertebral fracture.

Conclusions
In patients with ESKD, DXA-derived cortical parameters are markedly abnormal compared with age- and sex-matched controls. These parameters should be assessed for incident fracture prediction and targeting treatment.
Giant elephant trunks from giant molecular clouds
Authors: Sofue Yoshiaki 
Published: September 2019

AbstractWe report the discovery of large elephant trunk (ET)-like objects, named giant elephant trunks (GETs), of molecular gas in star-forming complexes in the Scutum and Norma arms using the $^{12}$CO(J = 1–0)-line survey data with the Nobeyama 45 m telescope. In comparison with the CO maps of ETs in M$\, 16$ as derived from the same data, we discuss physical properties of the GETs. Their lengths are $\sim\!\! 20$ to $50\:$pc, an order of magnitude larger than ETs. GETs show a cometary structure coherently aligned parallel to the galactic plane, and emerge from the bow-shaped concave surface of giant molecular clouds (GMC) facing the H$\,$ ii regions, and point down-stream of the gas flow in the spiral arms. The molecular masses of the head clumps are $\sim 10^{3}$–$10^{4}\, M_{\odot}$, about three to four times the virial masses, indicating that the clumps are gravitationally stable. Jeans masses calculated for the derived density and assumed kinetic temperature are commonly sub-solar. We suggest that the GET heads are possible birth sites of stellar clusters, similarly to ET globules, but at much greater scale. We discuss the origin of the GETs by Rayleigh–Taylor instability due to deceleration of GMCs by low-density gas stagnated in the galactic shock waves as well as by pressure of the H$\,$ ii regions.
The Development of Kraepelin’s Mature Diagnostic Concept of Catatonic Dementia Praecox: A Close Reading of Relevant Texts
Authors: Kendler Kenneth S 
Published: September 2019

Abstract
Through a close reading of texts, this essay traces the development of catatonia from its origination in Kahlbaum’s 1874 monograph to Kraepelin’s catatonic subtype of his new category of Dementia Praecox (DP) in 1899. In addition to Kraepelin’s second to sixth textbook editions, I examine the six articles referenced by Kraepelin: Kahlbaum 1874, Brosius 1877, Neisser 1887, Behr 1891, Schüle 1897, and Aschaffenburg 1897 (Behr and Aschaffenburg worked under Kraepelin). While Brosius and Neisser confirmed Kahlbaum’s descriptions, Behr, Schüle, and Aschaffenburg concluded that his catatonic syndrome was nonspecific and only more narrowly defined forms, especially those with deteriorating course, might be diagnostically valid. Catatonia is first described by Kraepelin as a subform of Verrücktheit (chronic nonaffective delusional insanity) in his second to fourth editions. In his third edition, he adds a catatonic form of Wahnsinn (acute delusional-affective insanity). His fourth and fifth editions contain, respectively, catatonic forms of his two proto-DP concepts: Psychischen Entartungsprocesse and Die Verblödungsprocesse. Kahlbaum’s catatonia required a sequential phasic course. Positive psychotic symptoms were rarely noted, and outcome was frequently good. While agreeing on the importance of key catatonic signs (stupor, muteness, posturing, verbigeration, and excitement), Kraepelin narrowed Kahlbaum’s concept, dropping the phasic course, emphasizing positive psychotic symptoms and poor outcome. In his fourth to sixth editions, as he tried to integrate his three DP subtypes, he stressed, as suggested by Aschaffenburg and Schüle, the close clinical relationship between catatonia and hebephrenia and emphasized the bizarre and passivity delusions seen in catatonia, typical of paranoid DP.
Toward a Neural Model of the Openness-Psychoticism Dimension: Functional Connectivity in the Default and Frontoparietal Control Networks
Authors: Blain Scott D , Grazioplene Rachael G , Ma Yizhou , DeYoung Colin G 
Published: September 2019

AbstractPsychosis proneness has been linked to heightened Openness to Experience and to cognitive deficits. Openness and psychotic disorders are associated with the default and frontoparietal networks, and the latter network is also robustly associated with intelligence. We tested the hypothesis that functional connectivity of the default and frontoparietal networks is a neural correlate of the openness-psychoticism dimension. Participants in the Human Connectome Project (N = 1003) completed measures of psychoticism, openness, and intelligence. Resting state functional magnetic resonance imaging was used to identify intrinsic connectivity networks. Structural equation modeling revealed relations among personality, intelligence, and network coherence. Psychoticism, openness, and especially their shared variance were related positively to default network coherence and negatively to frontoparietal coherence. These associations remained after controlling for intelligence. Intelligence was positively related to frontoparietal coherence. Research suggests that psychoticism and openness are linked in part through their association with connectivity in networks involving experiential simulation and cognitive control. We propose a model of psychosis risk that highlights roles of the default and frontoparietal networks. Findings echo research on functional connectivity in psychosis patients, suggesting shared mechanisms across the personality–psychopathology continuum.
Triclosan-Selected Host-Associated Microbiota Perform Xenobiotic Biotransformations in Larval Zebrafish
Authors: Weitekamp Chelsea A , Phelps Drake , Swank Adam , McCord James , Sobus Jon R , Catron Tara , Keely Scott , Brinkman Nichole , Zurlinden Todd , Wheaton Emily , Strynar Mark , McQueen Charlene , Wood Charles E , Tal Tamara 
Published: September 2019

