bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced prefrontal nicotinic signaling as evidence of active compensation in Alzheimer’s disease models
Authors: Power Saige K , Venkatesan Sridevi , Qu Sarah , McLaurin JoAnne , Lambe Evelyn K 
Published: November 2023

AbstractBackgroundCognitive reserve allows for resilience to neuropathology, potentially through active compensation. Here, we examineex vivoelectrophysiological evidence for active compensation in Alzheimer’s disease (AD) focusing on the cholinergic innervation of layer 6 in prefrontal cortex. Cholinergic pathways are vulnerable to neuropathology in AD and its preclinical models, and their modulation of deep layer prefrontal cortex is essential for attention and executive function.MethodsWe functionally interrogate cholinergic modulation of prefrontal layer 6 pyramidal neurons in two preclinical models: a compound transgenic AD mouse that permits optogenetically-triggered release of endogenous acetylcholine and a transgenic AD rat that closely recapitulates the human trajectory of AD. We then tested the impact of therapeutic interventions to further amplify the compensated responses and preserve the typical kinetic profile of cholinergic signaling.ResultsIn two AD models, we find a potentially-compensatory upregulation of functional cholinergic responses above non-transgenic controls after onset of pathology. To identify the locus of this enhanced cholinergic signal, we dissect key pre– and post-synaptic components with pharmacological strategies. We identify a significant and selective increase in post-synaptic nicotinic receptor signalling on prefrontal cortical neurons. To probe the additional impact of therapeutic intervention on the adapted circuit, we test cholinergic and nicotinic-selective pro-cognitive treatments. The inhibition of acetylcholinesterase further enhances endogenous cholinergic responses but greatly distorts their kinetics. Positive allosteric modulation of nicotinic receptors, by contrast, enhances endogenous cholinergic responses and retains their rapid kinetics.ConclusionsWe demonstrate that functional nicotinic upregulation occurs within the prefrontal cortex in two AD models. Promisingly, this nicotinic signal can be further enhanced while preserving its rapid kinetic signature. Taken together, our work suggests compensatory mechanisms are active within the prefrontal cortex that can be harnessed by nicotinic receptor positive allosteric modulation, highlighting a new direction for cognitive treatment in AD neuropathology.
Genetic factors acting prior to dormancy in sour cherry influence bloom time the following spring
Authors: Goeckeritz Charity Z. , Grabb Chloe , Grumet Rebecca , Iezzoni Amy F. , Hollender Courtney A. 
Published: November 2023

ABSTRACTBloom time is central to tree fruit production, and forPrunusspecies floral development leading up to bloom spans four seasons. Understanding this entire process is crucial for developing strategies to manipulate bloom time to prevent crop loss due to climate change. Here, we present a detailed examination of flower development from initiation until bloom for early- and late-blooming sour cherries (Prunus cerasus) from a population segregating for a major bloom time QTL on chromosome 4. Using a new staging system, we identified floral buds from early-blooming trees were persistently more advanced than those from late-blooming siblings. A gDNA coverage analysis revealed the late-blooming haplotype of this QTL,k, is located on a subgenome originating from the late-bloomingP. fruticosaprogenitor. Transcriptome analyses identified a large number of genes within this QTL as differentially expressed between early- and late-blooming trees during the vegetative-to-floral transition. From these, we identified candidate genes for the late bloom phenotype, including multiple transcription factors homologous to REproductive Meristem (REM) B3 domain-containing proteins. Additionally, we determined the basis ofkin sour cherry is likely separate from candidate genes found in sweet cherry – suggesting several major regulators of bloom time are located onPrunuschromosome 4.HIGHLIGHTDormancy is a main effector of bloom time in fruit trees. However, developmental, genetic, and transcriptomic analyses indicate differences in flower development before dormancy significantly influence flowering time in cherry.
Single cell spatial transcriptomic profiling of childhood-onset lupus nephritis reveals complex interactions between kidney stroma and infiltrating immune cells
Authors: Danaher Patrick , Hasle Nicholas , Nguyen Elizabeth D. , Hayward Kristen , Rosenwasser Natalie , Alpers Charles E. , Reed Robyn C. , Okamura Daryl M. , Baxter Sarah K. , Jackson Shaun W. 
Published: November 2023

