bluuebunny/crossref_metadata_2025_split huggingface dataset:
A signature of pre-operative biomarkers of cellular senescence to predict risk of cardiac and kidney adverse events after cardiac surgery
Authors: Entwistle Amy , Walker Susan , Knecht Anne , Strum Susan L. , Shah Asad , Podgoreanu Mihai V. , Pustavoitau Aliaksei , Mitin Natalia , Williams Judson B. 
Published: April 2023

ABSTRACTObjectiveUnderstand the potential for pre-operative biomarkers of cellular senescence, a primary aging mechanism, to predict risk of cardiac surgery-associated adverse events.MethodsBiomarkers of senescence were assessed in blood samples collected prior to surgery in 331 patients undergoing CABG +/-valve repair or replacement. Patients were followed throughout the hospital stay and at a 30-day follow-up visit. Logistic regression models for pre-operative risk prediction were built for age-related clinical outcomes with high incidence including KDIGO-defined acute kidney injury (AKI), decline in eGFR ≥25% between pre-op and 30 days, and MACKE30, a composite endpoint of major adverse cardiac and kidney events at 30d.ResultsAKI occurred in 19.9% of patients, persistent decline in kidney function at 30d occurred in 11.0%, and MACKE30 occurred in 13.4%. A network of six biomarkers of senescence (p16, p14, LAG3, CD244, CD28 and suPAR) were able to identify patients at risk for AKI (AUC 0.76), kidney decline at 30d (AUC 0.73), and MACKE30 (AUC 0.71). Comparing the top and bottom tertiles of senescence-based risk models, patients in the top tertile had 7.8 (3.3-8.4) higher odds of developing AKI, 4.5 (1.6-12.6) higher odds of developing renal decline at 30d, and 5.7 (2.1-15.6) higher odds of developing MACKE30. All models remained significant when adjusted for clinical variables. Patients with kidney function decline at 30d were largely non-overlapping and clinically distinct from those who experienced AKI, suggesting a different etiology. Typical clinical factors that predispose to AKI (e.g., age, CKD, surgery type) associated with AKI but not the 30d decline endpoint which was instead associated with new-onset atrial fibrillation.ConclusionsA six-member network of biomarkers of senescence, a fundamental mechanism of aging, can identify patients for risk of adverse kidney and cardiac events when measured pre-operatively.
Sensitive quantification of cerebellar speech abnormalities using deep learning models
Authors: Vattis Kyriakos , Luddy Anna C. , Ouillon Jessey S. , Eklund Nicole M. , Stephen Christopher D. , Schmahmann Jeremy D. , Nunes Adonay S. , Gupta Anoopum S. 
Published: April 2023

AbstractObjectiveObjective, sensitive, and meaningful disease assessments are critical to support clinical trials and clinical care. Speech changes are one of the earliest and most evident manifestations of cerebellar ataxias. The purpose of this work is to develop models that can accurately identify and quantify these abnormalities.MethodsWe use deep learning models such asResNet 18, that take the time and frequency partial derivatives of the log-mel spectrogram representations of speech as input, to learn representations that capture the motor speech phenotype of cerebellar ataxia. We train classification models to separate patients with ataxia from healthy controls as well as regression models to estimate disease severity.ResultsOur model was able to accurately distinguish healthy controls from individuals with ataxia, including ataxia participants with no detectable clinical deficits in speech. Furthermore the regression models produced accurate estimates of disease severity, were able to measure subclinical signs of ataxia, and captured disease progression over time in individuals with ataxia.ConclusionDeep learning models, trained on time and frequency partial derivatives of the speech signal, can detect sub-clinical speech changes in ataxias and sensitively measure disease change over time.SignificanceSuch models have the potential to assist with early detection of ataxia and to provide sensitive and low-burden assessment tools in support of clinical trials and neurological care.
The epidemiological characteristics of stroke phenotypes defined with ICD-10 and free-text: a cohort study linked to electronic health records
Authors: Davidson Emma M , Casey Arlene , Grover Claire , Alex Beatrice , Wu Honghan , Campbell Archie , Chalmers Fionna , Adams Mark , Iveson Matthew , McIntosh Andrew M , Ball Emily , Rannikmae Kristiina , Whalley Heather , Whiteley William N 
Published: April 2023

