bluuebunny/crossref_metadata_2025_split huggingface dataset:
The FW2.2/CNR protein regulates cell-to-cell communication in tomato by modulating callose deposition at plasmodesmata
Authors: Beauchet Arthur , Bollier Norbert , Grison Magali , Rofidal Valérie , Gévaudant Frédéric , Bayer Emmanuelle , Gonzalez Nathalie , Chevalier Christian 
Published: September 2023

AbstractTheFW2.2gene is the founding member of theCELL NUMBER REGULATOR(CNR) gene family. More than 20 years ago,FW2.2was the first cloned gene underlying a Quantitative Trait Locus (QTL) governing fruit size/weight in tomato. However, despite this discovery, the molecular mechanisms by which FW2.2 acts as a negative regulator of cell divisions during fruit growth remain undeciphered. In the present study, we confirm that FW2.2 is a transmembrane spanning protein, whose both N- and C-terminal ends are facing the apoplast. We unexpectedly found that FW2.2 is located at plasmodesmata (PD). FW2.2 participates in the spatiotemporal regulation of callose deposition at PD via an interaction with Callose Synthases, which suggests a regulatory role in cell-to-cell communication by modulating PD transport capacity and trafficking of signaling molecules during fruit development.
Leveraging GPT-4 for Identifying Cancer Phenotypes in Electronic Health Records: A Performance Comparison between GPT-4, GPT-3.5-turbo, Flan-T5 and spaCy’s Rule-based & Machine Learning-based methods
Authors: Bhattarai Kriti , Oh Inez Y. , Sierra Jonathan Moran , Tang Jonathan , Payne Philip R.O. , Abrams Zachary B. , Lai Albert M. 
Published: September 2023

ABSTRACTObjectiveAccurately identifying clinical phenotypes from Electronic Health Records (EHRs) provides additional insights into patients’ health, especially when such information is unavailable in structured data. This study evaluates the application of OpenAI’s Generative Pre-trained Transformer (GPT)-4 model to identify clinical phenotypes from EHR text in non-small cell lung cancer (NSCLC) patients. The goal was to identify disease stages, treatments and progression utilizing GPT-4, and compare its performance against GPT-3.5-turbo, Flan-T5-xl, Flan-T5-xxl, and two rule-based and machine learning-based methods, namely, scispaCy and medspaCy.Materials and MethodsPhenotypes such as initial cancer stage, initial treatment, evidence of cancer recurrence, and affected organs during recurrence were identified from 13,646 records for 63 NSCLC patients from Washington University in St. Louis, Missouri. The performance of the GPT-4 model is evaluated against GPT-3.5-turbo, Flan-T5-xxl, Flan-T5-xl, medspaCy and scispaCy by comparing precision, recall, and micro-F1 scores.ResultsGPT-4 achieved higher F1 score, precision, and recall compared to Flan-T5-xl, Flan-T5-xxl, medspaCy and scispaCy’s models. GPT-3.5-turbo performed similarly to that of GPT-4. GPT and Flan-T5 models were not constrained by explicit rule requirements for contextual pattern recognition. SpaCy models relied on predefined patterns, leading to their suboptimal performance.Discussion and ConclusionGPT-4 improves clinical phenotype identification due to its robust pre-training and remarkable pattern recognition capability on the embedded tokens. It demonstrates data-driven effectiveness even with limited context in the input. While rule-based models remain useful for some tasks, GPT models offer improved contextual understanding of the text, and robust clinical phenotype extraction.
Studies of DNA ‘breathing’ by polarization-sweep single-molecule fluorescence microscopy of exciton-coupled (iCy3)2dimer-labeled DNA fork constructs
Authors: Maurer Jack , Albrecht Claire S. , Herbert Patrick , Heussman Dylan , Chang Anabel , von Hippel Peter H. , Marcus Andrew H. 
Published: September 2023

