bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted rescue of synaptic plasticity improves cognitive decline after severe systemic inflammation
Authors: Grünewald Benedikt , Wickel Jonathan , Hahn Nina , Hörhold Franziska , Rupp Hanna , Chung Ha-Yeun , Haselmann Holger , Strauss Anja S. , Schmidl Lars , Hempel Nina , Grünewald Lena , Urbach Anja , Bauer Michael , Toyka Klaus V. , Blaess Markus , Claus Ralf A. , König Rainer , Geis Christian 
Published: March 2021

AbstractSepsis-associated encephalopathy (SAE) is a frequent complication in patients with severe systemic infection resulting in acute brain dysfunction and incapacitating long-term sequelae. SAE includes delirium, premature death, post-traumatic stress disorder, and major long-term cognitive impairment. The underlying pathophysiology of SAE is largely unresolved and specific treatment options are missing. We induced the peritoneal contamination and infection (PCI) sepsis model in 769 mice and compared these with 259 control mice. We found that experimental sepsis causes synaptic pathology in the brain characterized by severely disordered synaptic plasticity with reduced long-term potentiation, changes in CA1 pyramidal neuron dendritic spines, and behavioral abnormalities indicating cognitive dysfunction. Using electrophysiology, we found reduced frequency of quantal and spontaneous excitatory postsynaptic currents whereas amplitudes of miniature, spontaneous, and evoked excitatory currents were increased, pointing towards a homeostatic synaptic scaling mechanism. Corresponding to dysfunctional excitatory synaptic function we discovered downregulation of genes related to neuronal and synaptic signaling in the brain, including the gene for activity-regulated cytoskeleton-associated protein (Arc/Arg3.1), members of the transcription-regulatory EGR gene family, and the gene for dual-specificity phosphatase 6 (Dusp6). At the protein level, ARC expression and MAP kinase signaling in the brain were affected. For targeted rescue of dysfunctional synaptic signaling and plasticity, we overexpressed ARC in the hippocampus by microinjection of an adeno-associated virus containing a neuron-specific plasmid of the ARC transgene. Hereby we achieved recovery of defective synaptic plasticity in the hippocampal Schaffer collateral-CA1 pathway and improvement of memory dysfunction. Using a different rescue paradigm, PCI mice were subjected to enriched environment providing multiple activating stimuli. Enriched environment led to restoration of disordered long-term potentiation and memory, thus demonstrating the potential for activity-induced improvement. Together, we identified synaptic pathomechanisms of SAE after severe systemic infection and provide a conceptual approach to treat SAE-related disease mechanisms which may be applicable to patients afflicted with SAE.
sRNARFTarget: A fast machine-learning-based approach for transcriptome-wide sRNA Target Prediction
Authors: Naskulwar Kratika , Peña-Castillo Lourdes 
Published: March 2021

AbstractBacterial small regulatory RNAs (sRNAs) are key regulators of gene expression in many processes related to adaptive responses. A multitude of sRNAs have been identified in many bacterial species; however, their function has yet to be elucidated. A key step to understand sRNAs function is to identify the mRNAs these sRNAs bind to. There are several computational methods for sRNA target prediction, and the most accurate one is CopraRNA which is based on comparative-genomics. However, species-specific sRNAs are quite common and CopraRNA cannot be used for these sRNAs. The most commonly used transcriptome-wide sRNA target prediction method and second-most-accurate method is IntaRNA. However, IntaRNA can take hours to run on a bacterial transcriptome. Here we present sRNARFTarget, a machine-learning-based method for transcriptome-wide sRNA target prediction applicable to any sRNA. We comparatively assessed the performance of sRNARFTarget, CopraRNA and IntaRNA in three bacterial species. Our results show that sRNARFTarget outperforms IntaRNA in terms of accuracy, ranking of true interacting pairs, and running time. However, CopraRNA substantially outperforms the other two programs in terms of accuracy. Thus, we suggest using CopraRNA when homolog sequences of the sRNA are available, and sRNARFTarget for transcriptome-wide prediction or for species-specific sRNAs. sRNARFTarget is available athttps://github.com/BioinformaticsLabAtMUN/sRNARFTarget.
Deep learning-based quantification of arbuscular mycorrhizal fungi in plant roots
Authors: Evangelisti Edouard , Turner Carl , McDowell Alice , Shenhav Liron , Yunusov Temur , Gavrin Aleksandr , Servante Emily K. , Quan Clément , Schornack Sebastian 
Published: March 2021