AbstractChildren with systemic lupus erythematosus (SLE) are at increased risk of developing kidney disease, termed childhood-onset lupus nephritis (cLN). Single cell transcriptomics of dissociated kidney tissue has advanced our understanding of LN pathogenesis, but loss of spatial resolution prevents interrogation of in situ cellular interactions. Using a technical advance in spatial transcriptomics, we generated a spatially resolved, single cell resolution atlas of kidney tissue (>400,000 cells) from eight cLN patients and two controls. Annotated cells were assigned to 35 reference cell types, including major kidney subsets and infiltrating immune cells. Analysis of spatial distribution demonstrated that individual immune lineages localize to specific regions in cLN kidneys, including myeloid cells trafficking to inflamed glomeruli and B cells clustering within tubulointerstitial immune hotspots. Notably, gene expression varied as a function of tissue location, demonstrating how incorporation of spatial data can provide new insights into the immunopathogenesis of SLE. Alterations in immune phenotypes were accompanied by parallel changes in gene expression by resident kidney stromal cells. However, there was little correlation between histologic scoring of cLN disease activity and glomerular cell transcriptional signatures at the level of individual glomeruli. Finally, we identified modules of spatially-correlated gene expression with predicted roles in induction of inflammation and the development of tubulointerstitial fibrosis. In summary, single cell spatial transcriptomics allows unprecedented insights into the molecular heterogeneity of cLN, paving the way towards more targeted and personalized treatment approaches.
The effects of paroxetine-induced transient apoptosis and brain remodeling on social behavior in developing zebrafish
Authors: Sato Tomomi , Saito Kaito , Oyu Tsubasa , Tsuda Sachiko , Kurisaki Tomohiro , Kajihara Takeshi , Nagashima Masabumi 
Published: November 2023

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental condition caused by various genetic and environmental factors. This disorder has the cardinal symptoms including impaired social behavior involving the amygdala. Antidepressants such as paroxetine in early pregnancy increase the risk of ASD in offspring. However, a comprehensive picture of the underlying pathogenic mechanisms remains elusive. Here, we demonstrate that early exposure of zebrafish embryos to paroxetine suppresses neurogenesis in the optic tectum and the dorsal telencephalon which corresponds to the human amygdala. Paroxetine-treated embryos exhibit impaired growth, with small heads and short body lengths resulting from transient apoptosis. This is reminiscent of the early-onset fetal growth restriction (FGR) associated with ASD. Interestingly, the suppressed neurogenesis in the small heads was found to be restored after the cessation of paroxetine. This was accompanied by extended retinotectal projections, suggesting brain-preferential remodeling. Finally, the paroxetine-treated fish exhibited impaired social behavior, further supporting the correspondence with ASD. Our findings offer new insights into the early neurodevelopmental etiology of ASD.
Evaluation of the Diuretic Activities of 80% Methanol Leaf Extract and Solvent Fractions ofRumex nepalensisin Mice
Authors: Tafesse Fasika Argaw , Asrie Assefa Belay , Belete Tafere Mulaw 
Published: November 2023