AbstractLocal fluctuations of the sugar-phosphate backbones and bases of DNA (often called DNA ‘breathing’) play a variety of critical roles in controlling the functional interactions of the DNA genome with the protein complexes that regulate it. Here we present a single-molecule fluorescence method that we have used to measure and characterize such conformational fluctuations at and near biologically important positions in model DNA replication fork constructs labeled with exciton-coupled cyanine [(iCy3)2] dimer probes. Previous work has shown that the constructs that we test here exhibit a broad range of spectral properties at the ensemble level, and these differences can be structurally and dynamically interpreted using our present methodology at the single-molecule level. The (iCy3)2dimer has one symmetric (+) and one anti-symmetric (–) exciton with respective transition dipole moments oriented perpendicular to one another. We excite single molecule samples using a continuous-wave linearly polarized laser with polarization direction continuously rotated at the frequency 1 MHz. The ensuing fluorescence signal is modulated as the laser polarization alternately excites the symmetric and the anti-symmetric excitons of the (iCy3)2dimer probe. Phase-sensitive detection of the modulated signal provides information about the distribution of local conformations and conformational interconversion dynamics of the (iCy3)2probe. We find that at most construct positions that we examined the (iCy3)2dimer-labeled DNA fork constructs can adopt four topologically distinct conformational macrostates. These results suggest that in addition to observing DNA breathing at and near ss-dsDNA junctions, our new methodology should be useful to determine which of these pre-existing macrostates are recognized by, bind to, and are stabilized by various genome regulatory proteins.
Human vaginal microbiota colonization is regulated by female sex hormones in a mouse model
Authors: Rahman Nuzhat , Mian Firoz , Kaushic Charu 
Published: September 2023

AbstractClinically, aLactobacillusrich vaginal microbiota (VMB) is considered optimal for reproductive outcomes, while a VMB populated by anaerobes is associated with dysbiosis and the clinical condition bacterial vaginosis (BV), which is linked to increased susceptibility to sexually transmitted infections and adverse reproductive outcomes. Mouse models that mimic eubiotic and dysbiotic VMB are currently lacking but could play a critical role in improving protective interventions. In this study, probiotic, eubiotic, and dysbiotic models were first developed in normal mice, using probiotic strainsLactobacillus rhamnosusGR-1 andLactobacillus reuteriRC-14, eubioticLactobacillus crispatus, or dysbioticGardnerella vaginalisstrains. Following a single administration,L. rhamnosusandL. reuteripersisted in the mouse vaginal tract for up to eight days,L. crispatuspersisted for up to three days, andG. vaginalispersisted for up to two days, as measured by quantitative plating assays and qPCR. Colonization ofG. vaginaliswas facilitated by the presence of mucin. Endogenous sex hormones were manipulated by either ovariectomizing (OVX) mice or administering 17β-estradiol and progesterone pellets in OVX mice. The lack of endogenous hormones in OVX mice dramatically decreased VMB bacterial load compared to normal mice. None of the exogenous bacteria includingLactobacillicould colonize OVX mice for more than 24 hours. Treatment with 17β-estradiol but not progesterone restored the endogenous microbiota and colonization withLactobacilliandG. vaginalis. Interestingly, 17β-estradiol treated mice had significantly increased levels of glycogen, compared to OVX and progesterone-treated mice. These results suggest there is a dynamic interaction between sex hormones and the VMB, which can affect bacterial diversity and the ability for a VMB to colonize.
MultipleXed Population Selection and Enrichment single nucleus RNA sequencing (XPoSE-seq) enables sample identity retention during transcriptional profiling of rare populations
Authors: Savell Katherine E. , Madangopal Rajtarun , Saravanan Padmashri , Palaganas Ryan G. , Woods Kareem D. , Thompson Drake J. , Drake Olivia R. , Brenner Megan B. , Weber Sophia J. , Van Leer Elise , Choi Jae H. , Martin Toni L. , Martin Jody C. , Steinberg Mia K. , Austin James W. , Charendoff Chloé I. , Hope Bruce T. 
Published: September 2023

AbstractSingle nucleus RNA-sequencing is critical in deciphering tissue heterogeneity and identifying rare populations. However, current high throughput techniques are not optimized for rare target populations and require tradeoffs in design due to feasibility. We provide a novel snRNA pipeline, MulipleXedPopulationSelection andEnrichment snRNA-sequencing (XPoSE-seq), to enable targeted snRNA-seq experiments and in-depth transcriptomic characterization of rare target populations while retaining individual sample identity.
Tracking genome evolution in single cell clones reveals the rates and features of copy number alterations generated by ongoing chromosomal instability in cancer
Authors: Guscott Molly A. , Gómez-Peregrina David , Andersen Alexander Malling , Soliman Tanya N. , Horrach Caterina Vidal , Bakker Bjorn , Johanna Spierings Diana Carolina , Wardenaar René , Foijer Floris , Serrano Cesar , Schwarz Roland , McClelland Sarah E. 
Published: September 2023