AbstractBackgroundCoded healthcare data may not capture all stroke cases and has limited accuracy for stroke subtypes. We sought to determine the incremental value of adding natural language processing (NLP) of free-text radiology reports to international classification of disease (ICD-10) codes to phenotype stroke, and stroke subtypes, in routinely collected healthcare datasets.MethodsWe linked participants in a community-based prospective cohort study, Generation Scotland, to clinical brain imaging reports (2008-2020) from five Scottish health boards. We used five combinations of NLP outputs and ICD-10 codes to define stroke phenotypes. With these phenotype models we measured the: stroke incidence standardised to a European Standardised Population; adjusted hazard ratio (aHR) of baseline hypertension for later stroke; and proportion of participants allocated stroke subtypes.ResultsOf 19,026 participants, over a mean follow-up of 10.2 years, 1938 had 3493 brain scans. Any stroke was identified in 534 participants: 319 with NLP alone, 59 with ICD-10 codes alone and 156 with both ICD-10 codes and an NLP report consistent with stroke. The stroke aHR for baseline hypertension was 1.47 (95%CI: 1.12-1.92) for NLP-defined stroke only; 1.57 (95%CI: 1.18-2.10) for ICD-10 defined stroke only; and 1.81 (95%CI: 1.20-2.72) for cases with ICD 10 stroke codes and NLP stroke phenotypes. The age-standardised incidence of stroke for these phenotype models was 1.35, 1.34, and 0.65 per 1000 person years, respectively. The proportion of strokes not subtyped was 26% (57/215) using only ICD-10, 9% (42/467) using only NLP, and 12% (65/534) using both NLP and ICD-10.ConclusionsAddition of NLP derived phenotypes to ICD-10 stroke codes identified approximately 2.5 times more stroke cases and greatly increased the proportion with subtyping. The phenotype model using ICD 10 stroke codes and NLP stroke phenotypes had the strongest association with baseline hypertension. This information is relevant to large cohort studies and clinical trials that use routine electronic health records for outcome ascertainment.
The characterisation of antimicrobial resistantEscherichia colifrom dairy calves
Authors: Mwenifumbo Merning , Cookson Adrian L , Zhao Shengguo , Fayaz Ahmed , Benschop Jackie , Burgess Sara A 
Published: April 2023

ABSTRACTDairy calves, particularly pre-weaned calves have been identified as a common source of multidrug (MDR) resistantE. coli. However, the strains and whether their resistance genes are plasmid or chromosomally located have not been well characterised. Our study examined the phenotype and genotype of antimicrobial resistantE. coliisolated from young calves (≤ 14 days old). Recto-anal swab enrichments from 40 dairy calves located on four dairy farms were examined for tetracycline, streptomycin, ciprofloxacin, and third-generation cephalosporin resistantE. coli. Fifty-eight percent (23/40) of calves harboured antimicrobial resistantE. coli: 18/40 (45%) harboured tetracycline resistant and 25% (10/40) harboured chromosomal mediated AmpC producingE. coli. Whole genome sequencing of 27 isolates revealed five sequence types, with ST88 being the dominant ST (17/27, 63% of the sequenced isolates) followed by ST1308 (3/27, 11%), along with the extraintestinal pathogenicE. colilineages ST69 (3/27), ST10 (2/27, 7%), and ST58 (1/27, 4%). Additionally, 16 isolates were MDR, harbouring additional resistance genes that were not tested phenotypically. Oxford Nanopore long-read sequencing technologies enabled the location of multiple resistant gene cassettes in IncF plasmids to be determined. A phylogenetic comparison of the ST10 and ST69 isolates demonstrated that the calf derived isolates were distinct from other New Zealand animal, human, and environmental isolates. and highlights the importance of understanding the sources of antimicrobial resistance.
Identifying determinants of synaptic specificity by integrating connectomes and transcriptomes
Authors: Yoo Juyoun , Dombrovski Mark , Mirshahidi Parmis , Nern Aljoscha , LoCascio Samuel A. , Zipursky S. Lawrence , Kurmangaliyev Yerbol Z. 
Published: April 2023

