bluuebunny/crossref_metadata_2025_split huggingface dataset:
Out of hospital cardiac arrests in the Gulf Region: a scoping review
Authors: Batt Alan M. , Lanos Chelsea , Delport Shannon , Al-Hasan Dalal , Knox Shane , Alhmoudi Assim , Anderson Megan , Fares Saleh , Cummins Fergal H. 
Published: December 2019

AbstractBackgroundOut-of-hospital cardiac arrest (OHCA) is a major cause of mortality worldwide. Recent studies demonstrated low survival rates in Middle Eastern countries. Anecdotally there are unique demographic, cultural and logistical challenges in this region. However, there remains a paucity of data published on OHCA in the Middle East. In order to address OHCA in a meaningful manner in the region, we first need to quantify the issue.MethodsWe conducted a scoping review of published and grey literature on OHCA in the Gulf Cooperative Council region that utilised Arksey and O’Malley’s framework. Electronic databases and grey literature sources were identified and searched. Subject matter experts in the region were consulted. All types of studies in English and Arabic were included.ResultsA total of 24 studies were included from Saudi Arabia, the UAE, Oman, Kuwait, and Qatar. No literature was identified from the state of Bahrain. OHCA victims in the region are younger, predominantly male, and more co-morbid than other international studies. We observed low Emergency Medical Service utilisation, low bystander cardiopulmonary resuscitation, return of spontaneous circulation, and survival to discharge rates across the region. There are differences in characteristics of OHCA among ethnic groups.Discussion and conclusionsWe identified unique characteristics associated with OHCA in the region, variances in processes and outcomes, and a lack of coordinated effort to research and address OHCA. We recommend creating lead agencies responsible for coordinating and developing strategies such as community response, public education, and reporting databases.
Kinship and social organization in Copper Age Europe. A cross-disciplinary analysis of archaeology, DNA, isotopes, and anthropology from two Bell Beaker cemeteries
Authors: Sjögren Karl-Göran , Olalde Inigo , Carver Sophie , Allentoft Morten E. , Knowles Tim , Kroonen Guus , Pike Alistair W.G. , Schröter Peter , Brown Keri A. , Robson-Brown Kate , Harrison Richard J. , Bertemes Francois , Reich David , Kristiansen Kristian , Heyd Volker 
Published: December 2019

AbstractWe present a high-resolution cross-disciplinary analysis of kinship structure and social institutions in two Late Copper Age Bell Beaker culture cemeteries of South Germany containing 24 and 18 burials, of which 34 provided genetic information. By combining archaeological, anthropological, genetic and isotopic evidence we are able to document the internal kinship and residency structure of the cemeteries and the socially organizing principles of these local communities. The buried individuals represent four to six generations of two family groups, one nuclear family at the Alburg cemetery, and one seemingly more extended at Irlbach. While likely monogamous, they practiced exogamy, as six out of eight non-locals are women. Maternal genetic diversity is high with 23 different mitochondrial haplotypes from 34 individuals, whereas all males belong to one single Y-chromosome haplogroup without any detectable contribution from Y-chromosomes typical of the farmers who had been the sole inhabitants of the region hundreds of years before. This provides evidence for the society being patrilocal, perhaps as a way of protecting property among the male line, while in-marriage from many different places secured social and political networks and prevented inbreeding. We also find evidence that the communities practiced selection for which of their children (aged 0-14 years) received a proper burial, as buried juveniles were in all but one case boys, suggesting the priority of young males in the cemeteries. This is plausibly linked to the exchange of foster children as part of an expansionist kinship system which is well attested from later Indo-European-speaking cultural groups.
The experimentally obtained functional impact assessments of GT>GC 5’ splice site variants differ markedly from those predicted
Authors: Chen Jian-Min , Lin Jin-Huan , Masson Emmanuelle , Liao Zhuan , Férec Claude , Cooper David N. , Hayden Matthew 
Published: December 2019

