bluuebunny/crossref_metadata_2025_split huggingface dataset:
SNP calling for the Illumina Infinium Omni5-4 SNP BeadChip kit using the butterfly method
Authors: Andersen Mikkel Meyer , Christiansen Steffan Noe , Andersen Jeppe Dyrberg , Eriksen Poul Svante , Morling Niels 
Published: January 2022

AbstractWe introduce the “butterfly method” for SNP calling with the Illumina Infinium Omni5-4 BeadChip kit without the use of Illumina GenomeStudio software. The method is a within-sample method and does not use other samples nor population frequencies to call SNPs. The butterfly method is based on a three-component mixture of normal distributions, in which parameters are easily found using the open-source statistical software R. This makes the method transparent, straight-forward to change parameters according to the user’s needs, and easy to analyse the data within R after the SNPs have been called. We contribute with two open-source R packages that make SNP calling easy by helping with bookkeeping and by giving easy access to meta-information about the SNPs on the Illumina Infinium Omni5-4 BeadChip Kit (including chromosome, probe type, and SNP bases). We test our method on > 4 mio. SNPs and compare the results with those obtained with the GenTrain method used by Illumina GenomeStudio as well as SNPs obtained by PCR-free whole genome sequencing (WGS). We demonstrate two variants of our method: one where we account for potential probe type bias by estimating a separate model for each probe type (type I and type II) and another that uses a general model such that the model’s parameter estimates do not depend on the sample that is being analysed. We focused on varying the no-call rate and show how it changed the concordance with that of WGS. This is done by using a threshold on the a posteriori probability of belonging to a SNP cluster and by using the number of beads to adjust the stringency of the no-call mechanism. With the butterfly method, we achieve a SNP call rate of around 99% and a SNP concordance of around 99% with the WGS data. By lowering the a posteriori probability threshold for no-calls, we can get a higher call rate fraction than the GenomeStudio and by using a higher a posteriori probability threshold, we can achieve a higher concordance with the WGS data than the GenomeStudio.
Fat2 polarizes the WAVE complex in trans to align cell protrusions for collective migration
Authors: Williams Audrey M. , Donoughe Seth , Munro Edwin , Horne-Badovinac Sally 
Published: January 2022

AbstractFor a group of cells to migrate together, each cell must couple the polarity of its migratory machinery with that of the other cells in the cohort. Although collective cell migrations are common in animal development, little is known about how protrusions are coherently polarized among groups of migrating epithelial cells. We address this problem in the collective migration of the follicular epithelial cells in Drosophila melanogaster. In this epithelium, the cadherin Fat2 localizes to the trailing edge of each cell and promotes the formation of lamellipodia at the leading edge of the cell behind. We show that Fat2 performs this function by acting in trans to restrict WAVE complex activity to one long-lived region along each cell’s leading edge. Without Fat2, the WAVE complex distribution expands around the cell perimeter and fluctuates over time, resulting in reduced, unpolarized protrusive activity. We further show that Fat2’s influence is very local, with sub-micron-scale puncta of Fat2 concentrating the WAVE complex in corresponding puncta just across the leading-trailing cell-cell interface. These findings demonstrate that a trans interaction between Fat2 and the WAVE complex creates stable regions of protrusive activity in each cell and aligns the cells’ protrusions across the epithelium for directionally persistent collective migration.
Increased early sodium current causes familial atrial fibrillation and dampens effect of flecainide
Authors: O’Reilly M , Sommerfeld LC , O’Shea C , Broadway-Stringer S , Andaleeb S , Reyat JS , Kabir SN , Stastny D , Malinova A , Delbue D , Fortmueller L , Gehmlich K , Pavlovic D , Skryabin BV , Holmes AP , Kirchhof P , Fabritz L 
Published: January 2022