SummaryHow do developing neurons select their synaptic partners? To identify molecules matching synaptic partners, we integrated the synapse-level connectome of neural circuits with the developmental expression patterns and binding specificities of cell adhesion molecules (CAMs) on pre- and postsynaptic neurons. We focused on parallel synaptic pathways in the Drosophila visual system, in which closely related neurons form synapses onto closely related target neurons. We show that the choice of synaptic partners correlates with the matching expression of receptor-ligand pairs of Beat and Side proteins of the immunoglobulin superfamily (IgSF) CAMs. Genetic analysis demonstrates that these proteins determine the choice between alternative synaptic targets. Combining transcriptomes, connectomes, and protein interactome maps provides a framework to uncover the molecular logic of synaptic connectivity.
The genomic architecture of a continuous color polymorphism in the European barn owl (Tyto alba)
Authors: Cumer Tristan , Machado Ana Paula , San-Jose Luis M. , Ducrest Anne-Lyse , Simon Céline , Roulin Alexandre , Goudet Jérôme 
Published: April 2023

AbstractThe maintenance of color polymorphism in populations has fascinated evolutionary biologists for decades. Studies of color variation in wild populations often focus on discrete color traits exhibiting simple inheritance patterns, while studies on continuously varying traits remain rare. Here, we studied the continuous white to rufous color polymorphism in the European barn owl (Tyto alba). Using a Genome Wide Association approach on whole-genome data of 75 barn owls sampled across Europe, we identified, in addition to a previously knownMC1Rmutation, two regions involved in this color polymorphism. We show that the combination of the three explains 80.37% (95% credible interval 58.45 to 100%) of the color variation. Among the two newly identified regions, the one on the sexual chromosome (Z) shows a large signal of differentiation in the Swiss population when contrasting individuals with different morph but the sameMC1Rgenotype. We suggest it may play a role in the sexual dimorphism observed locally in the species. These results, uncovering two new genomic regions, provide keys to better understand the molecular bases of the color polymorphism as well as the mechanisms responsible for its maintenance in the European barn owl at both continental and local scales.
High-throughput colocalization pipeline quantifies efficacy of mitochondrial targeting signals across different protein types
Authors: Lear Sierra K. , Nunez Jose A. , Shipman Seth L. 
Published: April 2023

ABSTRACTEfficient metabolic engineering and the development of mitochondrial therapeutics often rely upon the specific and strong import of foreign proteins into mitochondria. Fusing a protein to a mitochondria-bound signal peptide is a common method to localize proteins to mitochondria, but this strategy is not universally effective with particular proteins empirically failing to localize. To help overcome this barrier, this work develops a generalizable and open-source framework to design proteins for mitochondrial import and quantify their specific localization. By using a Python-based pipeline to quantitatively assess the colocalization of different proteins previously used for precise genome editing in a high-throughput manner, we reveal signal peptide-protein combinations that localize well in mitochondria and, more broadly, general trends about the overall reliability of commonly used mitochondrial targeting signals.
Gut bacteria translocation to the brain after ischaemic stroke occurs via the sympathetic nervous system
Authors: Peh Alex , Dinakis Evany , Nakai Michael , Muralitharan Rikeish R. , Rupasinghe Samoda , Wilson Jenny L. , Wong Connie H.Y. , Jama Hamdi , Barker Charlotte M.O. , Modarresi Mahnaz , Kemp-Harper Barbara K. , Zheng Tenghao , Marques Francine Z. , Broughton Brad R.S. 
Published: April 2023

AbstractWe provide evidence that stroke-induced gut breakdown results in bacteria translocation to the ischaemic mouse brain. Inhibition of sympathetic tone reduced bacterial load in the post-stroke brain and reduced functional deficits without altering cerebral apoptosis, neuroinflammation or infarct volume. These findings indicate that the activation of the sympathetic nervous system after stroke promotes gut-derived bacteria to enter to the brain, and this process worsens motor function in mice.Abstract Figure
Analytical solutions for the short-term plasticity
Authors: Protachevicz Paulo R. , Batista Antonio M. , Caldas Iberê L. , Baptista Murilo S. 
Published: April 2023

