bluuebunny/crossref_metadata_2025_split huggingface dataset:
WISDOM project – V. Resolving molecular gas in Keplerian rotation around the supermassive black hole in NGC 0383
Authors: North Eve V , Davis Timothy A , Bureau Martin , Cappellari Michele , Iguchi Satoru , Liu Lijie , Onishi Kyoko , Sarzi Marc , Smith Mark D , Williams Thomas G 
Published: September 2019

ABSTRACT
As part of the mm-Wave Interferometric Survey of Dark Object Masses (WISDOM), we present a measurement of the mass of the supermassive black hole (SMBH) in the nearby early-type galaxy NGC 0383 (radio source 3C 031). This measurement is based on Atacama Large Millimeter/sub-millimeter Array (ALMA) cycle 4 and 5 observations of the 12CO(2–1) emission line with a spatial resolution of 58 × 32 pc2 (0.18 arcsec × 0.1 arcsec). This resolution, combined with a channel width of 10 km s−1, allows us to well resolve the radius of the black hole sphere of influence (measured as RSOI = 316 pc  =  0.98 arcsec), where we detect a clear Keplerian increase of the rotation velocities. NGC 0383 has a kinematically relaxed, smooth nuclear molecular gas disc with weak ring/spiral features. We forward model the ALMA data cube with the Kinematic Molecular Simulation (KinMS) tool and a Bayesian Markov Chain Monte Carlo method to measure an SMBH mass of (4.2 ± 0.7) × 109 M⊙, a F160W-band stellar mass-to-light ratio that varies from 2.8 ± 0.6 M⊙/L$_{\odot ,\, \mathrm{F160W}}$ in the centre to 2.4 ± 0.3 M⊙$/\rm L_{\odot ,\, \mathrm{F160W}}$ at the outer edge of the disc and a molecular gas velocity dispersion of 8.3 ± 2.1 km s−1(all 3σ uncertainties). We also detect unresolved continuum emission across the full bandwidth, consistent with synchrotron emission from an active galactic nucleus. This work demonstrates that low-J CO emission can resolve gas very close to the SMBH ($\approx 140\, 000$ Schwarzschild radii) and hence that the molecular gas method is highly complimentary to megamaser observations, as it can probe the same emitting material.
How to add massive neutrinos to your ΛCDM simulation – extending cosmology rescaling algorithms
Authors: Zennaro Matteo , Angulo Raúl E , Aricò Giovanni , Contreras Sergio , Pellejero-Ibáñez Marcos 
Published: September 2019

ABSTRACT
Providing accurate predictions for the spatial distribution of matter and luminous tracers in the presence of massive neutrinos is an important task, given the imminent arrival of highly accurate large-scale structure observations. In this work, we address this challenge by extending cosmology-rescaling algorithms to massive neutrino cosmologies. In this way, a ΛCDM simulation can be modified to provide non-linear structure formation predictions in the presence of a hot component of arbitrary mass, and, if desired, to include non-gravitational modifications to the clustering of matter on large scales. We test the accuracy of the method by comparing its predictions to a suite of simulations carried out explicitly including a neutrino component in its evolution equations. We find that, for neutrino masses in the range Mν ∈ [0.06, 0.3] eV the matter power spectrum is recovered to better than $1{{\ \rm per\ cent}}$ on all scales k < 2 h Mpc−1. Similarly, the halo mass function is predicted at a few per cent level over the range Mhalo ∈ [1012, 1015] h−1 M⊙, and so do also the multipoles of the galaxy two-point correlation function in redshift space over r ∈ [0.1, 200] h−1 Mpc. We provide parametric forms for the necessary transformations, as a function of Ωm and Ων for various target redshifts.
The Genetic Background Modulates the Evolution of Fluoroquinolone-Resistance in Mycobacterium tuberculosis
Authors: Castro Rhastin A D , Ross Amanda , Kamwela Lujeko , Reinhard Miriam , Loiseau Chloé , Feldmann Julia , Borrell Sonia , Trauner Andrej , Gagneux Sebastien 
Published: September 2019