Abstract(1)AimsAtrial fibrillation (AF) is the most common cardiac arrhythmia. Pathogenic variants in genes encoding ion channels are associated with familial AF. The point mutation M1875T in the SCN5A gene, which encodes the α-subunit of the cardiac sodium channel Nav1.5, has been associated with increased atrial excitability and familial AF.(2)MethodsWe designed a new murine model carrying the Scn5a-M1875T mutation enabling us to study the effects of the Nav1.5 mutation in detail in vivo and in vitro using patch clamp and microelectrode recording of atrial cardiomyocytes, optical mapping, ECG, echocardiography, gravimetry, histology and biochemistry.(3)ResultsAtrial cardiomyocytes from newly generated adult Scn5a-M1875T+/- mice showed a selective increase in the early (peak) cardiac sodium current, larger action potential amplitude and a faster peak upstroke velocity. Conduction slowing caused by the sodium channel blocker flecainide was less pronounced in Scn5a-M1875T+/- compared to wildtype atria. Overt hypertrophy or heart failure in Scn5a-M1875T+/- mice could be excluded.(4)ConclusionThe Scn5a-M1875T point mutation causes gain-of-function of the cardiac sodium channel. Our results suggest increased atrial peak sodium current as a potential trigger for increased atrial excitability and thus AF.What’s newThe point mutation M1875T in the C-terminal domain of the cardiac sodium channel Nav1.5 causes an increase in early peak sodium current in left atria.The observed changes induced by this point mutation suggest an increase in peak sodium current as a cause of familial atrial fibrillation (AF).Our findings provide a possible explanation for the variable effectiveness of sodium channel blockers in patients with AF. Carriers of such sodium channel gain-of-function mutations may benefit more from tailored treatments.Graphical abstract
pyNeurode: a real-time neural signal processing framework
Authors: Tam Wing-kin , Nolan Matthew F. 
Published: January 2022

AbstractAccurate decoding of neural signals often requires assigning extracellular waveforms acquired on the same electrode to their originating neurons, a process known as spike sorting. While many offline sorters are available, accurate online sorting of spikes with many channels is still a challenging problem. Existing online sorters either use simple algorithms with low accuracy, can only process a handful of channels, or depend on a complex runtime environment that is difficult to set up. We have developed a state-of-the-art online spike sorting platform in Python that enables large-scale, fully automatic real-time spike sorting and decoding on hundreds of channels. Our system is cross-platform and works seamlessly with the Open Ephys suite of open-source hardware and software widely used in many neuroscience laboratories worldwide. It also comes with a user-friendly graphical user interface to monitor the cluster quality, spike waveforms and neuronal firing rate. Our platform has comparable accuracy to offline sorters and can achieve an end-to-end sorting latency of around 160 ms for 128-channel signals. It will be useful for research in fundamental neuroscience, closed-loop feedback neuromodulation and brain-computer interfaces.
CDC50 orthologues in Plasmodium falciparum have distinct roles in merozoite egress and trophozoite maturation
Authors: Patel Avnish , Nofal Stephanie D. , Blackman Michael J. , Baker David A. 
Published: January 2022

AbstractIn model organisms P4-ATPases require cell division control protein 50 (CDC50) chaperones for their phospholipid flipping activity. In the malaria parasite, P. falciparum, guanylyl cyclase alpha (GCα) is an integral membrane protein that is essential for release (egress) of merozoites from their host erythrocytes. GCα is unusual in that it contains both a C-terminal cyclase domain and an N-terminal P4-ATPase domain of unknown function. We sought to investigate whether any of the three CDC50 orthologues (denoted A, B and C) encoded by P. falciparum are required for GCα function. Using gene tagging and conditional gene disruption, we demonstrate that both CDC50B and CDC50C are expressed in the clinically important asexual blood stages and that CDC50B is a binding partner of GCα whereas CDC50C is the binding partner of another putative P4-ATPase, ATP2. Our findings indicate that CDC50B has no essential role for intraerythrocytic parasite maturation but modulates the rate of parasite egress by interacting with GCα for optimal cGMP synthesis. In contrast, CDC50C is essential for blood stage trophozoite maturation. Additionally, we find that the CDC50C-ATP2 complex may influence parasite endocytosis of host cell haemoglobin and consequently hemozoin formation.
Ubiquitinome analysis of articular cartilage post mechanical injury reveals a differential ubiquitination pattern of a subset of DUBs and proteins linked to the ERAD cellular response
Authors: Kaokhum Nitchakarn , Pinto-Fernández Adán , Wilkinson Mark , Kessler Benedikt , Ismail Heba 
Published: January 2022