AbstractMicrobiota regulate important physiologic processes during early host development. They also biotransform xenobiotics and serve as key intermediaries for chemical exposure. Antimicrobial agents in the environment may disrupt these complex interactions and alter key metabolic functions provided by host-associated microbiota. To examine the role of microbiota in xenobiotic metabolism, we exposed zebrafish larvae to the antimicrobial agent triclosan. Conventionally colonized (CC), microbe-free axenic (AX), or axenic colonized on day 1 (AC1) zebrafish were exposed to 0.16–0.30 µM triclosan or vehicle on days 1, 6, 7, 8, and 9 days post fertilization (dpf). After 6 and 10 dpf, host-associated microbial community structure and putative function were assessed by 16S rRNA gene sequencing. At 10 dpf, triclosan exposure selected for bacterial taxa, including Rheinheimera. Triclosan-selected microbes were predicted to be enriched in pathways related to mechanisms of antibiotic resistance, sulfonation, oxidative stress, and drug metabolism. Furthermore, at 10 dpf, colonized zebrafish contained 2.5–3 times more triclosan relative to AX larvae. Nontargeted chemical analysis revealed that, relative to AX larvae, both cohorts of colonized larvae showed elevations in 23 chemical features, including parent triclosan and putative triclosan sulfate. Taken together, these data suggest that triclosan exposure selects for microbes that harbor the capacity to biotransform triclosan into chemical metabolites with unknown toxicity profiles. More broadly, these data support the concept that microbiota modify the toxicokinetics of xenobiotic exposure.
Impact of spectrograms on the classification of wheezes and crackles in an educational setting. An interrater study
Authors: Aviles-Solis JC. , Storvoll I , Sophie Vanbelle , Melbye H. 
Published: September 2019

AbstractBackgroundChest auscultation is a widely used method in the diagnosis of lung diseases. However, the interpretation of lung sounds is a subjective task and disagreements arise. New technological developments like the use of visual representation of sounds through spectrograms could improve the agreement when classifying lung sounds, but this is not yet known.AimsTo test if the use of spectrograms improves the agreement when classifying wheezes and crackles.MethodsWe used 30 lung sounds recordings. The sample contained 15 normal recordings and 15 with wheezes or crackles. We produced spectrograms of the recordings. Twenty-three third to fifth-year medical students at UiT the Arctic University of Norway classified the recordings using an online questionnaire. We first showed the students examples of how wheezes and crackles looked in the spectrogram. Then, we played the recordings in a random order two times, first without the spectrogram, then with live spectrograms displayed. We asked them to classify the sounds for the presence of wheezes and crackles. We calculated kappa values for the agreement between each student and the expert classification with and without display of spectrograms and tested for significant improvement. We also calculated Fleiss kappa for the 23 observers with and without the spectrogram.ResultsWhen classifying wheezes 13/23 (1 with p<.05) students had a positive change in k, and 16/23 (2 with p<.05). All the statistically significant changes were in the direction of improved kappa values (.52 - .75). Fleiss kappa values were k=.51 and k=.56 (p=.63) for wheezes without and with spectrograms. For crackles, these values were k=.22 and k=.40 (p=<0.01) in the same order.ConclusionsThe use of spectrograms had a positive impact on the inter-rater agreement and the agreement with experts. We observed a higher improvement in the classification of crackles compared to wheezes.
Mobile Brain/Body Imaging of cognitive-motor impairment in multiple sclerosis: deriving EEG-based neuro-markers during a dual-task walking study
Authors: Sanctis Pierfilippo De , Malcolm Brenda R. , Mabie Peter C. , Francisco Ana A. , Mowrey Wenzhu B. , Joshi Sonja , Molholm Sophie , Foxe John J. 
Published: September 2019