AbstractFluoroquinolones (FQ) form the backbone in experimental treatment regimens against drug-susceptible tuberculosis. However, little is known on whether the genetic variation present in natural populations of Mycobacterium tuberculosis (Mtb) affects the evolution of FQ-resistance (FQ-R). To investigate this question, we used nine genetically distinct drug-susceptible clinical isolates of Mtb and measured their frequency of resistance to the FQ ofloxacin (OFX) in vitro. We found that the Mtb genetic background led to differences in the frequency of OFX-resistance (OFX-R) that spanned two orders of magnitude and substantially modulated the observed mutational profiles for OFX-R. Further, in vitro assays showed that the genetic background also influenced the minimum inhibitory concentration and the fitness effect conferred by a given OFX-R mutation. To test the clinical relevance of our in vitro work, we surveyed the mutational profile for FQ-R in publicly available genomic sequences from clinical Mtb isolates, and found substantial Mtb lineage-dependent variability. Comparison of the clinical and the in vitro mutational profiles for FQ-R showed that 51% and 39% of the variability in the clinical frequency of FQ-R gyrA mutation events in Lineage 2 and Lineage 4 strains, respectively, can be attributed to how Mtb evolves FQ-R in vitro. As the Mtb genetic background strongly influenced the evolution of FQ-R in vitro, we conclude that the genetic background of Mtb also impacts the evolution of FQ-R in the clinic.
OGRDB: a reference database of inferred immune receptor genes
Authors: Lees William , Busse Christian E , Corcoran Martin , Ohlin Mats , Scheepers Cathrine , Matsen Frederick A , Yaari Gur , Watson Corey T ,   The AIRR Community, Collins Andrew , Shepherd Adrian J 
Published: September 2019

Abstract
High-throughput sequencing of the adaptive immune receptor repertoire (AIRR-seq) is providing unprecedented insights into the immune response to disease and into the development of immune disorders. The accurate interpretation of AIRR-seq data depends on the existence of comprehensive germline gene reference sets. Current sets are known to be incomplete and unrepresentative of the degree of polymorphism and diversity in human and animal populations. A key issue is the complexity of the genomic regions in which they lie, which, because of the presence of multiple repeats, insertions and deletions, have not proved tractable with short-read whole genome sequencing. Recently, tools and methods for inferring such gene sequences from AIRR-seq datasets have become available, and a community approach has been developed for the expert review and publication of such inferences. Here, we present OGRDB, the Open Germline Receptor Database (https://ogrdb.airr-community.org), a public resource for the submission, review and publication of previously unknown receptor germline sequences together with supporting evidence.
Disruption of MIR396e and MIR396f improves rice yield under nitrogen-deficient conditions
Authors: Zhang Jinshan , Zhou Zhenyu , Bai Jinjuan , Tao Xiaoping , Wang Ling , Zhang Hui , Zhu Jian-Kang 
Published: September 2019

Abstract
The microRNA miR396 directly represses GROWTH-REGULATING FACTORs (OsGRFs) and has been implicated in regulating rice yield and in nitrogen assimilation. Overexpressing the miR396 targets OsGRF4 and OsGRF6 improves rice yield via increased grain size and panicle branching, respectively. Here, we used CRISPR/Cas9 to assess the function of miR396 genes in rice. Knockout of MIR396ef (MIR396e and MIR396f), but not other isoforms, enhanced both grain size and panicle branching, resulting in increased grain yield. Importantly, under nitrogen-deficient conditions, mir396ef mutants showed an even higher relative increase in grain yield as well as elevated above-ground biomass. Furthermore, we identified OsGRF8 as a new target of miR396, in addition to the known targets OsGRF4 and OsGRF6. Disruption of the miR396-targeting site in OsGRF8 was sufficient to both enlarge grain size and elongate panicles. Our results suggest that rice-seed and panicle development are regulated by miR396ef-GRF4/6/8-GIF1/2/3 modules and that miR396ef are promising targets of genome editing for breeding environmentally friendly rice varieties that require less nitrogen fertilization.
Carceral Spaces and Social Reproduction: Exploring Export Processing Zones in Sri Lanka and Prisons in Argentina
Authors: Pereyra-Iraola Victoria , Gunawardana Samanthi J 
Published: September 2019

AbstractThe article reflects on the ways in which social reproduction intersects with (im)mobility in export-processing zones in Sri Lanka and the outskirts of prisons in Argentina. Framing factories and prisons as “carceral spaces” and drawing upon diverse case study materials, it focuses on (i) the daily circulations and waiting that take place around these closely regulated sites and (ii) the relations of care that emerge in these sites. The article analyzes how gendered care work can be an active form of agency and resistance to structural confinement and violence, which is nevertheless embedded in broader forms of depletion.
Do we know who they are? On the identity of Pholoe (Annelida: Sigalionidae: Pholoinae) species from northern Europe
Authors: Meißner Karin , Götting Miriam , Nygren Arne 
Published: September 2019