ABSTRACTGT>GC 5’ splice site (or +2T>C) variants have been frequently reported to cause human genetic disease. However, although we have demonstrated that GT>GC variants in human disease genes may not invariably be pathogenic, none of the currently available splicing prediction tools appear to be capable of reliably distinguishing those GT>GC variants that generate wild-type transcripts from those that do not. Recently, SpliceAI, a novel deep residual neural network tool, has been developed for splicing prediction. Methodologically distinct from previous approaches that either rely on human-engineered features and/or which focus on short nucleotide windows adjoining exon-intron boundaries, SpliceAI assesses splicing determinants by evaluating 10,000 nucleotides of flanking contextual sequence to predict the functional role in splicing of each position in the pre-mRNA transcript. Herein, we evaluated the performance of SpliceAI in the context of three datasets of GT>GC variants, all of which had been characterized functionally in terms of their impact on mRNA splicing. The first two datasets refer to our recently described “in vivo” dataset of 45 disease-causing GT>GC variants and the “in vitro” dataset of 103 GT>GC substitutions. The third dataset comprised 12 BRCA1 GT>GC variants that were recently analyzed by saturation genome editing. We processed all GT>GC variants using the default settings of SpliceAI. Comparison of the SpliceAI-predicted and experimentally obtained functional impact assessments of the analyzed GT>GC variants revealed that although SpliceAI performed rather better than other prediction tools, it was still far from perfect. A key issue is that the impact of GT>GC (as well as GT>GA or +2T>A) variants that generated wild-type transcripts represents a quantitative change that can vary from barely detectable to almost full expression of wild-type transcripts, with wild-type transcripts often co-existing with aberrantly spliced transcripts. Our findings highlight the challenges that we still face in attempting to accurately identify splice-altering variants.
A Highly-ordered and Fail-safe Electrical Network in Cable Bacteria
Authors: Thiruvallur Eachambadi Raghavendran , Bonné Robin , Cornelissen Rob , Hidalgo-Martinez Silvia , Vangronsveld Jaco , Meysman Filip J. R. , Valcke Roland , Cleuren Bart , Manca Jean V. 
Published: December 2019

AbstractCable Bacteria are an emerging class of electroactive organisms that sustain unprecedented long-range electron transport across centimeter-scale distances. The pathways of the electrical currents in these filamentous microorganisms remain unresolved. Here, the electrical circuitry in a single cable bacterium is visualized with nanoscopic resolution using Conductive Atomic Force Microscopy. Combined with perturbation experiments, it is demonstrated that electrical currents are conveyed through a parallel network of conductive fibers embedded in the cell envelope which are electrically interconnected between adjacent cells. This redundant structural organization of electrical pathways likely forms a crucial adaptive trait for organisms capable of long-distance electron transport. The observed electrical circuit architecture is unique in biology and could inspire future technological applications in bioelectronics.
A proximity-labeling proteomic approach to investigate invadopodia molecular landscape in breast cancer cells
Authors: Thuault Sylvie , Mamelonet Claire , Salameh Joëlle , Ostacolo Kevin , Chanez Brice , Salaün Danièle , Baudelet Emilie , Audebert Stéphane , Camoin Luc , Badache Ali 
Published: December 2019

ABSTRACTMetastatic progression is the leading cause of mortality in breast cancer. Invasive tumor cells develop invadopodia to travel through basement membranes and the interstitial matrix. Substantial efforts have been made to characterize invadopodia molecular composition. However, their full molecular identity is still missing due to the difficulty in isolating them. To fill this gap, we developed a non-hypothesis driven proteomic approach based on the BioID proximity biotinylation technology, using the invadopodia-specific protein Tks5α fused to the promiscuous biotin ligase BirA* as bait. In invasive breast cancer cells, Tks5α fusion concentrated to invadopodia and selectively biotinylated invadopodia components, in contrast to a fusion which lacked the membrane-targeting PX domain (Tks5β). Biotinylated proteins were isolated by affinity capture and identified by mass spectrometry. We identified known invadopodia components, revealing the pertinence of our strategy. Furthermore, we observed that Tks5 newly identified close neighbors belonged to a biologically relevant network centered on actin cytoskeleton organization. Analysis of Tks5β interactome demonstrated that some partners bound Tks5 before its recruitment to invadopodia. Thus, the present strategy allowed us to identify novel Tks5 partners that were not identified by traditional approaches and could help get a more comprehensive picture of invadopodia molecular landscape.
Effective potential reveals evolutionary trajectories in complex fitness landscapes
Authors: Smerlak Matteo 
Published: December 2019