SummarySoil fungi establish mutualistic interactions with the roots of most vascular land plants. Arbuscular mycorrhizal (AM) fungi are among the most extensively characterised mycobionts to date. Current approaches to quantifying the extent of root colonisation and the abundance of hyphal structures in mutant roots rely on staining and human scoring involving simple, yet repetitive tasks prone to variations between experimenters.We developed AMFinder which allows for automatic computer vision-based identification and quantification of AM fungal colonisation and intraradical hyphal structures on ink-stained root images using convolutional neural networks.AMFinder delivered high-confidence predictions on image datasets of roots of multiple plant hosts (Nicotiana benthamiana,Medicago truncatula,Lotus japonicus,Oryza sativa) and captured the altered colonisation inram1-1,strandsmax1mutants. A streamlined protocol for sample preparation and imaging allowed us to quantify mycobionts from the generaRhizophagus,Claroideoglomus,RhizoglomusandFunneliformisvia flatbed scanning or digital microscopy including dynamic increases in colonisation in whole root systems over time.AMFinder adapts to a wide array of experimental conditions. It enables accurate, reproducible analyses of plant root systems and will support better documentation of AM fungal colonisation analyses. AMFinder can be accessed here:https://github.com/SchornacklabSLCU/amfinder.git
Oxaliplatin Resistance in Colorectal Cancer Enhances TRAIL Sensitivity Via Death Receptor 4 Upregulation and Lipid Raft Localization
Authors: Greenlee Joshua D. , Lopez-Cavestany Maria , Ortiz-Otero Nerymar , Liu Kevin , Subramanian Tejas , Cagir Burt , King Michael R. 
Published: March 2021

AbstractColorectal cancer (CRC) remains a leading cause of cancer death, and its mortality is associated with metastasis and chemoresistance. We demonstrate that oxaliplatin-resistant CRC cells are sensitized to TRAIL-mediated apoptosis. Oxaliplatin-resistant cells exhibited transcriptional downregulation of caspase-10, but this had minimal effects on TRAIL sensitivity following CRISPR-Cas9 deletion of caspase-10 in parental cells. Sensitization effects in oxaliplatin-resistant cells were found to be a result of increased DR4, as well as significantly enhanced DR4 palmitoylation and translocation into lipid rafts. Raft perturbation via nystatin and resveratrol significantly altered DR4/raft colocalization and TRAIL sensitivity. Blood samples from metastatic CRC patients were treated with TRAIL liposomes, and a 57% reduction of viable CTCs was observed. Increased DR4/lipid raft colocalization in CTCs was found to correspond with increased oxaliplatin resistance and increased efficacy of TRAIL liposomes. To our knowledge, this is the first study to investigate the role of lipid rafts in primary CTCs.Impact StatementOxaliplatin-resistant colorectal cancer cells exhibit unregulated death receptor 4 expression with increased receptor palmitoylation and translocation into lipid rafts, increasing their sensitivity to apoptosis via TRAIL.
Content bias in the cultural evolution of house finch song
Authors: Youngblood Mason , Lahti David 
Published: March 2021

AbstractIn this study, we used a longitudinal dataset of house finch (Haemorhous mexicanus) song recordings spanning four decades in the introduced eastern range to assess how individual-level cultural transmission mechanisms drive population-level changes in birdsong. First, we developed an agent-based model (available as a new R package calledTransmissionBias) that simulates the cultural transmission of house finch song given different parameters related to transmission biases, or biases in social learning that modify the probability of adoption of particular cultural variants. Next, we used approximate Bayesian computation and machine learning to estimate what parameter values likely generated the temporal changes in diversity in our observed data. We found evidence that strong content bias, likely targeted towards syllable complexity, plays a central role in the cultural evolution of house finch song in western Long Island. Frequency and demonstrator biases appear to be neutral or absent. Additionally, we estimated that house finch song is transmitted with extremely high fidelity. Future studies should use our simulation framework to better understand how cultural transmission and population declines influence song diversity in wild populations.
Cardiovascular risk assessment and coronary artery calcification burden in asymptomatic patients in the initial years of hemodialysis
Authors: Kusic Milicevic Jovana , Vidakovic Radosav , Markovic Rodoljub , Andjelkovic Apostolovic Marija , Korac Mihajlo , Trbojevic Stankovic Jasna , Jemcov Tamara , Neskovic Aleksandar N. , Dragovic Gordana 
Published: March 2021