AbstractPholoe species described from northern European coastal waters are studied here, based on morphological and molecular methods. We confirm the current taxonomic status of P. assimilis, P. baltica, P. inornata and P. pallida. All species descriptions are reviewed and refined, barcodes are provided allowing the identification of these species based on molecular markers. Expanding morphological methods by using confocal laser scanning microscopy has added new characters to species diagnoses and makes species identification more secure. The reliability of characters traditionally used for identification of Pholoe species is evaluated. The newly presented identification key allows the delimitation of the four species reported for European coastal waters and also includes P. minuta and P. longa. The latter have been originally described from Greenland, but were often reported from European coastal waters. The results of our studies provide new insights into the distribution of the different species. Relationships of Pholoe species from mainly northern European waters are analysed based on molecular mitochondrial and nuclear markers. We stress the need for the prospective development of a precise terminology for prostomial appendages in Pholoe by including fine anatomical studies.
Ongoing revision of Echiniscoididae (Heterotardigrada: Echiniscoidea), with the description of a new interstitial species and genus with unique anal structures
Authors: Møbjerg Nadja , Jørgensen Aslak , Kristensen Reinhardt M 
Published: September 2019

Abstract
Marine tidal heterotardigrades (Echiniscoididae) have gained increasing interest owing to their unique adaptations and evolutionary position, bridging marine and limnoterrestrial taxa. Echiniscoididae was established to accommodate the marine genera Anisonyches and Echiniscoides. However, it has become apparent that Anisonyches, with its claw configuration, median cirrus and seminal receptacles, clearly has little or no affinity to tidal echiniscoidids with supernumerary claws. Consequently, we establish Anisonychidae fam. nov. to accommodate Anisonyches in a paraphyletic Arthrotardigrada and discuss its affinity to other heterotardigrade taxa. We recently split Echiniscoides into Isoechiniscoides and Echiniscoides s.l. The latter remains a miscellany of species complexes and undescribed genera, and it has become evident that a larger number of echiniscoidids belonging to Echiniscoides, Isoechiniscoides and undescribed genera coexist in intertidal sediments. Here, we erect Neoechiniscoides aski gen. nov., sp. nov. from Roscoff, France, which has a unique anal system, characterized by prominent lateral lobes with a set of wing-like structures. Phylogenetic analyses based on COI sequences infer a close relationship between N. aski, an undescribed species from Roscoff and unidentified species from Maine, USA. We propose that the new genus includes the former Echiniscoides species Echiniscoides pollocki and Echiniscoides horningi, which we hereby transfer.
Data-driven discovery of changes in clinical code usage over time: a case-study on changes in cardiovascular disease recording in two English electronic health records databases (2001-2015)
Authors: Rockenschaub Patrick , Nguyen Vincent , Aldridge Rob W. , Acosta Dionisio , García-Gómez Juan M , Sáez Carlos 
Published: September 2019

ABSTRACTObjectivesTo demonstrate how data-driven variability methods can be used to identify changes in disease recording in two English electronic health records databases between 2001-2015.DesignRepeated cross-sectional analysis that applied data-driven temporal variability methods to assess month-by-month changes in routinely-collected medical data. A measure of difference between months was calculated based on joint distributions of age, gender, socio-economic status and recorded cardiovascular diseases. Distances between months were used to identify temporal trends in data recording.Setting400 English primary care practices from the Clinical Practice Research Datalink (CPRD GOLD) and 451 hospital trusts from the Hospital Episode Statistics (HES).Main outcomesThe proportion of patients (CPRD GOLD) and hospital admissions (HES) with a recorded cardiovascular disease (CPRD GOLD: coronary heart disease, heart failure, peripheral arterial disease, stroke; HES: International Classification of Disease ICD codes I20-I69/G45).ResultsBoth databases showed gradual changes in cardiovascular disease recording between 2001 and 2008. The recorded prevalence of included cardiovascular diseases in CPRD GOLD increased by 47%-62%, which partially reversed after 2008. For hospital records in HES, there was a relative decrease in angina pectoris (−34.4%) and unspecified stroke (−42.3%) over the same time period, with a concomitant increase in chronic coronary heart disease (+14.3%). Multiple abrupt changes in the use of myocardial infarction codes in hospital were found in March/April 2010, 2012 and 2014, possibly linked to updates of clinical coding guidelines.ConclusionsIdentified temporal variability could be related to potentially non-medical causes such as updated coding guidelines. These artificial changes may introduce temporal correlation among diagnoses inferred from routine data, violating the assumptions of frequently used statistical methods. Temporal variability measures provided an objective and robust technique to identify, and subsequently account for, those changes in electronic health records studies without any prior knowledge of the data collection process.
Succinylation Links Metabolic Reductions to Amyloid and Tau Pathology
Authors: Yang Yun , Tapias Victor , Acosta Diana , Xu Hui , Chen Huanlian , Bhawal Ruchika , Anderson Elizabeth , Ivanova Elena , Lin Hening , Sagdullaev Botir T. , Klein William L. , Viola Kirsten L. , Gandy Sam , Haroutunian Vahram , Beal M. Flint , Eliezer David , Zhang Sheng , Gibson Gary E. 
Published: September 2019