ABSTRACTIndividuals with a diagnosis of multiple sclerosis (MS) often present with deficits in the cognitive as well as the motor domain. The ability to perform tasks that rely on both domains may therefore be particularly impaired. Yet, behavioral studies designed to measure costs associated with performing two tasks at the same time such as dual-task walking have yielded mixed results. Patients may mobilize additional brain resources to sustain good levels of performance. To test this hypothesis, we acquired event-related potentials (ERP) in thirteen individuals with MS and fifteen healthy control (HC) participants performing a Go/NoGo response inhibition task while sitting (i.e., single task) or walking on a treadmill (i.e., dual-task). In previous work, we showed that the nogo-N2 elicited by the cognitive task was reduced when healthy adults are also asked to walk, and that nogo-N2 reduction was accompanied by sustained dual-task performance. We predicted that some MS patients, similar to their healthy peers, may mobilize N2-indexed brain resources and thereby reduce costs. Somewhat to our surprise, the HC group performed the Go/NoGo task more accurately while walking, thus showing a dual-task benefit, whereas, in line with expectation, the MS group showed a trend towards dual-task costs. The expected nogo-N2 reduction during dual-task walking was found in the HC group, but was not present at the group level in the MS group, suggesting that this group did not modulate the nogo-N2 process in response to higher task load. Regression analysis for the pooled sample revealed a robust link between nogo-N2 reduction and better dual-task performance. We conclude that impaired nogo-N2 adaptation reflects a neurophysiological marker of cognitive-motor dysfunction in MS.
Generation of fluorescent cell-derived-matrix to study 3D cell migration
Authors: Godeau Amélie Luise , Delanoë-Ayari Hélène , Riveline Daniel 
Published: September 2019

AbstractCell migration is involved in key phenomena in biology, ranging from development to cancer. Fibroblasts move between organs in 3D polymeric networks. So far, motile cells were mainly tracked in vitro on Petri dishes or on coverslips, i.e. 2D flat surfaces, which made the extrapolation to 3D physiological environments difficult. We therefore prepared 3D Cell Derived Matrix (CDM) with specific characteristics with the goal of extracting the main readouts required to measure and characterise cell motion: cell specific matrix deformation through the tracking of fluorescent fibronectin within CDM, focal contacts as the cell anchor and acto-myosin cytoskeleton which applies cellular forces. We report our method for generating this assay of physiological-like gel with relevant readouts together with its potential impact in explaining cell motility in vivo.
Mesocorticolimbic circuit mechanisms underlying the effects of ketamine on dopamine: a translational imaging study
Authors: Kokkinou Michelle , Irvine Elaine E. , Bonsall David R. , Natesan Sridhar , Wells Lisa A. , Smith Mark , Glegola Justyna , Paul Eleanor J. , Tossell Kyoko , Veronese Mattia , Khadayate Sanjay , Dedic Nina , Hopkins Seth C. , Ungless Mark A. , Withers Dominic J. , Howes Oliver D. 
Published: September 2019

ABSTRACTPatients with schizophrenia show increased striatal dopamine synthesis capacity in imaging studies. However, the mechanism underlying this is unclear but may be due to N-methyl-D-aspartate receptor (NMDAR) hypofunction and parvalbumin (PV) neuronal dysfunction leading to disinhibition of mesostriatal dopamine neurons. Here, we test this in a translational mouse imaging study using a ketamine model. Mice were treated with sub-chronic ketamine (30mg/kg) or saline followed byin-vivopositron emission tomography of striatal dopamine synthesis capacity, analogous to measures used in patients. Locomotor activity was measured using the open field test.In-vivocell-type-specific chemogenetic approaches and pharmacological interventions were used to manipulate neuronal excitability. Immunohistochemistry and RNA sequencing were used to investigate molecular mechanisms. Sub-chronic ketamine increased striatal dopamine synthesis capacity (Cohen’s d=2.5,P<0.001)and locomotor activity. These effects were countered by inhibition of midbrain dopamine neurons, and by activation of cortical and ventral subiculum PV interneurons. Sub-chronic ketamine reduced PV expression in these neurons. Pharmacological intervention with SEP-363856, a novel psychotropic agent with agonism at trace amine receptor 1 (TAAR1), significantly reduced the ketamine-induced increase in dopamine synthesis capacity. These results show that sub-chronic ketamine treatment in mice mimics the dopaminergic alterations in patients with psychosis, and suggest an underlying neurocircuit involving PV interneuron hypofunction in frontal cortex and hippocampus as well as activation of midbrain dopamine neurons. A novel TAAR1 agonist reversed the dopaminergic alterations suggesting a therapeutic mechanism for targeting presynaptic dopamine dysfunction in patients.
Wasting food is disgusting: Evidence from behavioral and neuroimaging study of moral judgment of food-wasting behavior
Authors: Marczak Michalina , Marchewka Artur , Wypych Marek , Misiak Michał , Droździel Dawid , Sorokowski Piotr , Sorokowska Agnieszka 
Published: September 2019