AbstractCancer genomes exhibit extensive chromosomal alterations caused by ongoing Chromosomal Instability (CIN). The ensuing cell-cell heterogeneity facilitates evolution and cancer cell plasticity that can drive therapy resistance, yet cancer CIN driver mechanisms remain essentially uncharacterised. This lack of knowledge presents an untapped opportunity to target vulnerabilities associated with ongoing CIN for therapy. Existing methods to investigate the cellular mechanisms responsible for CIN rely on laborious functional assays, or inference from genomic alteration patterns from sequencing data. Current bulk sequencing derived copy number alteration pattern signatures lack the cell-cell resolution that would reveal recent genomic alterations caused by CIN. Large-scale single cell sequencing of cancer cell populations is now emerging. However, it is not known whether the effects of selection still obscure the spectrum of genomic alterations caused by recent CIN. To address this, we employed a single-cell whole-genome sequencing (scWGS) clonal outgrowth technique, that allows us to track the real-time evolution of cancer genomes at the single-cell level. Single cancer cells surprisingly re-establish heterogeneity that matches their parental population within ∼22 generations. By comparing the features of copy number alterations at different evolutionary timepoints we reveal that some alteration types are likely under negative selection and are thus only apparent in the most recent cell divisions, and not in the parental population. In one cell line we identify a particular chromosome subject to recurrent chromosomal deletions, and validated that this chromosome wasinvolved frequently in mis-segregation events during anaphase using fluorescenceIn-Situhybridisation.
Highly Robust DNA Data Storage Based on Controllable GC Content and homopolymer of 64-Element Coded Tables
Authors: Yunfei Lu , Xuncai Zhang 
Published: September 2023

AbstractIn this paper, we propose a DNA storage encoding scheme based on a 64-element coding table combined with forward error correction. The method encodes the data into DNA sequences by LZW compression of the original text, adding error correction codes and scrambling codes. In the encoding process, the effects of GC content limitation and long homopolymers on DNA sequences are considered. At the same time, RS error correction code is introduced to correct the DNA sequence to improve the accuracy of decoding. Finally, the feasibility and effectiveness of the program were verified by simulation experiments on Shakespeare’s sonnets. The data results show that the GC content of DNA sequences encoded by the program is kept at 50%, the homologous multimer length is not more than 2, and the original information can be recovered from the data of 10-fold sequencing depth without error with an error rate of 0.3%. We conducted simulation experiments of primer design, DNA sequence recombination, PCR amplification, and sequence reading on DNA sequences loaded with design information, which further proved the concrete feasibility of the scheme. This scheme provides a reliable and efficient encoding scheme for DNA information storage.
Germline mutations and developmental mosaicism underlyingEGFR-mutant lung cancer
Authors: Burr Risa , Leshchiner Ignaty , Costantino Christina L , Blohmer Martin , Sundaresan Tilak , Cha Justin , Seeger Karsen , Guay Sara , Danysh Brian P , Gore Ira , Jacobs Raquel A , Slowik Kara , Utro Filippo , Rhrissorrakrai Kahn , Levovitz Chaya , Barth Jaimie L , Dubash Taronish , Chirn Brian , Parida Laxmi , Sequist Lecia V , Lennerz Jochen K , Mino-Kenudson Mari , Maheswaran Shyamala , Naxerova Kamila , Getz Gad , Haber Daniel A 
Published: September 2023

AbstractWhile the development of multiple primary tumors in smokers with lung cancer can be attributed to carcinogen-induced field cancerization, the occurrence of multiple primary tumors in individuals withEGFR-mutant lung cancer who lack known environmental exposures remains unexplained. We identified ten patients with early-stage, resectable non-small cell lung cancer who presented with multiple anatomically distinctEGFR-mutant tumors. We analyzed the phylogenetic relationships among multiple tumors from each patient using whole exome sequencing (WES) and hypermutable poly-guanine (poly-G) repeat genotyping, as orthogonal methods for lineage tracing. In two patients, we identified germlineEGFRvariants, which confer moderately enhanced signaling when modeledin vitro. In four other patients, developmental mosaicism is supported by the poly-G lineage tracing and WES, indicating a common non-germline cell-of-origin. Thus, developmental mosaicism and germline variants define two distinct mechanisms of genetic predisposition to multipleEGFR-mutant primary tumors, with implications for understanding their etiology and clinical management.
Natriuretic Peptides Improve Classification of People at Low Risk of Atrial Fibrillation after Stroke
Authors: Cameron Alan , Arnold Markus , Katsas Georgios , Yang Jason , Quinn Terence J , Abdul-Rahim Azmil H , Campbell Ross , Docherty Kieran , De Marchis Gian Marco , Arnold Marcel , Kahles Timo , Nedeltchev Krassen , Cereda Carlo , Kaegi Georg , Bustamante Alejandro , Montaner Joan , Ntaios George , Foerch Christian , Spanaus Katharina , Von Eckardstein Arnold , Dawson Jesse , Katan Mira 
Published: September 2023

