bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinal Disease Early Detection using Deep Learning on Ultra-wide-field Fundus Images
Authors: Nguyen Toan Duc , Jung Kyunghee , Bui Phuoc-Nguyen , Pham Van-Nguyen , Bum Junghyun , Le Duc-Tai , Kim Seongho , Song Su Jeong , Choo Hyunseung 
Published: March 2023

AbstractUltra-wide-field Fundus Imaging captures the main components of a patient’s eyes such as optic dics, fovea and macula, providing doctors with a profound and precise observation, allowing diagnosis of diseases with appropriate treatment. In this study, we exploit and compare deep learning models to detect eye disease using Ultra-wide-field Fundus Images. To fulfil this, a fully-automated system is brought about which pre-process and amplify 4697 images using cutting-edge computer vision techniques with deep neural networks. These neural networks are state-of-the-art methods in modern artificial intelligence system combined with transfer learning to learn the best representation of medical images. Overall, our system is composed of 3 main steps: data augmentation, data pre-processing and classification. Our system demonstrates that ResNet152 achieved the best results amongst the models, with the area under the curve (AUC) score of 96.47% (95% confidence interval (CI), 0.931-0.974). Furthermore, we visualise the prediction of the model with the corresponding confidence score and provide the heatmaps which show the focal point focused by the models, where the lesion exists in the eye because of damage. In order to help the ophthalmologists in their assessment, our system is an essential tool to speed up the process as it can automate diagnosing procedures and giving detailed predictions without human interference. Through this work, we show that Ultra-wide-field Images are feasible and applicable to be used with deep learning.
Sophisticated Prediction of Carotid-Plaque Vulnerability by Nanocluster Sensitized High-resolution Vessel-Wall-Imaging Profile in Rabbit Atherosclerotic Model
Authors: Gong Yan , Wu Menglin , Fu Dingwei , Guo Yu , Lu Xiudi , Zou Ying , Zhang Xiang , Zhu Jinxia , Zhang Xianchang , Li Xue , Xia Shuang 
Published: March 2023

AbstractOBJECTIVETo innovatively developed a macrophage-target nanoparticle based contrast-enhanced high-resolution magnetic resonance vessel wall imaging (HR-VWI) strategy to characterize the plaques’ vulnerable features on rabbits.BACKGROUNDLacking of sensitive and specific image-marker of HR-VWI leads this technique depending upon the plaque morphological characteristics. Nanoparticle-based contrast agents modified with targeting ligands allow amplifying MR signals of the interested components. The key to successful translation is the requirement that conducting studies in larger animals to provide reasonable diagnostic readouts.METHODSThe HR-VWI enhanced with macrophage-targeted PP1-Au@GSH@Gd (GdMG) nanoclusters (NCs) and the conventional Gadovist were utilized for the plaque vulnerability evaluation by a systematic histogram analysis in atherosclerosis (AS) rabbit model.RESULTSDue to the compelling targeting capacity of GdMG NCs to foamy macrophages, the contrast-to-noise ratio (CNR) from pre-injection baseline dramatically raised from 6.50 to 36.91 (p< 0.001), with an increment of 1.39-fold higher than that of the Gadovist approach. Spearman’ s correlation test confirmed that the coefficient of variation (CV) derived from the histogram analysis based on GdMG NCs HR-VWI was indeed positively linearly correlated with pathology vulnerability index (VIP) significantly (p< 0.05) with adjusted R2= 0.775. Finally, mathematic formulas with histogram-derived parameters as variables were fitted to quantitatively calculate the histogram vulnerability index (VIH) with the strength of the adjusted R2= 0.952 (p< 0.001), and Area under the curve (AUC) of 0.875 (p< 0.001) to realize thein vivoand quantitative calculation of the plaque vulnerability.CONCLUSIONProfiting from the splendid inflammation targeted capacity and excellent MRI performance of GdMG NCs, as well as the highly quantitative characteristics of histogram analysis, we disclosed that our established imaging protocol was able to identify the plaques’ vulnerability index that were comparable to pathological examinations in both retrospective and prospective experiments.
An efficient error correction and accurate assembly tool for noisy long reads
Authors: Hu Jiang , Wang Zhuo , Sun Zongyi , Hu Benxia , Ayoola Adeola Oluwakemi , Liang Fan , Li Jingjing , Sandoval José R. , Cooper David N. , Ye Kai , Ruan Jue , Xiao Chuan-Le , Wang De-Peng , Wu Dong-Dong , Wang Sheng 
Published: March 2023