AbstractGrowing efforts to measure fitness landscapes in molecular and microbial systems are premised on a tight relationship between landscape topography and evolutionary trajectories. This relationship, however, is far from being straightforward: depending on their mutation rate, Darwinian populations can climb the closest fitness peak (survival of the fittest), settle in lower regions with higher mutational robustness (survival of the flattest), or fail to adapt altogether (error catastrophes). These bifurcations highlight that evolution does not necessarily drive populations “from lower peak to higher peak”, as Wright imagined. The problem therefore remains: how exactly does a complex landscape topography constrain evolution, and can we predict where it will go next? Here I introduce a generalization of quasispecies theory which identifies metastable evolutionary states as minima of an effective potential. From this representation I derive a coarse-grained, Markov state model of evolution, which in turn forms a basis for evolutionary predictions across a wide range of mutation rates. Because the effective potential is related to the ground state of a quantum Hamiltonian, my approach could stimulate fruitful interactions between evolutionary dynamics and quantum many-body theory.SIGNIFICANCE STATEMENTThe course of evolution is determined by the relationship between heritable types and their adaptive values, the fitness landscape. Thanks to the explosive development of sequencing technologies, fitness landscapes have now been measured in a diversity of systems from molecules to micro-organisms. How can we turn these data into evolutionary predictions? I show that preferred evolutionary trajectories are revealed when the effects of selection and mutations are blended in a single effective evolutionary force. With this reformulation, the dynamics of selection and mutation becomes Markovian, bringing a wealth of classical visualization and analysis tools to bear on evolutionary dynamics. Among these is a coarse-graining of evolutionary dynamics along its metastable states which greatly reduces the complexity of the prediction problem.
Evaluation of MALDI-ToF Mass Spectrometry for Rapid Detection of Cereulide from Bacillus cereus Cultures
Authors: Doellinger Joerg , Schneider Andy , Stark Timo , Ehling-Schulz Monika , Lasch Peter 
Published: December 2019

1.AbstractBacillus cereus plays an often unrecognized role in food borne diseases. Food poisoning caused by this pathogen is manifested by either diarrhea or emesis. While different enterotoxins have been linked to the diarrheal type of B. cereus infections, the emetic toxin cereulide is responsible for the second type. Due to the relatively high prevalence of cereulide associated food poisoning, methods for simple and reliable detection of cereulide producing strains are of utmost importance. Currently, liquid-chromatography coupled to mass spectrometry (LC-MS) is used for sensitive, specific and quantitative cereulide detection, but this technique requires specialized LC-MS equipment, which is often not available in microbiology routine diagnostic laboratories.The last decade has witnessed the advent of matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-ToF MS) as a simple, rapid and cost-efficient technique for identification of microbial pathogens in routine diagnostics. Just recently, two different studies reported on the application of MALDI-ToF MS for either the differentiation of emetic and non-emetic strains of B. cereus or for direct detection of cereulide from bacterial colony smears. However, no method evaluation and optimization was performed in frame of these studies. Thus, additional investigations on the selectivity and sensitivity of MALDI-TOF MS for cereulide detection are needed before implementation of this method in routine diagnostics can be considered. These aspects prompted us to investigate open or controversial issues and to systematically test sample preparation methods, commonly used for microbial identification for their suitability to detect the emetic toxin directly from bacteria.Based on our experimental findings we propose a MALDI-ToF MS workflow that allows identification of B. cereus and sensitive detection of cereulide in parallel, using standard, linear-mode MALDI-ToF MS equipment. The experimental protocol is based on the well-established ethanol/formic acid extraction method and offers, if required, possibilities for further characterization by more sophisticated LC-MS-based methods. In summary, the ease of use and the achieved level of analytical sensitivity as well as the wide-spread availability of standard MALDI-ToF MS equipment in clinical microbiological laboratories provides a promising tool to improve and to facilitate routine diagnostics of B. cereus associated food intoxications.
Alcohol intake triggers aberrant synaptic pruning leading to synapse loss and anxiety-like behavior
Authors: Socodato Renato , Henriques Joana F. , Portugal Camila C. , Almeida Tiago O. , Tedim-Moreira Joana , Alves Renata L. , Canedo Teresa , Silva Cátia , Magalhães Ana , Summavielle Teresa , Relvas João B. 
Published: December 2019