AbstractAbnormalities in glucose metabolism and misfolded protein deposits composed of the amyloid-β peptide (Aβ) and tau are the three most common neuropathological hallmarks of Alzheimer’s disease (AD), but their relationship(s) to the disease process or to each other largely remains unclear. In this report, the first human brain quantitative lysine succinylome together with a global proteome analysis from controls and patients reveals that lysine succinylation contributes to these three key AD-related pathologies. Succinylation, a newly discovered protein post-translational modification (PTM), of multiple proteins, particularly mitochondrial proteins, declines with the progression of AD. In contrast, amyloid precursor protein (APP) and tau consistently exhibit the largest AD-related increases in succinylation, occurring at specific sites in AD brains but never in controls. Transgenic mouse studies demonstrate that succinylated APP and succinylated tau are detectable in the hippocampus concurrent with Aβ assemblies in the oligomer and insoluble fiber assembly states. Multiple biochemical approaches revealed that succinylation of APP alters APP processing so as to promote Aβ accumulation, while succinylation of tau promotes its aggregation and impairs its microtubule binding ability. Succinylation, therefore, is the first single PTM that can be added in parallel to multiple substrates, thereby promoting amyloidosis, tauopathy, and glucose hypometabolism. These data raise the possibility that, in order to show meaningful clinical benefit, any therapeutic and/or preventative measures destined for success must have an activity to either prevent or reverse the molecular pathologies attributable to excess succinylation.
Network Analysis of Inflammatory Bowel Disease Reveals PTPN2 As New Monogenic Cause of Intestinal Inflammation
Authors: Parlato Marianna , Pazmandi Julia , Nian Qing , Charbit-Henrion Fabienne , Bègue Bernadette , Martin Emmanuel , Thian Marini , Müller Felix , Maggioni Marco , Duclaux-Loras Rémi , Rieux-Laucat Frederic , Molina Thierry-Jo , Latour Sylvain , Ruemmele Frank , Menche Jörg , Rodrigues-Lima Fernando , Boztug Kaan , Cerf-Bensussan Nadine 
Published: September 2019

ABSTRACTBACKGROUND & AIMSGenome-wide association studies (GWAS) have uncovered multiple loci associated with inflammatory bowel disease (IBD), yet delineating functional consequences is complex. We used a network-based approach to uncover traits common to monogenic and polygenic forms of IBD in order to reconstruct disease relevant pathways and prioritize causal genes.METHODSWe have used an iterative random walk with restart to explore network neighborhood around the core monogenic IBD cluster and disease-module cohesion to identify functionally relevant GWAS genes. Whole exome sequencing was used to screen a cohort of monogenic IBD for germline mutations in top GWAS genes. One mutation was identified and validated by a combination of biochemical approaches.RESULTSMonogenic IBD genes clustered siginificantly on the molecular networks and had central roles in network topology. Iterative random walk from these genes allowed to rank the GWAS genes, among which 14 had high disease-module cohesion and were selected as putative causal genes. As a proof of concept, a germline loss of function mutation was identified in PTPN2, one of the top candidates, as a novel genetic etiology of early-onset intestinal autoimmunity. The mutation abolished the catalytic activity of the enzyme, resulting in haploinsufficiency and hyper-activation of the JAK/STAT pathway in lymphocytes.CONCLUSIONSOur network-based approach bridges the gap between large-scale network medicine prediction and single-gene defects and underscores the crucial need of fine tuning the JAK/STAT pathway to preserve intestinal immune homeostasis. Our data provide genetic-based rationale for using drugs targeting the JAK/STAT pathway in IBD.
Time-dependent modulation of spinal excitability during action observation in the macaque monkey
Authors: Jerjian S.J. , Lemon R.N. , Kraskov A. 
Published: September 2019