AbstractBackgroundThe leaf ofRumex nepalensishas historically been employed to treat urinary retention and as a diuretic. Despite these assertions, there has been very little research addressing the diuretic effect of the leaves ofR. nepalensis. Therefore, this study was done to examine the diuretic properties of R. nepalensis leaves.MethodsCold maceration with 80% methanol was used to extract the coarsely powdered leaves ofR. nepalensis. The extract was separated using increasing polarity solvents, beginning with n-hexane, ethyl acetate, and water. Mice were split into sections to test the plant’s diuretic properties. The negative control groups were given either distilled water or 2% tween 80; the positive control groups were given furosemide (10 mg/kg); and the test groups were given the 80% methanol extract and solvent fractions orally at dosages of 100, 200, and 400 mg/kg. The urine volume was determined, and urine analysis was performed on each extract.ResultsAt dosage levels of 200 mg/kg and 400 mg/kg, the 80% methanol extract, ethyl acetate fraction, and aqueous fraction all produced substantial diuresis (p<0.001) as compared to the negative control. Similarly, mice given the 80% methanol extract, ethyl acetate fraction, and aqueous fraction demonstrated substantial natriuresis (p<0.001) and kaliuresis (p<0.001) at dosages of 200 mg/kg and 400 mg/kg, respectively, in comparison to the negative control.ConclusionThe diuretic activity ofR. nepalensiswas significantly seen in the 80% methanol extract, ethyl acetate, and aqueous fractions, which corroborated the plant’s traditional use.
Computational Design of Periplasmic Binding Protein Biosensors Guided by Molecular Dynamics
Authors: O’Shea Jack M. , Richardson Annis , Doerner Peter , Wood Christopher W. 
Published: November 2023

AbstractPeriplasmic binding proteins (PBPs) are bacterial proteins commonly used as scaffolds for substrate-detecting biosensors. In such biosensors, effector proteins, for example circularly permuted green fluorescent protein (cpGFP), are inserted into a PBP such that the effector protein’s output changes upon PBP-substate binding. The insertion site is often determined by comparison of PBPapo/holocrystal structures, but random insertion libraries have shown that this can miss the best sites. Here, we present a PBP biosensor design method based on residue contact analysis from molecular dynamics. This computational method identifies the best previously known insertion sites in the maltose binding PBP, and suggests further previously unknown sites. We experimentally characterise cpGFP insertions at these new sites, finding they too give functional biosensors. Our method is sufficiently flexible to both suggest insertion sites compatible with a variety of effector proteins and be applied to binding proteins beyond PBPs.
Oncogenic RAS drives rapid onset cellular plasticity and elicits a tumour-promoting neutrophil response at the inception of preneoplastic development
Authors: Elliot Abigail M. , Ribeiro Bravo Isabel , Astorga Johansson Jeanette , Hutton Esme , Cunningham Richard , Myllymäki Henna , Chang Kai Yee , Beltran Mariana , Dobie Ross , Elks Phil , Hansen Carsten Gram , Henderson Neil , Feng Yi 
Published: November 2023

AbstractTo date, very little is known regarding the earliest cellular and molecular events within the initial preneoplastic cell (PNC) niche that might determine the outcome of PNC development. Here, we combinein vivolive imaging and single cell transcriptomics to investigate the immediate cellular and molecular changes that occur in PNCs and responding innate immune cells within the first 24 hours following tumour initiation. We do so using an inducible transgenic zebrafish model of tumour initiation, in which oncogenic HRAS is conditionally expressed within the zebrafish epidermis. We found that, when expressed within basal keratinocytes, oncogenic HRAS was sufficient to drive several cancer hallmarks in nascent PNCs and their niche. Within 8 hours of oncogenic HRAS induction, basal keratinocytes began to dedifferentiate, followed by a bifurcation in PNC fate towards either a cellular state characterised by partial Epithelial-Mesenchymal-Transition (pEMT) and cancer stem cell features or a more differentiated cell state resembling suprabasal keratinocytes. By directly integrating data from PNCs and human SCC patients we show that both of these PNC states likely persist with established tumours, whilst the pEMT state corresponded with a more aggressive phenotype. Strikingly, markers of the PNC subpopulation that underwent pEMT correlated with poor prognosis in multiple human cancer types in the TCGA database. In addition, the pEMT PNC subpopulation expressed higher levels of cytokines that modulate neutrophil development and function, suggesting a major role for these cells in governing pro-tumour neutrophil responses. Indeed, we found that granulopoiesis was altered within PNC-bearing larvae, with a large proportion of neutrophils switching to an Arginase 2 positive phenotype that functioned to promote PNC proliferation. Similar to tumour associated neutrophils in the mammalian system, the cxcr1/2 – Il8 axis is involved in mediating the PNC-promoting function of neutrophils in our model. Thus, oncogenic RAS, when activated in the permissive cellular environment is sufficient to drive enabling cancer hallmarks, such as cellular plasticity and inflammation from the inception of the preneoplastic stage of cancer development. Furthermore, these same features may persist to drive malignant progression.
An Arabidopsis leaf expression atlas across diurnal and developmental scales
Authors: Vong Gina , McCarthy Kayla , Claydon Will , Davis Seth J. , Redmond Ethan J. , Ezer Daphne 
Published: November 2023