AbstractBackgroundProlonged cardiac monitoring (PCM) increases atrial fibrillation detection after stroke (AFDAS) but access is limited. We aimed to assess the utility of midregional pro-atrial natriuretic peptide (MR-proANP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) to identify people who are unlikely to have AFDAS and improve healthcare resource allocation for PCM..MethodsWe analysed people from the BIOSIGNAL (Biomarker Signature of Stroke Aetiology) study with ischaemic stroke, no known AF and ≥3 days cardiac monitoring. External validation was in the PRECISE (Preventing Recurrent Cardioembolic Stroke: Right Approach, Right Patient) study of 28-days cardiac monitoring after stroke.The main outcome is no AFDAS. We assessed the discriminatory value of MR-proANP and NT-proBNP combined with clinical variables to identify people with no AFDAS. We determined the net reduction in people who would undergo PCM using the models with 15% AFDAS threshold probability.ResultsWe included 621 people from BIOSIGNAL. The clinical model included age, National Institutes of Health Stroke Scale score, lipid-lowering therapy, creatinine and smoking status. The AUROC was 0.68 (95%CI 0.62-0.74) with clinical variables, which improved with log10MR-proANP (0.72,0.66-0.78;p=0.001) or log10NT-proBNP (0.71,0.65-0.77;p=0.009). Performance was similar for log10MR-proANP versus log10NT-proBNP (p=0.28).In 239 people from PRECISE, the AUROC for clinical variables was 0.68 (0.59-0.76), which improved with log10NT-proBNP (0.73,0.65-0.82;p<0.001) or log10MR-proANP (0.79,0.72-0.86;p<0.001). Performance was better with log10MR-proANP versus log10NT-proBNP (p=0.03).The models could reduce the number who would undergo PCM by 30% (clinical+log10MR-proANP), 27% (clinical+log10NT-proBNP) or 20% (clinical).ConclusionsMR-proANP and NT-proBNP help classify people who are unlikely to have AFDAS and could reduce the number who need PCM by 30%.
Beneficial metabolic effects of PAHSAs depend on the gut microbiota in diet-induced obese mice
Authors: Lee Jennifer , Wellenstein Kerry , Rahnavard Ali , Nelson Andrew T. , Holter Marlena M. , Cummings Bethany , Yeliseyev Vladimir , Castoldi Angela , Clish Clary B. , Bry Lynn , Siegel Dionicio , Kahn Barbara B. 
Published: September 2023

ABSTRACTDietary lipids play an essential role in regulating the function of the gut microbiota and gastrointestinal tract, and these luminal interactions contribute to mediating host metabolism. PAHSAs are a class of lipids with anti-diabetic and anti-inflammatory properties, but whether the gut microbiota contributes to their beneficial effects on host metabolism is unknown. Here, we report that treating high fat diet (HFD)-fed germ-free mice with PAHSAs does not improve insulin sensitivity. However, transfer of feces from PAHSA-treated, but not Vehicle-treated, chow-fed mice increases insulin-sensitivity in HFD-fed germ free mice. Thus, the gut microbiota is necessary for and can transmit the insulin-sensitizing effects of PAHSAs in HFD-fed germ-free mice. Functional analyses of the cecal metagenome and lipidome of PAHSA-treated mice identified multiple lipid species that associate with the gut commensalBacteroides thetaiotaomicron(Bt) and with insulin sensitivity resulting from PAHSA treatment.Btsupplementation in HFD-fed female mice prevented weight gain, reduced adiposity, improved glucose tolerance, fortified the colonic mucus barrier and reduced systemic inflammation versus chow-fed controls, effects that were not observed in HFD-fed male mice. Furthermore, ovariectomy partially reversed the beneficialBteffects on host metabolism, indicating a role for sex hormones in mediating probiotic effects. Altogether, these studies highlight the fact that lipids can modulate the gut microbiota resulting in improvement in host metabolism and that PAHSA-induced changes in the microbiota result in at least some of their insulin-sensitizing effects in female mice.
Enhanced spine stability and survival lead to increases in dendritic spine density as an early response to local alpha-synuclein overexpression in mouse prefrontal cortex
Authors: Bosch Peter J. , Kerr Gemma , Cole Rachel , Warwick Charles A. , Wendt Linder H , Pradeep Akash , Bagnall Emma , Aldridge Georgina M. 
Published: September 2023