AbstractFood-wasting has a profound negative social and environmental impact. Acknowledging that referring to moral judgment can motivate behavior change, the present study aimed to determine moral intuitions underlying the perception of food-wasting behavior. We developed a set of affective standardized scenarios and we used them to collect behavioral and neuroimaging data. In the main study, 50 participants made moral judgments regarding food-wasting, disgusting, harmful, dishonest, or neutral behaviors presented in these scenarios. We found that wasting food was considered morally wrong and it was associated with moral disgust. Neuroimaging data revealed that food-wasting stimuli elicited an increased activity in structures associated with moral judgment, as well as in regions involved in the processing of moral, but also physical disgust. We discuss our results in the context of the evolutionary significance of food that might have led to seeing food-wasting as a moral transgression.
Mathematical model shows how sleep may affect amyloid β fibrillization
Authors: Hoore Masoud , Khailaie Sahamoddin , Montaseri Ghazal , Mitra Tanmay , Meyer-Hermann Michael 
Published: September 2019

AbstractDeposition of amyloid β (Aβ) fibers in extra-cellular matrix of the brain is a ubiquitous feature associated with several neurodegenerative disorders, especially Alzheimer’s disease (AD). While many of the biological aspects that contribute to the formation of Aβ plaques are well addressed at the intra- and inter-cellular level in short timescales, an understanding of how Aβ fibrillization usually starts to dominate at a longer timescale in spite of the presence of mechanisms dedicated to Aβ clearance, is still lacking. Furthermore, no existing mathematical model integrates the impact of diurnal neural activity as emanated from circadian regulation to predict disease progression due to a disruption in sleep-wake cycle. In this study, we develop a minimal model of Aβ fibrillization to investigate the onset of AD over a long time-scale. Our results suggest that the diseased state is a manifestation of a phase change of the system from soluble Aβ (sAβ) to fibrillar Aβ (fAβ) domination upon surpassing a threshold in the production rate of soluble Aβ. By incorporating the circadian rhythm into our model, we reveal that fAβ accumulation is crucially dependent on the regulation of sleep-wake cycle, thereby indicating the importance of a good sleep hygiene in averting AD onset. We also discuss potential intervention schemes to reduce fAβ accumulation in the brain by modification of the critical sAβ production rate.
Psilocybin exerts distinct effects on resting state networks associated with serotonin and dopamine in mice
Authors: Grandjean Joanes , Buehlmann David , Buerge Michaela , Sigrist Hannes , Seifritz Erich , Vollenweider Franz X. , Pryce Christopher R. , Rudin Markus 
Published: September 2019

AbstractHallucinogenic agents have been proposed as potent antidepressants; this includes the serotonin (5-HT) receptor 2A agonist psilocybin. In human subjects, psilocybin alters functional connectivity (FC) within the default-mode network (DMN), a constellation of inter-connected regions that is involved in self-reference and displays altered FC in depressive disorders. In this study we investigated the effects of psilocybin on FC in the analogue of the DMN in mouse, with a view to establishing an experimental animal model to investigate underlying mechanisms. Psilocybin effects were investigated in lightly-anaesthetized mice using resting-state fMRI. Dual-regression analysis identified reduced FC within the ventral striatum in psilocybin-relative to vehicle-treated mice. Refinement of the analysis using spatial references derived from both gene expression maps and viral tracer projection fields revealed two distinct effects of psilocybin: it increased FC between 5-HT-associated networks and elements of the murine DMN, thalamus, and midbrain; it decreased FC within dopamine (DA)-associated striatal networks. These results suggest that interaction between 5-HT- and DA-regulated neural networks contributes to the neural and therefore psychological effects of psilocybin. Furthermore, they highlight how information on molecular expression patterns and structural connectivity can assist in the interpretation of pharmaco-fMRI findings.
SMN-primed ribosomes modulate the translation of transcripts related to Spinal Muscular Atrophy
Authors: Lauria F , Bernabò P , Tebaldi T , Groen EJN , Perenthaler E , Clamer M , Maniscalco F , Marchioretto M , Orri Julia , Dalla Serra M , Inga A , Quattrone A , Gillingwater TH , Viero G 
Published: September 2019

AbstractThe contribution of ribosome heterogeneity and ribosome-associated factors to the molecular control of proteomes in health and disease remains enigmatic. We demonstrate that Survival Motor Neuron (SMN) protein, loss of which causes the neuromuscular disease spinal muscular atrophy (SMA), binds to ribosomes and that this interaction is tissue-dependent. SMN-primed ribosomes are positioned within the first five codons of a set of mRNAs which are enriched in IRES-like sequences in the 5’UTR and rare codons at the beginning of their coding sequence. Loss of SMN at early-stages of SMA induces translational defectsin vivo,characterized by ribosome depletion in rare codons at the third and fifth position of the coding sequence. These positional defects cause ribosome depletion from mRNAs bound by SMN-primed ribosomes and translational impairment of proteins involved in motor neuron function and stability, including acetylcholinesterase. Thus, SMN plays a crucial role in the regulation of ribosome fluxes along mRNAs which encode proteins relevant to SMA pathogenesis.