AbstractMature plant leaves are a composite of distinct cell types, including epidermal, mesophyll and vascular cells. Notably the proportion of these cells, and the relative transcript concentrations within different cell types may change over time. While gene expression data at a single-cell level can provide cell-type specific expression values, it is often too expensive to perform this on high resolution time series. Although bulk RNA-seq can be performed in a high resolution time series, the RNA-seq in whole leaves measures the average gene expression values across all cell types in each sample. In this study, we combined single cell RNA-seq data with time-series data from whole leaves to infer an atlas of cell type-specific gene expression changes over time forArabidopsis thaliana. We inferred how relative transcript concentrations of cell types vary across diurnal and developmental time scales. Importantly this analysis revealed three sub-groups of mesophyll cells that have distinct temporal profiles of expression. Finally, we develop tissue-specific gene networks that form a new community resource: An Arabidopsis Leaf Time-Dependent Atlas (AraLeTa), which allows users to extract gene networks that are confirmed by transcription factor binding data and specific to certain cell types, at certain times of day and certain developmental stages, which is available at:https://regulatorynet.shinyapps.io/araleta/.
Stable Equilibria under Random Fitness and Recombination Rates
Authors: Babel Noah 
Published: November 2023

AbstractWe develop and analyze a two-locus biallelic genetic model with randomized recombination rates and fitness matrices. While deterministic models reveal a trajectory toward the simplex center before stabilizing at polymorphisms, introducing random recombination pinpointed regions of attraction dependent on the fitness matrix and recombination fraction range. As recombination randomness intensifies, transitions in these attraction regions are observed. Analysis with random fitness matrices highlighted genotype attraction towards the tetrahedron vertices with edges guiding genotypic clustering.
Threat of water hyacinth (Eichhornia crassipes) on socio-economic and environmental sustainability of Koka and Ziway lakes, Ethiopia
Authors: Churko Esayas Elias , Nhamo Luxon , Chitakira Munyaradzi 
Published: November 2023

AbstractInvasive alien plant species cause severe socio-economic and environmental damage. In particular, the water hyacinth (Eichhornia crassipes) is an aggressive alien aquatic macrophyte that affects the socio-hydrologic and social environment in many parts of the globe. This study assessed the socio-economic and ecological impacts of the water hyacinth (WH) in Koka and Ziway Lakes in Ethiopia and recommends novel management practices. Purposive sampling design method was used to select households using systematic random sampling. The household sample size was determined with 95% confidence level. Data were collected through key informant interviews, focus group discussion and household surveys, prepared using the Kobo Toolbox which monitors data collectors online. A total of 413 households were sampled and the data were analysed through descriptive statistics and the ANOVA statistical package. At Lake Koka districts that the WH has caused 51% food insecurity by reducing food productivity, and 98.5% health distress through exposure to vector disease. At Lake Ziway districts it caused 81.6% food insecurity and 99.5% health distress. At both lakes, the WH affected the fishing industry by almost 100%. In terms of crop production, maize was significantly affected at Koka,ᵡ2(1, = 413) = 117.01, p<.001 and cabbage was significantly affected at Ziway,ᵡ2(1, N= 413) =6.36, p<.001. There was a statistically significant difference in annual income level, age of the household leader, and cost of recovery at household family size, F (9, 623.18) =14.38, p<.001; Wilk’s Λ=.632, partial η2=.14. Therefore, 195 (99.5%) households at Lake Koka and 215 (99.1%) at Lake Ziway illustrated the need for intervention to reduce health impacts and food insecurity. Despite the negative impact, at Lake Koka districts, 86.7% of the plant is used as cattle feed and 28.1% as fertilizer. At Lake Ziway, 42.9% of the plant is used as forage and 39.2%, as a fertilizer.
Automated classification of giant virus genomes using a random forest model built on trademark protein families
Authors: Ha Anh D. , Aylward Frank O. 
Published: November 2023