AbstractUnderstanding how connective tissue cells respond to mechanical stimulation is important to human health and disease processes in musculoskeletal diseases. Injury to articular cartilage is a key risk factor in predisposition to osteoarthritis. Here we identified a ubiquitin signature that is unique to injured articular cartilage tissue (the “injury ubiquitinome”). A total of 408 ubiquitinated peptides mapped to 114 proteins were identified, with an enrichment of ubiquitinated peptides of proteins involved in protein processing in the endoplasmic reticulum(ER), also known as the ER-associated degradation(ERAD) response, including YOD1, BRCC3, ATXN3 and USP5 as well as the ER stress regulators, RAD23B, VCP/p97 and Ubiquilin 1. Enrichment of these proteins suggested an injury-induced ER stress response and, for instance, ER stress markers DDIT3/CHOP and BIP/GRP78 were upregulated following cartilage injury on the protein and gene expression levels. Similar ER stress induction was also observed in response to tail fin injury in zebrafish larvae, suggesting a generic response to tissue injury. Furthermore, a rapid increase in global DUB activity following injury and significant activity in human osteoarthritic cartilage was observed using DUB specific activity probes. Inhibition of DUBs using a broad-spectrum inhibitor caused a reduction in the injury-induced inflammatory response in a zebrafish tail fin injury model. These results implicate the involvement of ubiquitination events and activation of a set of DUBs and ER stress regulators in cellular responses to cartilage tissue injury and osteoarthritis. This link through the ERAD pathway makes this protein set attractive for further investigation inin vivomodels of tissue injury and for targeting in osteoarthritis and related musculoskeletal diseases.
On the illusion of auxotrophy:met15Δyeast cells can grow on inorganic sulfur thanks to the previously uncharacterized homocysteine synthase Yll058w
Authors: Van Oss S. Branden , Parikh Saurin Bipin , Coelho Nelson Castilho , Wacholder Aaron , Belashov Ivan , Zdancewicz Sara , Michaca Manuel , Xu Jiazhen , Kang Yun Pyo , Ward Nathan P. , Yoon Sang Jun , McCourt Katherine M. , McKee Jake , Ideker Trey , VanDemark Andrew P. , DeNicola Gina M. , Carvunis Anne-Ruxandra 
Published: January 2022

ABSTRACTOrganisms must either synthesize or assimilate essential organic compounds to survive. The homocysteine synthase Met15 has been considered essential for inorganic sulfur assimilation in yeast since its discovery in the 1970s. As a result,MET15has served as a genetic marker for hundreds of experiments that play a foundational role in eukaryote genetics and systems biology. Nevertheless, we demonstrate here through structural and evolutionary modeling,in vitrokinetic assays, and genetic complementation, that an alternative homocysteine synthase encoded by the previously uncharacterized gene YLL058W enables cells lacking Met15 to assimilate enough inorganic sulfur for survival and proliferation. These cells however fail to grow in patches or liquid cultures unless provided with exogenous methionine or other organosulfurs. We show that this growth failure, which has historically justified the status ofMET15as a classic auxotrophic marker, is largely explained by toxic accumulation of the gas hydrogen sulfide due to a metabolic bottleneck. When patched or cultured with a hydrogen sulfide chelator, and when propagated as colony grids, cells without Met15 assimilate inorganic sulfur and grow, and cells with Met15 achieve even higher yields. Thus, Met15 is not essential for inorganic sulfur assimilation in yeast. Instead,MET15is the first example of a yeast gene whose loss conditionally prevents growth in a manner that depends on local gas exchange. Our results have broad implications for investigations of sulfur metabolism, including studies of stress response, methionine restriction, and aging. More generally, our findings illustrate how unappreciated experimental variables can obfuscate biological discovery.
Ex Vivo Validation of Six FDA-Approved Non-Receptor Tyrosine Kinase Inhibitors (NRTKIs) as Antivirals to Pandemic and Seasonal Influenza A Viruses
Authors: Meineke Robert , Stelz Sonja , Busch Maximilian , Werlein Christopher , Kühnel Mark , Jonigk Danny , Rimmelzwaan Guus F. , Elbahesh Husni 
Published: January 2022