AbstractAlcohol use adversely impacts the life of millions of people worldwide. Deficits in synaptic transmission and in microglial function are common findings in human alcohol users and in animal models of alcohol intoxication. Here, we show that alcohol intake over ten consecutive days resulted in substantial loss of excitatory synapse in the prefrontal cortex, a consequence of aberrant synaptic pruning, which led to increased anxiety-like behavior. Mechanistically, these effects of alcohol intake were mediated by a detrimental increase of microglia engulfment capacity via Src-dependent activation of NFkB and consequent TNF production. Accordingly, pharmacological blockade of Src activation or TNF production by microglia, genetic ablation of TNF, or diphtheria toxin-mediated conditional ablation of microglia attenuated aberrant synaptic pruning preventing excitatory synapse loss and anxiety-like behavior. Overall, our data suggest that aberrant pruning of excitatory synapses by microglia might disrupt synaptic transmission during alcohol use.
A mean-field approach to the dynamics of networks of complex neurons, from nonlinear Integrate-and-Fire to Hodgkin-Huxley models
Authors: Carlu M. , Chehab O. , Dalla Porta L. , Depannemaecker D. , Héricé C. , Jedynak M. , Köksal Ersöz E. , Muratore P. , Souihel S. , Capone C. , Zerlaut Y. , Destexhe A. , di Volo M. 
Published: December 2019

AbstractWe present a mean-field formalism able to predict the collective dynamics of large networks of conductance-based interacting spiking neurons. We apply this formalism to several neuronal models, from the simplest Adaptive Exponential Integrate-and-Fire model to the more complex Hodgkin-Huxley and Morris-Lecar models. We show that the resulting mean-field models are capable of predicting the correct spontaneous activity of both excitatory and inhibitory neurons in asynchronous irregular regimes, typical of cortical dynamics. Moreover, it is possible to quantitatively predict the populations response to external stimuli in the form of external spike trains. This mean-field formalism therefore provides a paradigm to bridge the scale between population dynamics and the microscopic complexity of the individual cells physiology.NEW & NOTEWORTHYPopulation models are a powerful mathematical tool to study the dynamics of neuronal networks and to simulate the brain at macroscopic scales. We present a mean-field model capable of quantitatively predicting the temporal dynamics of a network of complex spiking neuronal models, from Integrate-and-Fire to Hodgkin-Huxley, thus linking population models to neurons electrophysiology. This opens a perspective on generating biologically realistic mean-field models from electrophysiological recordings.
Extrinsic Activin signaling cooperates with an intrinsic temporal program to increase mushroom body neuronal diversity
Authors: Rossi Anthony M. , Desplan Claude 
Published: December 2019

SummaryTemporal patterning of neural progenitors leads to the sequential production of diverse neuronal types. To better understand how extrinsic cues interact with intrinsic temporal programs to contribute to temporal patterning, we studied theDrosophilamushroom body neural progenitors (neuroblasts). Each of these four neuroblasts divides ~250 times to sequentially produce only three main neuronal types over the course of ~9 days of development: γ, followed by α’β’, and finally αβ neurons. The intrinsic temporal clock is composed of two RNA-binding proteins, IGF-II mRNA binding protein (Imp) and Syncrip (Syp), that are expressed in opposing temporal gradients. Activin signaling affects the production of α’β’ neurons but whether and how this extrinsic cue interacts with the intrinsic temporal program was not known. We show that the Activin ligand Myoglianin produced from glia regulates the levels of the intrinsic temporal factor Imp in mushroom body neuroblasts. In neuroblasts mutant for the Activin signaling receptorbaboon,Imp levels are higher than normal during the α’β’ temporal window, leading to the specific loss of the α’β’ neurons. The intrinsic temporal clock still progresses but with a delay, skipping the α’β’ window without affecting the total number of neurons produced: The number of γ neurons increases, α’β’ disappear and the number of αβ neurons decreases. Our results illustrate that an extrinsic cue modifies an intrinsic temporal program to increase neuronal diversity.
Hierarchical assembly of the MLL1 core complex within a biomolecular condensate regulates H3K4 methylation
Authors: Namitz Kevin E.W. , Tan Song , Cosgrove Michael S. 
Published: December 2019