AbstractThe specific tool for cardiovascular risk assessment in hemodialysis population has not yet been proposed, despite high prevalence of cardiovascular morbidity, and mortality in clinically asymptomatic patients. Coronary artery calcium score (CACS), as a reliable predictor of future cardiovascular events, might be a valuable approach. We sought to evaluate coronary artery calcification burden and its association with clinical and laboratory parameters in asymptomatic patients who recently initiated hemodialysis. The cross‐sectional study included 60 asymptomatic patients receiving chronic hemodialysis for no longer than 48 months. CACS was assessed by cardiac computed tomography. Intima‐media thickness (IMT) of both common carotid and femoral arteries were measured using ultrasonography. The mean total CACS was 160.50 (443). Patients' age correlated significantly with CACS (σ = 0.367; P = 0.004), carotid (σ = 0.375; P = 0.004) and femoral IMT (σ = 0.323; P = 0.013). Patients with CACS = 0 were significantly younger than patients with CACS >400: 52.4 ± 7.91 vs. 63.88 ± 8.37 years old, respectively (P = 0.034). In patients receiving dialysis for longer than 24 months CACS, femoral and carotid IMT were higher than in those dialyzed for less than 24 months; however, none has reached significance. There was a significant positive correlation between CACS and right (σ = 0.312; P = 0.018) and left (σ = 0.521; P < 0.001) femoral IMT, while not with carotid. CACS showed significant negative correlation with the serum iron (σ = −0.351; P = 0.007). Calcification burden varies significantly in asymptomatic patients in early years of dialysis. It correlates with patients' age and tends to increase with dialysis vintage. Femoral IMT might be useful for cardiovascular risk stratification in asymptomatic patients who recently initiated hemodialysis.
Metabolic engineering of microorganisms for the production of multifunctional non‐protein amino acids: γ‐aminobutyric acid and δ‐aminolevulinic acid
Authors: Su Anping , Yu Qijun , Luo Ying , Yang Jinshui , Wang Entao , Yuan Hongli 
Published: March 2021

SummaryGamma‐aminobutyric acid (GABA) and delta‐aminolevulinic acid (ALA), playing important roles in agriculture, medicine and other fields, are multifunctional non‐protein amino acids with similar and comparable properties and biosynthesis pathways. Recently, microbial synthesis has become an inevitable trend to produce GABA and ALA due to its green and sustainable characteristics. In addition, the development of metabolic engineering and synthetic biology has continuously accelerated and increased the GABA and ALA yield in microorganisms. Here, focusing on the current trends in metabolic engineering strategies for microbial synthesis of GABA and ALA, we analysed and compared the efficiency of various metabolic strategies in detail. Moreover, we provide the insights to meet challenges of realizing industrially competitive strains and highlight the future perspectives of GABA and ALA production.
Prognostic impact of Notch1 receptor and clinicopathological High‐Risk Predictors in lacrimal gland adenoid cystic carcinoma
Authors: Anjum Shahzan , Sen Seema , Pushker Neelam , Bajaj Mandeep Singh , Kashyap Seema , Bakhshi Sameer , Chosdol Kunzang , Meel Rachna , Sharma Mehar Chand 
Published: March 2021

AbstractPurposeAdenoid Cystic Carcinoma (ACC) is an aggressive malignant lacrimal gland tumour associated with poor prognosis. Aberrant Notch signalling has been investigated in various tumours. However, very few studies on Notch signalling in lacrimal gland ACC are reported. The aim of the present study was to evaluate the status of Notch1 receptor and activated Notch1 (NICD1) in lacrimal gland ACC and to correlate it with high‐risk clinicopathological features.MethodsA total of 23 cases of histopathologically proven lacrimal gland ACC, who underwent surgical treatment, were included in this study. Expression of Notch1 receptor and NICD1 was evaluated by immunohistochemistry on formalin fixed paraffin embedded tissues. The results obtained were correlated with clinicopathological high‐risk features and survival of the patients. Kaplan–Meier survival and multivariate analysis was performed to determine the prognostic significance.ResultsOverexpression of Notch1 receptor and NICD1 was observed in 65% and 39% of lacrimal gland ACC cases, respectively. On Kaplan–Meier survival analysis, patients with Notch1 receptor overexpression had reduced disease free survival. On univariate analysis, male gender, bone erosion, perineural invasion, solid histologic pattern, intracranial extension and advanced tumour stage were also indicators of poor prognosis. On multivariate analysis bone erosion was the most significant poor prognostic indicator.ConclusionOur study demonstrates that overexpression of Notch1 receptor plays a critical role in the biology and aggressive behaviour of lacrimal gland ACC. Bone erosion, solid histologic pattern, advanced T stage, perineural invasion and intracranial extension are other high‐risk clinicopathological predictors of lacrimal gland ACC.
Teachers’ beliefs and practices about oral corrective feedback in university EFL classes
Authors: Yüksel Doğan , Soruç Adem , McKinley Jim 
Published: March 2021