AbstractLewy Body Dementias (LBD), including Parkinson’s disease dementia and Dementia with Lewy Bodies, are characterized by widespread accumulation of intracellular alpha-Synuclein protein deposits in regions beyond the brainstem, including in the cortex. Patients with LBDs develop cognitive changes, including abnormalities in executive function, attention, hallucinations, slowed processing, and cognitive fluctuations. The causes of these non-motor symptoms remain unclear; however, accumulation of alpha-Synuclein aggregates in the cortex and subsequent interference of synaptic and cellular function could contribute to psychiatric and cognitive symptoms. It is unknown how the cortex responds to local pathology in the absence of significant secondary effects of alpha-Synuclein pathology in the brainstem. To investigate this, we employed viral overexpression of human alpha-Synuclein protein targeting the mouse prefrontal cortex (PFC). We then usedin vivo2-photon microscopy to image awake head-fixed mice via an implanted chronic cranial window to assess the early consequences of alpha-Synuclein overexpression in the weeks following overexpression. We imaged apical tufts of Layer V pyramidal neurons in the PFC ofThy1-YFPtransgenic mice at 1-week intervals from 1-2 weeks before and 9 weeks following viral overexpression, allowing analysis of dynamic changes in dendritic spines. We found an increase in the relative dendritic spine density following local overexpression of alpha-Synuclein, beginning at 5 weeks post-injection, and persisting for the remainder of the study. We found that alpha-Synuclein overexpression led to an increased percentage and longevity of newly-persistent spines, without significant changes in the total density of newly formed or eliminated spines. A follow up study utilizing confocal microscopy revealed that the increased spine density is found in cortical cells within the alpha-Synuclein injection site, but negative for alpha-Synuclein phosphorylation at Serine-129, highlighting the potential for effects of dose and local circuits on spine survival. These findings have important implications for the physiological role and early pathological stages of alpha-Synuclein in the cortex.
Engineered bacteria launch and control an oncolytic virus
Authors: Singer Zakary S. , Pabón Jonathan , Huang Hsinyen , Sun William , Luo Hongsheng , Grant Kailyn Rhyah , Obi Ijeoma , Coker Courtney , Rice Charles M , Danino Tal 
Published: September 2023

AbstractThe ability of bacteria and viruses to selectively replicate in tumors has led to synthetic engineering of new microbial therapies. Here we design a cooperative strategy wherebyS. typhimuriumbacteria transcribe and deliver the Senecavirus A RNA genome inside host cells, launching a potent oncolytic viral infection. “Encapsidated” by bacteria, the viral genome can further bypass circulating antiviral antibodies to reach the tumor and initiate replication and spread within immune mice. Finally, we engineer the virus to require a bacterially delivered protease to achieve virion maturation, demonstrating bacterial control over the virus. This work extends bacterially delivered therapeutics to viral genomes, and shows how a consortium of microbes can achieve a cooperative aim.
The impact of HTLV-1 expression on the 3D structure and expression of host chromatin
Authors: Yaguchi Hiroko , Melamed Anat , Ramanayake Saumya , Kiik Helen , Witkover Aviva , Bangham Charles R M 
Published: September 2023

AbstractA typical HTLV-1-infected individual carries >104different HTLV-1-infected T cell clones, each with a single-copy provirus integrated in a unique genomic site. We previously showed that the HTLV-1 provirus causes aberrant transcription in the flanking host genome and, by binding the chromatin architectural protein CTCF, forms abnormal chromatin loops with the host genome. However, it remained unknown whether these effects were exerted simply by the presence of the provirus or were induced by its transcription. To answer this question, we sorted HTLV-1-infected T-cell clones into cells positive or negative for proviral plus-strand expression, and then quantified host and provirus transcription using RNA-seq and aberrant chromatin looping using quantitative chromosome conformation capture (q4C) in each cell population. We found that proviral plus-strand transcription induces aberrant transcription and splicing in the flanking genome but suppresses aberrant chromatin loop formation with the nearby host chromatin. Reducing provirus-induced host transcription with an inhibitor of transcriptional elongation allows recovery of chromatin loops in the plus-strand-expressing population. We conclude that aberrant host transcription induced by proviral expression causes temporary, reversible disruption of chromatin looping in the vicinity of the provirus.