AbstractSynaptic dynamics plays a key role in neuronal communication. Due to its high-dimensionality, the main fundamental mechanisms triggering different synaptic dynamics and its relation with the neurotransmitters release regimes (facilitation, biphasic, and depression) are still elusive. For a general set of parameters, and by means of an approximated solution for a set of differential equations associated with a synaptic model, we obtain a discrete map that provides analytical solutions that shed light into the dynamics of synapses. Assuming that the presynaptic neuron perturbing the neuron whose synapse is being modelled is spiking periodically, we derive the stable equilibria and the maximal values for the release regimes as a function of the percentage of neurotransmitter released and the mean frequency of the presynaptic spiking neuron. Assuming that the presynaptic neuron is spiking stochastically following a Poisson distribution, we demonstrate that the equations for the time average of the trajectory are the same as the map under the periodic presynaptic stimulus, admitting the same equilibrium points. Thus, the synapses under stochastic presynaptic spikes, emulating the spiking behaviour produced by a complex neural network, wander around the equilibrium points of the synapses under periodic stimulus, which can be fully analytically calculated.Author summaryBased on the model proposed by Tsodyks et al., we obtained a map approximation to study analytically the dynamics of short-term synaptic plasticity. We identified the synaptic regimes named facilitation, depression, and biphasic in the parameters space, and determined the maximal and equilibrium points of active neurotransmitters for presynaptic neurons spiking periodically and stochastically following a Poisson process. Besides that, we verify that the time average of the variables for the synaptic dynamics driven by presynaptic neurons spiking following a Poisson distribution presents the equilibrium points obtained for the synaptic driven by periodic presynaptic neurons, spiking with a frequency that is the mean frequency of the Poisson distribution. These results shed analytical light into the understanding of synaptic dynamics.
Ribosomal protein RPL39L is an efficiency factor in the cotranslational folding of proteins with alpha helical domains
Authors: Banerjee Arka , Ataman Meric , Smialek Maciej Jerzy , Mookherjee Debdatto , Rabl Julius , Mironov Aleksei , Mues Lea , Enkler Ludovic , Coto-Llerena Mairene , Schmidt Alexander , Boehringer Daniel , Piscuoglio Salvatore , Spang Anne , Mittal Nitish , Zavolan Mihaela 
Published: April 2023

AbstractIncreasingly many studies reveal how ribosome composition can be tuned to optimally translate the transcriptome of individual cell types. In this study, we investigated the expression pattern, structure within the ribosome and effect on protein synthesis of the ribosomal protein paralog 39L (RPL39L). With a novel mass spectrometric approach we have quantified the expression of RPL39L in human pluripotent cells, cancer cell lines and tissue samples, and in mouse germ cells. We generatedRPL39Lknock-out mouse embryonic stem cell (mESC) lines and demonstrated that RPL39L impacts the dynamics of translation, to support the pluripotency and differentiation, spontaneous and along the germ cell lineage. Most differences in protein abundance between WT and RPL39L KO lines were explained by widespread proteasomal activity. By CryoEM analysis of purified RPL39 and RPL39L-containing ribosomes we found that, unlike RPL39, RPL39L has two distinct conformations in the exposed segment of the nascent peptide exit tunnel, creating a distinct hydrophobic patch that has been predicted to support the efficient co-translational folding of alpha helices. Our study shows that ribosomal protein paralogs provide switchable modular components that can tune translation to the protein production needs of individual cell types.
Modification of amyloplast size in wheat endosperm through mutation of PARC6 affects starch granule morphology
Authors: Esch Lara , Ngai Qi Yang , Barclay J. Elaine , McNelly Rose , Hayta Sadiye , Smedley Mark A. , Smith Alison M. , Seung David 
Published: April 2023

AbstractStarch granule morphology is a major factor determining the functional and nutritional properties of starch. Here, we reveal amyloplast structure plays an important role in starch granule morphogenesis in wheat endosperm. Wheat amyloplasts contain large discoid A-type granules and small spherical B-type granules. We isolated a mutant in durum wheat defective in the plastid division protein PARC6, which had increased plastid size in both leaves and endosperm. Endosperm amyloplasts of the mutant contained more A- and B-type granules than those of the wild type. In mature grains, the mutant had larger A- and B-type granules than the wild type, and its A-type granules had a highly aberrant, lobed surface. This defect in granule morphology was already evident at early stages of grain development, when granule size was identical between the mutant and the wild type, and occurred without obvious alterations in starch polymer structure and composition. Plant growth and photosynthetic efficiency, as well as the size, number and starch content of grains, were not affected in theTtparc6mutants despite the large changes in plastid size. Interestingly, mutation of the PARC6 paralog, ARC6, in durum wheat did not increase plastid or starch granule size. We suggest this is becauseTtPARC6 can complement disruptedTtARC6 function by interacting with PDV2, the outer plastid envelope protein that typically interacts with ARC6 to promote plastid division. We propose that amyloplast compartment size and available stromal volume play important roles in determining starch granule size, shape and number per amyloplast.
Comparative analysis of the effects of retinoic acid versus paclitaxel and everolimus on HL60 cells proliferation and viability
Authors: Zampouka Athanasia , Papadimitropoulou Triantafyllia , Salagianni Maria , Vaiou Maria , Moula Amalia I , Giannoukas Athanasios , Moulas Anargyros N 
Published: April 2023