AbstractLong read sequencing data, particularly those derived from the Oxford Nanopore (ONT) sequencing platform, tend to exhibit a high error rate. Here, we present NextDenovo, a highly efficient error correction and assembly tool for noisy long reads, which achieves a high level of accuracy in genome assembly. NextDenovo can rapidly correct reads; these corrected reads contain fewer errors than other comparable tools and are characterized by fewer chimeric alignments. We applied NextDenovo to the assembly of high quality reference genomes of 35 diverse humans from across the world using ONT Nanopore long read sequencing data. Based on thesede novogenome assemblies, we were able to identify the landscape of segmental duplications and gene copy number variation in the modern human population. The use of the NextDenovo program should pave the way for population-scale long-read assembly, thereby facilitating the construction of human pan-genomes, using Nanopore long read sequencing data.
Unravelling bird nest arthropod community structure using metabarcoding
Authors: Levesque-Beaudin Valerie , Steinke Dirk , Böcker Mieke , Thalinger Bettina 
Published: March 2023

AbstractBird nests are fascinating microcosms harboring a wide range of arthropods parasitizing the nesting birds or feeding on prey remains, feces, and the nest material. Studies of these communities have been entirely based on emergence traps which collect live organisms out of the nests. The analysis of nest contents and environmental DNA (eDNA) via metabarcoding could expand our knowledge and identify prey, exuviae, and other animal remains in bird nests.Here, we investigated the potential of arthropod remains, nest dust, and feathers to better describe taxonomic diversity accumulated in 20 bird nests collected in Guelph (Canada). We used subsampling strategies and tested two extraction approaches to investigate the distribution of DNA in nests, account for low-quality DNA, and the presence of inhibitory substances.In total, 103 taxa were detected via metabarcoding. Arthropod remains delivered the highest number of taxa (n=67), followed by nest dust (n=29). Extractions with the PowerSoil kit outperformed DNeasy extractions coupled with PowerClean Pro inhibitor removal. The subsamples of the same nest showed 5.5% and 47.1% taxonomic overlap for arthropod remains and PowerSoil extracted nest dust, respectively, indicating a heterogeneous eDNA distribution in nests. Most detected species were either feeding in the nest, i.e., herbivorous / predatory, or bird food. We also detected molecular traces of 25 bird species, whose feathers were likely used as nest material.Consequently, the metabarcoding of bird nest materials provides a more complete picture of nest communities, which can enable future studies on functional diversity and better comparisons between nesting species.
Arabidopsis calmodulin-like proteins CML13 and CML14 interact with proteins that have IQ domains
Authors: Teresinski Howard J. , Hau Bryan , Symonds Kyle , Kilburn Ryan , Munro Kim A. , Doner Nathan M. , Mullen Robert , Li Vivian H. , Snedden Wayne A. 
Published: March 2023

SUMMARYIn response to Ca2+signals, the evolutionarily-conserved Ca2+sensor calmodulin (CaM) regulates protein targets via direct interaction. Plants possess many CaM-like (CML) proteins, but their binding partners and functions are mostly unknown. Here, using Arabidopsis CML13 as ‘bait’ in a yeast two-hybrid screen, we isolated putative targets from three, unrelated protein families, namely, IQD proteins, calmodulin-binding transcriptional activators (CAMTAs), and myosins, all of which possess tandem isoleucine-glutamine (IQ) structural domains. Using the split-luciferase complementation assayin plantaand the yeast 2-hybrid system, CML13 and CML14 showed a preference for interaction with tandem over single IQ domains. Relative to CaM, CML13 and CML14 displayed weaker signals when tested with the non-IQ, CaM-binding domain of glutamate decarboxylase or the single IQ domains of CNGC20 (cyclic-nucleotide gated channel-20) or IQM1 (IQ motif protein1). We examined IQD14 as a representative tandem IQ-protein and found that only CaM, CML13, and CML14 interacted with IQD14 among 12 CaM/CMLs tested. CaM, CML13, and CML14 boundin vitroto IQD14 in the presence or absence of Ca2+. Binding affinities were in the nM range and were higher when two tandem IQ domains from IQD14 were present. Green fluorescent protein-tagged versions of CaM, CML13, and CML14 localized to both the cytosol and nucleus in plant cells but were partially relocalized to the microtubules when co-expressed with IQD14 tagged with mCherry. These and other data are discussed in the context of possible roles for these CMLs in gene regulation via CAMTAs and cytoskeletal activity via myosins and IQD proteins.
Transcription factor GLK2 regulates key steps of anthocyanin biosynthesis to antagonize photo-oxidative stress during greening of Arabidopsis seedlings
Authors: Zeng Xiyu , Ye Luhuan , Zhang Rui , Wang Peng 
Published: March 2023