ABSTRACTThe enzymes that regulate histone H3 lysine 4 (H3K4) methylation are required for cellular differentiation and development and are often mutated in human disease. Mixed Lineage Leukemia protein-1 (MLL1) is a member of the SET1 family of histone H3 lysine 4 methyltransferases, which require interaction with a conserved sub-complex consisting ofWDR5,RbBP5,Ash2L andDPY30 (WRAD2) for maximal activity. It is currently unclear how assembly of SET1 family complexes is involved in the spatiotemporal control of H3K4 methylation in eukaryotic genomes. In this investigation, we systematically characterized the hydrodynamic and kinetic properties of a reconstituted human MLL1 core complex and found that its assembly is highly concentration and temperature dependent. Consistent with a hierarchical assembly pathway, we found that the holo-complex assembles through interactions between the MW and RAD2sub-complexes, which is correlated with enzymatic activity. Surprisingly, we found that the disassembled state is favored at physiological temperatures, and that this thermodynamic barrier can be overcome under conditions that induce high-local concentrations of subunits in phase separated compartments. Combining this data with the observation that MLL1 primary sequence contains large regions of intrinsic disorder, we propose a “swinging-domain” model in which the interaction between a tethered MW subcomplex and multiple nucleosome-RAD2complexes is regulated by the rapid formation or dissolution of biomolecular condensates, such as occurs in transcription factories. This model provides an elegant “switch-like” mechanism for spatiotemporal control of H3K4 methylation within eukaryotic genomes.
Spatially Varying Trophic Effects of Reservoir-Derived Plankton on Stream Macroinvertebrates Among Heterogeneous Habitats Within Reaches
Authors: Takahashi Shinji , Takemon Yasuhiro , Omura Tatsuo , Watanabe Kozo 
Published: December 2019

SummaryDam reservoirs often supply high amounts of plankton to downstream reaches, leading to a critical shift of trophic origins of stream ecosystems from natural sources (e.g. attached algae and terrestrial inputs) to reservoir-oriented plankton. Although this is a widely observed phenomenon, previous studies focused only on lotic habitats (e.g. riffles) rather than lentic habitats such as backwaters and isolated ponds (IP).Using a stable isotope three-source mixing model, we evaluated trophic contributions of reservoir-derived plankton, epilithon and terrestrial leaves to stream macroinvertebrates at four dam outlet reaches and two reference reaches in the Natori River catchment, Japan. We compared four different habitat types co-occurring within the reaches: lotic habitat (riffle and pool), bar-head (BH) lentic habitat, bar-tail (BT) lentic habitat (backwater) and isolated pond (IP) on sandy bars.The trophic contributions of reservoir-derived plankton were significantly lower in lentic habitats (BH, 15.4%; BT, 10.4%; IP, 9.1%) than in lotic habitats (mean, 27.7%). This was especially notable for filter feeders that feed on suspended fine particulate organic matter (SFPOM). The three-source model analysis indicated a lower biomass proportion of dam plankton in lentic SFPOM (mean, 21.2%) than in lotic SFPOM (mean, 35.6%). This difference in SFPOM composition was reflected in the lower trophic contribution of dam plankton to lentic filter feeders.The abundance ratio of filter feeders in the community was decreased in lentic habitats, while the abundance ratios of collector-gatherers, scrapers and shredders were increased. Macroinvertebrates in lentic habitats fed on sources less mixed with reservoir-derived plankton (e.g. benthic coarse particulate organic matter [BCPOM], benthic fine particulate organic matter [BFPOM] and epilithon); therefore, the trophic impact of reservoirs was indistinctive at the community level, indicating that lentic habitats can function as trophic refugia to mitigate the trophic impact of reservoirs.Because lentic habitats were decreased in area (accounting for 5.7% of average total area) in the downstream reaches of dams due to riverbed degradation, lentic habitats must be created in order to restore the trophic impact of reservoirs in river ecosystems.