ABSTRACTInfluenza viruses are important respiratory pathogens that cause substantial morbidity and mortality annually. In addition to seasonal influenza outbreaks, new emerging influenza A viruses (IAV) can cause pandemic influenza outbreaks. Apart from effective vaccines, there is a need for better treatment options to combat infections with these viruses when vaccines are not available or show reduced efficacy (e.g., in immmunocompromised patients). The limited range of licensed antiviral drugs and emergence of drug-resistance mutations highlight the need for novel intervention strategies like host-targeted antivirals. Repurposing FDA-approved kinase inhibitors may offer a fast-track for a new generation of host-targeted antivirals. Small molecule kinase inhibitors (SMKIs) can inhibit replication of viruses and improve survival in vivo; however, no SMKI has been approved for clinical use against IAV infections. In the present study, we tested eight non-receptor tyrosine kinase-inhibitors (NRTKIs) used to treat cancer and autoimmune diseases for their antiviral potential. Six of those potently inhibited virus replication (≥1,000-fold) in A549 cells infected with either A(H1N1)pdm09 or seasonal A(H3N2) strains. These compounds were validated in a biologically relevant ex vivo model of human precision-cut lung slices (hPCLS) to provide proof of principle and show efficacy against contemporary seasonal and pandemic IAVs. We identified the steps of the virus infection cycle affected by these inhibitors and assessed the effect of these NRTKIs on the host response. Considering their established safety profiles, our studies show that the use of these NRTKI shows promise and warrants further development as an alternative strategy to treat influenza virus infections.
Electric field simulations of field grading techniques in HVDC cable joints
Authors: Jörgens Christoph , Clemens Markus 
Published: January 2022

Purpose
In high voltage direct current cable systems, cable joints are known as the least reliable components due to the use of multiple dielectrics. Resulting from the electric field and temperature depending conductivity of the different dielectrics, field enhancement at critical areas, e.g. triple points, may result in accelerated aging and the failure of the component. To reduce the stress, different field grading techniques are applied. The purpose of this study is to investigate different grading techniques for cable joints. Different shapes of the electrode and a varying nonlinear conductivity of field grading materials (FGM) are used for the simulation of the electric field.

Design/methodology/approach
Coupled electro-thermal field simulations are applied for different joint geometries, to obtain the stationary electric field. Electric field simulations in cable joint using geometric and nonlinear field grading techniques are shown.

Findings
Using the geometric field grading, the shape of the stress cone determines the field values in critical areas (triple points). High stress reduction is obtained for a certain curvature of the stress cone. For the nonlinear stress control, materials with a higher conductivity in comparison to the cable and the joint material are used. A field reduction is obtained by increasing the total conductivity. On the other hand, this is also increasing the insulation losses within the total FGM. More applicable is the decrease of the switching field or the increase of nonlinearity, which is only locally increase the conductivity and the insulation losses. Furthermore, simulations results show that an approximately constant field reduction is obtained, if the nonlinearity is above a certain threshold.