ABSTRACTNeurons in the primate motor cortex, including identified pyramidal tract neurons projecting to the spinal cord, respond to the observation of others’ actions, yet this does not cause movement in the observer. Here, we investigated changes in spinal excitability during action observation by monitoring short latency electromyographic responses produced by single shocks delivered directly to the pyramidal tract. Responses in hand and digit muscles were recorded from two adult rhesus macaques while they performed, observed or withheld reach-to-grasp and hold actions. We found modest grasp-specific facilitation of hand muscle responses during hand shaping for grasp, which persisted when the grasp was predictable but obscured from the monkey’s vision. We also found evidence of a more general inhibition before observed movement onset, and the size of this inhibition effect was comparable to the inhibition after an explicit NoGo signal. These results confirm that the spinal circuitry controlling hand muscles is modulated during action observation, and this may be driven by internal representations of actions. The relatively modest changes in spinal excitability during observation suggest net corticospinal outflow exerts only minor, sub-threshold changes on hand motoneuron pools, thereby preventing any overflow of mirror activity into overt movement.
Efferent Modulation of Spontaneous Lateral Line Activity During and after Zebrafish Motor Commands
Authors: Lunsford Elias T. , Skandalis Dimitri A. , Liao James C. 
Published: September 2019

AbstractAccurate sensory processing during movement requires the animal to distinguish between external (exafferent) and self-generated (reafferent) stimuli to maintain sensitivity to biologically relevant cues. The lateral line system in fishes is a mechanosensory organ that experiences reafferent sensory feedback via detection of fluid motion relative to the body generated during behaviors such as swimming. For the first time in larval zebrafish (Danio rerio), we employed simultaneous recordings of lateral line and motor activity to reveal the activity of afferent neurons arising from endogenous feedback from hindbrain efferent neurons during locomotion. Frequency of spontaneous spiking in posterior lateral line afferent neurons decreased during motor activity and was absent for more than half of swimming trials. Targeted photoablation of efferent neurons abolished the afferent inhibition that was correlated to swimming, indicating that inhibitory efferent neurons are necessary for modulating lateral line sensitivity during locomotion. We monitored calcium activity with Tg(elav13:GCaMP6s) fish and found synchronous activity between putative cholinergic efferent neurons and motor neurons. We examined correlates of motor activity to determine which may best predict the attenuation of afferent activity and therefore what components of the motor signal are translated through the corollary discharge. Swim duration was most strongly correlated to the change in afferent spike frequency. Attenuated spike frequency persisted past the end of the fictive swim bout, suggesting that corollary discharge also affects the glide phase of burst and glide locomotion. The duration of the glide in which spike frequency was attenuated increased with swim duration but decreased with motor frequency. Our results detail a neuromodulatory mechanism in larval zebrafish that adaptively filters self-generated flow stimuli during both the active and passive phases of locomotion.
Cerebellar Purkinje cell microcircuits are essential for tremor
Authors: Brown Amanda M , White Joshua J , van der Heijden Meike E , Lin Tao , Sillitoe Roy V 
Published: September 2019

AbstractTremor is currently ranked as the most common movement disorder. The brain regions and neural signals that initiate the debilitating shakiness of different body parts remain unclear. Here, we found that genetically silencing cerebellar Purkinje cell activity blocked tremor in mice that were given the tremorgenic drug harmaline. We show in awake behaving mice that the onset of tremor is coincident with rhythmic Purkinje cell firing, which alters the output of their target cerebellar nuclei cells. We mimic the tremorgenic action of the drug with optogenetics and present evidence that highly patterned Purkinje cell activity drives a powerful tremor in otherwise normal mice. Modulating the altered activity with deep brain stimulation directed to the Purkinje cell output in the cerebellar nuclei reduced tremor in freely moving mice. Together, the data implicate Purkinje cell connectivity as a neural substrate for tremor and a gateway for signals that mediate the disease.