AbstractPurposeAll trans-retinoic acid (atRA) has been proposed as a novel drug for drug eluting stents (DES). Currently complications of DES have been at least partially attributed to the drugs that are used: paclitaxel and sirolimus and its derivatives like everolimus. We compared the effects of atRA, paclitaxel and everolimus on the proliferation and viability of human leukemia cells (HL60).MethodsCells were cultured with 0.1μM and 10μM of atRA, paclitaxel or everolimus. Cell proliferation and viability was evaluated with trypan blue at 24, 48 and 72 hours.ResultsAll drugs caused a statistically significant, dose-dependent reduction of cell proliferation rate from the first 24 hours. atRA and everolimus did not affect cell viability as the treated cells showed high viability (95-98%), while paclitaxel decreased significantly the viability to below 16% at 72 hours. Unlike the cytotoxic effect of paclitaxel on HL60, atRA demonstrated a cytostatic effect comparable to everolimus.ConclusionThe ability of atRA to limit cell proliferation without affecting cell viability in a manner similar to everolimus, highlights its potential to be used on DES as a novel drug for treatment of restenosis with potentially minimal side-effects. Further research with different cell types, is needed in order to elucidate the possible usefulness of RA on DES.
The DEAD-box helicase RCF1 plays roles in miRNA biogenesis and RNA splicing inArabidopsis
Authors: Xu Chi , Zhang Zhanhui , He Juan , Bai Yongsheng , Liu Lin , Tang Jihua , Tang Guiliang , Chen Xuemei , Mo Beixin 
Published: April 2023

AbstractRCF1 is a highly conserved DEAD-box helicase found in yeast, plants and mammals. Studies about the functions of RCF1 in plants are limited. Here we uncovered the functions of RCF1 inArabidopsis thalianaas a player in pri-miRNA processing and splicing, as well as in pre-mRNA splicing. A mutant with miRNA biogenesis defects was isolated and the defect was traced to a recessive point mutation inRCF1(rcf1-4). We show that RCF1 promotes D-body formation and facilitates the interaction between pri-miRNAs and HYL1. Finally, we show that intron-containing pri-miRNAs and pre-mRNAs exhibit a global splicing defect inrcf1-4. Together, this work uncovers roles for RCF1 in miRNA biogenesis and RNA splicing inArabidopsis.One-sentence summaryRCF1 promotes not only the processing of pri-miRNAs, but also the splicing of intron-containing pri-miRNAs, therefore promotes miRNA biogenesis.
Transsynaptic labeling and transcriptional control of zebrafish neural circuits
Authors: Coomer Cagney , Naumova Daria , Talay Mustafa , Zolyomi Bence , Snell Nathaniel J. , Sorkaç Altar , Chanchu Jean-Michale , Cheng Ji , Roman Ivana , Li Jennifer , Robson Drew , Barnea Gilad , Halpern Marnie E. 
Published: April 2023

AbstractDeciphering the connectome, the ensemble of synaptic connections that underlie brain function, is a central goal of neuroscience research. Here, we report mapping of connections between presynaptic and postsynaptic partners in a living vertebrate nervous system, that of the zebrafish, through the successful adaptation of thetrans-Tango genetic approach, first developed for anterograde transsynaptic tracing inDrosophila. Neural connections were visualized between synaptic partners in the larval retina and brain and followed over development. Results were corroborated by functional experiments in which optogenetic activation of retinal ganglion cells elicited responses in neurons of the optic tectum, as measured bytrans-Tango-dependent expression of a genetically encoded calcium indicator.Transsynaptic signaling throughtrans-Tango reveals predicted as well as previously undescribed synaptic connections in the zebrafish brain, providing a valuablein vivotool to monitor and interrogate neural circuits over time.