Research limitations/implications
This study is restricted to a field dependency of FGM only. For impulse voltages, high temperature and electric conductivity values my result in a thermal runaway. Furthermore, only direct current field grading techniques are studied.

Originality/value
The field grading of cable joints, using geometric and nonlinear techniques, is analyzed. A comparison between the electric field, by varying the curvature of the ground stress cone or the FGM conductivity constants in a complex joint geometry is novel. With its effect on the electric fields, general requirements for the geometry (geometric field grading) or the values of the FGM constants (nonlinear field grading) are defined to obtain a sufficient field grading.
Impact of nutrition service attributes on patient satisfaction: evidence from an outpatient clinic at a Lebanese-Middle Eastern hospital
Authors: Serhan Mireille , Toutounji Batoul , Serhan Carole 
Published: January 2022

PurposeThe purpose of this paper is to explore the existing literature on the relationship between different service attributes and patient satisfaction at outpatient nutrition clinics to propose and test a culture-specific conceptual model interlinking the drivers of patient satisfaction.Design/methodology/approachOver a 7-week period in Fall 2019 (November 2–December 19), 600 patients from a Lebanese-Middle Eastern hospital (396 females and 204 males) completed an anonymous-designed survey with closed questions (n = 30). Statements were considered to represent specific attributes of nutrition services. In order to measure the existence and degree of significant relationships between different research variables, Pearson correlation coefficients and Fisher'sZtest were employed to analyze the collected data, before and while joining the clinic, during and after the appointment. Means of scores and frequencies were calculated.FindingsThe results show that the nutrition service attributes with reference to “after the appointment” may improve the patients' satisfaction level more than attributes with reference to “while joining the clinic” and “during the appointment”. Most patients were satisfied with their overall outpatient clinic experience. The patient experience is a direct result of positive interactions with the entire services offered.Practical implicationsThe conceptual model sets the foundations for testing and for further research to develop. Moreover, the findings of this study are important for assessing the quality of nutrition service attributes and for reporting on the ability of this service to meet the needs and preferences of patients in the health care sector.Originality/valueThis study attempts to fill the gap in knowledge on nutrition service quality as indicators for overall patient satisfaction, while opening clear research avenues for further studies to follow. It is the basis for the development of clinical practice guidelines and other quality enhancement tools.
Multiple butterfly recognition based on deep residual learning and image analysis
Authors: Xi Tianyu , Wang Jiangning , Han Yan , Lin Congtian , Ji Liqiang 
Published: January 2022

AbstractInsect recognition is crucial for taxonomy. It helps researchers to process tremendous and various ecology data. Most studies focus on fine‐tuning the deep learning network or altering the algorithm to enhance the identification accuracy, and some useful tools have been generated with these methods. This study focuses on the influence of image data on the recognition model. The single data set source of the existing automated identification tools is relatively simple, and the competition‐based data set released only focuses on evaluating the model at present. For the first time, this article integrates butterfly image data sets from multiple sources, covered illustrated books, and popular butterfly science websites. The image types include standard specimen images, illustrated book scan images and camera shots. In addition, these images included not only fixed poses, but also various other images of butterflies in natural poses. The size of these images is also various. The testing data set is new data that does not belong to the training set, which also verifies the generalizability of the model, indicating that in practical applications this model can identify new images. This testing method is a breakthrough compared to the previous work. We designed different data sets using the ResNet18 network to train a classifier, which achieves a validation accuracy of 86% in the end of the analysis. By adjusting the data sets, the accuracy changes as well. This study provides a method to recognize hundreds of butterfly species and analyzes the testing progress from the point of view of data. It is the first to combine butterflies from multiple countries in a single data set, with a recognition accuracy that outperforms previous experiments, to the best of our knowledge. We further analyze the testing results of butterfly recognition at the family and genus level. We perform two more experiments to demonstrate the model in the case of similar species or genus.