AbstractThe greening of young seedling is light induced but vulnerable to photo-oxidative stress at the same time, due to the immature status of chloroplasts. Accumulation of anthocyanin is a protective response to high light, by absorbing excess energy and serving as antioxidant. In this work with Arabidopsis, we found that GARP family transcription factors GOLDEN2-LIKE 2 (GLK2), as a key regulator to chloroplast development, also plays an intensive role in regulating anthocyanin biosynthesis during seedling de-etiolation, especially under high light stress. We demonstrate that GLK2 positively regulates anthocyanin biosynthesis by directly activating the transcription of anthocyanin late biosynthetic genes (LBGs) as well asTRANSPARENT TESTA GLABRA 1(TTG1) gene, which encodes a key component of the regulatory MYB–bHLH–WDR (MBW) complex (which also activates LBGs). Our data further show that GLK2 and MBW each could activate the expression ofDFRgene (key LBG) independently, via distinct promoter regions. We therefore propose a multifaceted involvement of GLK2 in anthocyanin biosynthesis as an important protective measure for developing chloroplasts, against excessive light exposure during seedling photomorphogenesis.
Stabilization of Interdomain Interactions in G protein αiSubunits Determines GαiSubtype Signaling Specificity
Authors: Lefevre Tyler J. , Wei Wenyuan , Mukhaleva Elizaveta , Venkata Sai Pranathi Meda , Chandan Naincy R. , Abraham Saji , Li Yong , Dessauer Carmen W. , Vaidehi Nagarajan , Smrcka Alan V. 
Published: March 2023

AbstractHighly homologous members of the Gαifamily, Gαi1-3, have distinct tissue distributions and physiological functions, yet the functional properties of these proteins with respect to GDP/GTP binding and regulation of adenylate cyclase are very similar. We recently identified PDZ-RhoGEF (PRG) as a novel Gαi1effector, however, it is poorly activated by Gαi2. Here, in a proteomic proximity labeling screen we observed a strong preference for Gαi1relative to Gαi2with respect to engagement of a broad range of potential targets. We investigated the mechanistic basis for this selectivity using PRG as a representative target. Substitution of either the helical domain (HD) from Gαi1into Gαi2or substitution of a single amino acid, A230 in Gαi2to the corresponding D in Gαi1, largely rescues PRG activation and interactions with other Gαitargets. Molecular dynamics simulations combined with Bayesian network models revealed that in the GTP bound state, dynamic separation at the HD-Ras-like domain (RLD) interface is prevalent in Gαi2relative to Gαi1and that mutation of A230s4h3.3to D in Gαi2stabilizes HD-RLD interactions through formation of an ionic interaction with R145HD.11in the HD. These interactions in turn modify the conformation of Switch III. These data support a model where D229s4h3.3in Gαi1interacts with R144HD.11stabilizes a network of interactions between HD and RLD to promote protein target recognition. The corresponding A230 in Gαi2is unable to form the “ionic lock” to stabilize this network leading to an overall lower efficacy with respect to target interactions. This study reveals distinct mechanistic properties that could underly differential biological and physiological consequences of activation of Gαi1or Gαi2by GPCRs.
Generating high quality reference genomes from field collected specimens by optimizing preservation
Authors: Minich Jeremiah J , Moore Malia L , Allsing Nicholas A , Murray Emily R , Tran Loi , Michael Todd P 
Published: March 2023

AbstractSample preservation challenges efforts to generate high-quality reference genomes or pangenomes for all 2 million+ plant and animal species. Here we show 95% ethanol protects against degradation for fish blood (22°C, ≤6 weeks) and plant tissue (4°C, ≤3 weeks). Using Nanopore, we assemble high quality reference genomes from three fish and two plant species (contig N50: 6.5-13.8Mb; BUSCO completeness: 94.4-99.2%; QV: 43.8 forM. esculenta).
Efferocytosis-Induced Lactate Enables the Proliferation of Pro-Resolving Macrophages to Mediate Tissue Repair
Authors: Ngai David , Schilperoort Maaike , Tabas Ira 
Published: March 2023