AbstractThis study examined (in)congruences between beliefs and practices of EFL university teachers on in‐class oral corrective feedback (OCF). The participants were 20 university English language teachers from a private university in Turkey. Data were collected via video‐recorded non‐participant detached observation, a task about OCF to determine the beliefs of the teachers, and a stimulated recall interview. The results showed incongruence between what the teachers said they believed and what they did. However, teachers’ beliefs and practices were similar regarding whether the errors should be corrected, when errors should be corrected, and who should correct them. Particularly notable in this study was the finding that those teachers with the greatest incongruence almost always stood by their decisions, even after they watched their unsuccessful OCF practices.
Determinants of suboptimal blood pressure control in a multi‐ethnic population: The Healthy Life in an Urban Setting (HELIUS) study
Authors: van der Linden Eva L. , Collard Didier , Beune Erik J. A. J. , Nieuwkerk Pythia T. , Galenkamp Henrike , Haafkens Joke A. , Moll van Charante Eric P. , van den Born Bert‐Jan H. , Agyemang Charles 
Published: March 2021

AbstractAmong ethnic minority groups in Europe, blood pressure (BP) control is often suboptimal. We aimed to identify determinants of suboptimal BP control in a multi‐ethnic population. We analyzed cross‐sectional data of the Healthy Life in an Urban Setting (HELIUS) study, including 3571 participants aged 18‐70 with prescribed antihypertensive medication, of various ethnic backgrounds (500 Dutch, 1052 African Surinamese, 656 South‐Asian Surinamese, 637 Ghanaian, 433 Turkish, and 293 Moroccan) living in Amsterdam, the Netherlands. 53.3% of the population had suboptimal BP control, defined as BP ≥140/90 mmHg despite prescribed antihypertensives. Using multivariate logistic regression analysis, female sex (OR 0.50, 95%CI 0.43‐0.59), being married (0.83, 0.72‐0.96), smoking (0.78, 0.65‐0.94), alcohol intake (0.80, 0.66‐0.96), obesity (1.67, 1.35‐2.06), cardiovascular disease (CVD) history (0.56, 0.46‐0.68), non‐adherence to antihypertensives (1.26, 1.00‐1.58), and family history of hypertension (1.19, 1.02‐1.38) were identified to be independently associated with suboptimal BP control in the total population. In the ethnic‐stratified analysis, factors associated with better BP control were female sex (all ethnic groups), smoking (Turks), and CVD history (Dutch, South‐Asian Surinamese, and African Surinamese), whereas factors associated with suboptimal BP control were older age (Turks), obesity (Dutch, African Surinamese, Ghanaian, and Turks), and non‐adherence to antihypertensives (Dutch). In conclusion, our analysis identifies several key determinants that are independently associated with suboptimal BP control in a multi‐ethnic population, with some important variations between ethnic groups. Targeting these determinants may help to improve BP control.
PRMT5 promotes colorectal cancer growth by interaction with MCM7
Authors: Li Xiangwei , Wang Xin , Zhao Jiahui , Wang Jian , Wu Jingjing 
Published: March 2021

AbstractProtein arginine methyltransferase 5 (PRMT5) is a type of methyltransferase enzyme that can catalyse arginine methylation of histones and non‐histone proteins. Accumulating evidence indicates that PRMT5 promotes cancer development and progression. However, its function in colorectal cancer (CRC) is poorly understood. In this study, we revealed the oncogenic roles of PRMT5 in CRC. We found that PRMT5 promoted CRC cell proliferation, migration and invasion in vitro and in vivo. We identified minichromosome maintenance‐7 (MCM7) as the direct PRMT5‐binding partner. A co‐immunoprecipitation (co‐IP) assay indicated that PRMT5 physically interacted with MCM7 and that the direct binding domain was located between residues 1‐248 in MCM7. In addition, our results from analysis of 99 CRC tissues and 77 adjacent non‐cancerous tissues indicated that the PRMT5 and MCM7 expression levels were significantly higher in CRC tissues than in control tissues, which was further confirmed by bioinformatic analysis using TCGA and GEO datasets. We also found that MCM7 promoted CRC cell proliferation, migration and invasion in vitro. Furthermore, we observed that increased PRMT5 expression predicted unfavourable patient survival in CRC patients and in the subgroup of patients with a tumour size of ≤5 cm. These data suggested that PRMT5 and MCM7 might be novel potential targets for the treatment of CRC.
Flexural strength and microhardness of bulk‐fill restorative materials
Authors: de Mendonça Beatriz Curvello , Soto‐Montero Jorge Rodrigo , de Castro Eduardo Fernandes , Pecorari Vanessa Gallego Arias , Rueggeberg Frederick Allen , Giannini Marcelo 
Published: March 2021