AbstractViruses of the phylumNucleocytoviricota, often referred to as “giant viruses,” are prevalent in various environments around the globe and play significant roles in shaping eukaryotic diversity and activities in global ecosystems. Given the extensive phylogenetic diversity within this viral group and the highly complex composition of their genomes, taxonomic classification of giant viruses, particularly incomplete metagenome-assembled genomes (MAGs) can present a considerable challenge. Here we developed TIGTOG (Taxonomic Information ofGiant viruses usingTrademarkOrthologousGroups), a machine learning-based approach to predict the taxonomic classification of novel giant virus MAGs based on profiles of protein family content. We applied a random forest algorithm to a training set of 1,531 quality-checked, phylogenetically diverseNucleocytoviricotagenomes using pre-selected sets of giant virus orthologous groups (GVOGs). The classification models were predictive of viral taxonomic assignments with a cross-validation accuracy of 99.6% to the order level and 97.3% to the family level. We found that no individual GVOGs or genome features significantly influenced the algorithm’s performance or the models’ predictions, indicating that classification predictions were based on a comprehensive genomic signature, which reduced the necessity of a fixed set of marker genes for taxonomic assigning purposes. Our classification models were validated with an independent test set of 823 giant virus genomes with varied genomic completeness and taxonomy and demonstrated an accuracy of 98.6% and 95.9% to the order and family level, respectively. Our results indicate that protein family profiles can be used to accurately classify large DNA viruses at different taxonomic levels and provide a fast and accurate method for the classification of giant viruses. This approach could easily be adapted to other viral groups.
Experimental design impacts the vector competence ofOrnithodorosticks for African swine fever virus: a meta-analysis of published evaluations
Authors: Bernard Jennifer , Madeira Sara , Otte Joachim , Boinas Fernando , Le Potier Marie-Frédérique , Vial Laurence , Jourdan-Pineau Hélène 
Published: November 2023

AbstractAfrican Swine Fever (ASF) is a highly economically devastating viral disease for swine. Soft ticks of the genusOrnithodorosare involved in its epidemiology, as vectors and natural reservoirs of African Swine Fever Virus (ASFV). The vector competence ofOrnithodorosticks for ASFV has been mainly studied by mimicking natural tick-to-pig transmission pathways through experimental infections in the laboratory. By reviewing the original research studies dating back to the 1960s on the vector competence ofOrnithodorosfor ASFV, we estimated the vector competence of 10 tick species in association with 38 viral strains resulting in 51 tick-virus associations. This assessment emphasized the extensive range of protocol designs employed and their impact on the success of tick infection with ASFV. Our results call for standardised procedures in vector competence experiments to facilitate further investigation and reduce potential experimental bias. In particular, we recommend the use of late nymphs or adult ticks from a laboratory colony to achieve efficient infection rates. In addition, viral inoculation should be carried out by blood meal rather than by injection, and preference should be given to high titre blood. Finally, detection of viral DNA should be performed 2 months after inoculation to distinguish between successful replication and residual virus in the tick.