AbstractThe clearance of apoptotic cells (ACs) by macrophages (efferocytosis) promotes tissue repair by preventing necrosis and inflammation and by activating pro-resolving pathways, including continual efferocytosis. A key resolution processin vivois efferocytosis-induced macrophage proliferation (EIMP), in which AC-derived nucleotides trigger Myc-mediated macrophage proliferation, thereby increasing the pool of efferocytosis-competent macrophages. Here we show that EIMP requires a second input that is integrated with cellular metabolism, notably, efferocytosis-induced lactate production. While the AC-nucleotide pathway leads to induction ofMycmRNA, lactate signaling is required for the stabilization of Myc protein and subsequent macrophage proliferation. Lactate, via GPR132 and protein kinase A, activates AMP kinase, which increases the NAD+:NADH ratio. This upstream pathway then activates the NAD+-dependent protein deacetylase, SIRT1, which deacetylates Myc to promote its stabilization. Inhibition or silencing of any step along this pathway prevents the increase in Myc protein and proliferation in efferocytosing macrophages despite the presence of the AC-nucleotide/MycmRNA pathway. To test importancein vivo, we transplanted mice with bone marrow cells in which the lactate biosynthetic enzyme lactate dehydrogenase A (LDHA) was knocked down. We then subjected these mice and control bone marrow-transplanted mice to dexamethasone-induced thymocyte apoptosis, a model of high-AC burden. The thymi of the LDHA-knockdown cohort showed reduced macrophage Myc protein expression and proliferation, impaired AC clearance, and increased tissue necrosis. Thus, efferocytosis-induced macrophage proliferation, which is a key process in tissue resolution, requires inputs from two independent efferocytosis-induced processes: a signaling pathway induced by AC-derived nucleotides and a cellular metabolism pathway involving lactate production. These findings illustrate how seemingly distinct pathways in efferocytosing macrophages are integrated to carry out a key process in tissue resolution.
Panpipes: a pipeline for multiomic single-cell and spatial transcriptomic data analysis
Authors: Curion Fabiola , Rich-Griffin Charlotte , Agarwal Devika , Ouologuem Sarah , Thomas Tom , Theis Fabian J. , Dendrou Calliope A. 
Published: March 2023

AbstractSingle-cell multiomic analysis of the epigenome, transcriptome and proteome allows for comprehensive characterisation of the molecular circuitry that underpins cell identity and state. However, the holistic interpretation of such datasets presents a challenge given a paucity of approaches for systematic, joint evaluation of different modalities. Here, we present Panpipes, a set of computational workflows designed to automate multimodal single-cell and spatial transcriptomic analyses by incorporating widely-used Python-based tools to perform quality control, preprocessing, integration, clustering, and reference mapping at scale. Panpipes allows reliable and customisable analysis and evaluation of individual and integrated modalities, thereby empowering decision-making before downstream investigations.
Itaconate promotes the differentiation of murine stress erythroid progenitors by increasing Nrf2 activity
Authors: Ruan Baiye , Chen Yuanting , Trimidal Sara , Koo Imhoi , Cai Jingwei , Mcguigan John , Hall Molly A. , Patterson Andrew D. , Prabhu K. Sandeep , Paulson Robert F. 
Published: March 2023