AbstractBackgroundBulk‐fill materials can facilitate the restorative procedure mainly for deep and wide posterior cavities. The purpose of this study was to evaluate flexural strength (biaxial flexural strength [BFS]) and microhardness (Knoop microhardness [KHN]) at different depths of bulk‐fill materials.MethodsFive bulk‐fill materials were tested: two light‐curable composite resins, one dual‐cure composite, one bioactive restorative, and a high‐viscosity glass ionomer. A conventional composite was used as control. BFS and KHN were tested at different depths. Data was analyzed by two‐ and one‐way ANOVAs, respectively and Tukey's post‐hoc (α=0.05).ResultsThe high‐viscosity glass ionomer material presented the lowest BFS at all depths. KHN for the two light‐curable and the dual‐cure bulk‐fill resin composites was reduced following an increase in restoration depth, while the conventional composite, the bioactive material, and the high‐viscosity glass ionomer were not affected.ConclusionThere are differences in the properties of the tested materials at 4 mm depth, showing that the studied properties of some materials vary according to the cavity depth, although the results are material dependent.Clinical SignificanceMechanical properties of light‐cured, bulk‐fill materials may be affected by inadequate polymerization. Clinicians should consider complementary strategies to achieve adequate polymerization at high‐increment depths.
RNA-Sequencing Reveals Differentially Expressed Rice Genes Functionally Associated with Defense against BPH and WBPH in RILs Derived from a Cross between RP2068 and TN1
Authors: Divya Dhanasekar , Sahu Nihar , Reddy P. Sairam , Nair Suresh , Bentur J. S. 
Published: March 2021

AbstractBackgroundRice is staple food for over two billion people. Planthoppers like BPH and WBPH occur together in most of rice growing regions across Asia and cause extensive yield loss by feeding and transmission of disease-causing viruses. Chemical control of the pest is expensive and ecologically disastrous; breeding resistant varieties is an acceptable option. But most of such efforts are focused on BPH with an assumption that these varieties will also be effective against WBPH. No critical studies are available to understand rice resistance, common or otherwise, against these two planthoppers.ResultsOur studies aimed to understand the defense mechanisms in rice line RP2068 against BPH and WBPH through RNA sequencing analysis of a RIL line TR3RR derived from the cross TN1 (susceptible) and RP2068 (resistant) after infestation with BPH or WBPH. Results revealed higher number of differentially expressed genes (DEGs) in BPH infested plants than in WBPH infested plants when compared with the uninfested plants. These DEGs could be grouped into UPUP, DNDN, UPDN and DNUP groups based on whether the DEGs were up (UP) or down (DN) regulated against BPH and WBPH, respectively. Gene ontology analysis, specially of members of the last two groups, revealed differences in plant response to the two planthoppers. Abundance of miRNAs and detection of their target genes also indicated that separate sets of genes were suppressed or induced against BPH and WBPH. These results were validated through the analysis of expression of 27 genes through semi-quantitative and quantitative real-time RT-PCR using a set of five RILs that were genetically identical but with different reaction against the two planthoppers. Coupled with data obtained through pathway analysis involving these 27 genes, expression studies revealed common and differential response of rice RP2068 against BPH and WBPH. Trehalose biosynthesis, proline transport, methylation were key pathways commonly upregulated; glucosinolate biosynthesis, response to oxidative stress, proteolysis, cytokinesis pathways were commonly down regulated; photosynthesis, regulation of transcription, expression and transport of peptides and defense related pathways were exclusively upregulated against WBPH; MYB transcription factor mediated defense induction was exclusive to BPH.ConclusionRice defense against the two sympatric planthoppers: BPH and WBPH has distinct features in RP2068. Hence, a conscious combination of resistance to these two pests is essential for effective field management.