AbstractSteady state erythropoiesis produces new erythrocytes at a constant rate to replace senescent erythrocytes removed in the spleen and liver. Inflammation caused by infection or tissue damage skews bone marrow hematopoiesis, increasing myelopoiesis at the expense of steady state erythropoiesis. To compensate for the loss of production, stress erythropoiesis is induced. Stress erythropoiesis is highly conserved between mouse and human but utilizes a different strategy than steady state erythropoiesis. Inflammatory signals promote the proliferation of immature stress erythroid progenitors (SEPS), which in response to erythropoietin and other signals transition to stress erythroid progenitors committed to differentiation. Here we show that TNFα dependent signaling increases ROS in SEPs during the proliferation stage, however, blocking ROS production impairs their later differentiation. In addition to TNFα, nitric oxide dependent signaling drives the proliferation of stress erythroid progenitors and production of nitric oxide must be decreased so that the progenitor cells can differentiate. As progenitor cells transition to differentiation, increased production of the anti-inflammatory metabolite itaconate activates Nfe2l2 or Nrf2, which inhibits Nos2 expression, leading to decreased nitric oxide production. Mutation of Irg1, the enzyme that catalyzes the production of itaconate, causes a delayed recovery from inflammatory anemia induced by heat killedBrucella abortus. Loss of itaconate-dependent activation of Nrf2 is rescued in vivo by IL-10, which leads to activation of Nrf2 and differentiation. These data show that the differentiation of stress erythroid progenitors relies on a switch to an anti-inflammatory metabolism and increased expression of pro-resolving cytokines.Key points1.The transition to differentiation of stress erythroid progenitors requires anti-inflammatory signals.2.The anti-inflammatory metabolite itaconate and IL-10 increase Nrf2 activity to promote the differentiation of stress erythroid progenitors.
Co-evolution of ion channels and neurotoxins in cnidarians leads to diversification of ion channel genes
Authors: Guruacharya Anuj 
Published: March 2023

ABSTRACTUnderstanding the diversity of ion channels in cnidarians may shed light on the origin and evolution of early nervous systems. It is hypothesized that cnidarian neurotoxins led to the evolution of diverse ion channel proteins in cnidarians. I tested this hypothesis by investigating several evolutionary factors of both cnidarian neurotoxins and their target ion channels. I examined homologs of 250 cnidarian toxins, 75 ion channel genes, and 70 housekeeping genes from 37 transcriptomes/genomes of cnidarian species. Analysis on the presence or absence of genes by species, selection analysis, and evolutionary rate analysis were performed on the homologs of neurotoxin and ion channel proteins. I found evidence of positive selection, correlation between the number of homologous gene families, and difference in the evolutionary rates among the gene families. I have shown for the first time that neurotoxins may have coevolved with the ion channels in cnidarians. This is consistent with an evolutionary arms race between ion channels and neurotoxins leading to extensive diversity of ion channel genes found in cnidarians.
Efficient characterization of multiple binding sites of small molecule imaging ligands on amyloid-beta, 4-repeat/full-length tau and alpha-synuclein
Authors: Sobek Jens , Li Junhao , Combes Benjamin F. , Gerez Juan A , Nilsson Peter K. , Henrich Martin T. , Geibl Fanni F. , Shi Kuangyu , Rominger Axel , Oertel Wolfgang H. , Nitsch Roger M. , Nordberg Agneta , Ågren Hans , Riek Roland , Ni Ruiqing 
Published: March 2023

AbstractAimThere is an unmet need for compounds that detect alpha-synuclein (αSyn) and 4-repeat tau, which are critical in many neurodegenerative diseases for diagnostic and therapeutic purposes. Here, we aim to develop an efficient surface plasmon resonance (SPR)-based method to facilitate the characterization of small molecule ligands/compounds to these fibrils.MethodsSPR measurements were conducted to characterize the binding properties of fluorescent ligands/compounds towards recombinant Aβ42, K18 4-repeat/full-length tau and αSyn fibrils. In silico modelling was performed to examine the binding pockets of ligands on αSyn fibrils. Immunofluorescence staining with fluorescence ligands and specific antibodies on postmortem brain tissue slices from patients with Parkinson’s disease and disease mouse models was performed.ResultsWe optimized the protocol for immobilizing Aβ42, K18 tau, full-length tau and αSyn fibrils in a controlled aggregation state on SPR sensor chips. The results from the analysis of binding kinetics suggested the presence of at least two binding sites for all fibrils, including luminescent conjugated oligothiophenes (HS-169, HS-84, h-FTAA and q-FTAA), pyridine derivative PBB5, nonfluorescent methylene blue and lansoprazole. In silico modelling studies for αSyn (6H6B) showed four binding sites with preference to S4. Immunofluorescence staining validated the detection of pS129-positive αSyn in brain tissue from Parkinson’s disease patients, αSyn PFF-injected mice, 6E10-positive Aβ in arcAβ mice, and AT-8/AT-100-positive in tau pR5 tau mice, respectively.ConclusionsSPR measurements of ligands and small molecules binding to Aβ42, 4R and full-length tau and αSyn fibrils suggest the existence of multiple binding sites. This approach may provide efficient characterization of compound binding properties towards these fibrils important in neurodegenerative diseases.