bluuebunny/crossref_metadata_2025_split huggingface dataset:
HiTIPS: High-Throughput Image Processing Software for the Study of Nuclear Architecture and Gene Expression
Authors: Keikhosravi Adib , Almansour Faisal , Bohrer Christopher H. , Fursova Nadezda A. , Guin Krishnendu , Sood Varun , Misteli Tom , Larson Daniel R. , Pegoraro Gianluca 
Published: November 2023

AbstractHigh-throughput imaging (HTI) generates complex imaging datasets from a large number of experimental perturbations. Commercial HTI software for image analysis workflows does not allow full customization and adoption of new image processing algorithms in the analysis modules. While open-source HTI analysis platforms provide individual modules in the workflow, like nuclei segmentation, spot detection, or cell tracking, they are often limited in integrating novel analysis modules or algorithms. Here, we introduce the High-Throughput Image Processing Software (HiTIPS) to expand the range and customization of existing HTI analysis capabilities. HiTIPS incorporates advanced image processing and machine learning algorithms for automated cell and nuclei segmentation, spot signal detection, nucleus tracking, spot tracking, and quantification of spot signal intensity. Furthermore, HiTIPS features a graphical user interface that is open to integration of new algorithms for existing analysis pipelines and to adding new analysis pipelines through separate plugins. To demonstrate the utility of HiTIPS, we present three examples of image analysis workflows for high-throughput DNA FISH, immunofluorescence (IF), and live-cell imaging of transcription in single cells. Altogether, we demonstrate that HiTIPS is a user-friendly, flexible, and open-source HTI analysis platform for a variety of cell biology applications.
Three-dimensional chromatin landscapes in MLLr AML
Authors: Sui Pinpin , Zhang Peng , Pan Feng 
Published: November 2023

AbstractRearrangements of the mixed lineage leukemia (MLLr) gene are frequently associated with aggressive acute myeloid leukemia (AML). However, the treatment options are limited due to the genomic complexity and dynamics of 3D structure, which regulate oncogene transcription and leukemia development. Here, we carried out an integrative analysis of 3D genome structure, chromatin accessibility, and gene expression in gene-edited MLL-AF9 AML samples. Our data revealed profound MLLr-specific alterations of chromatin accessibility, A/B compartments, topologically associating domains (TAD), and chromatin loops in AML. The local 3D configuration of the AML genome was rewired specifically at loci associated with AML-specific gene expression. Together, our results show that the 3D chromatin undergoes extensive reorganization at multiple architectural levels, which underpins the remodeling of the transcriptome in MLLr AML.
Experimental evidence of nocturnal pollination services for berry crops
Authors: Blareau Elsa , Requier Fabrice 
Published: November 2023

AbstractInsect-mediated pollination is essential for crop production but is mainly studied considering diurnal pollinators only. Using pollinator exclusion techniques to prevent either diurnal or nocturnal insect visits we estimate the contribution of day-active and night-active pollinators to fruit set, seed set, fruit weight and fruit volume in three berry crops. We find that nocturnal pollination improves seed set compared to exclusion of all insect visits for one crop (raspberry), confirming the existence and importance of a nocturnal pollination service. Moreover, we found a general pattern where best crop pollination resulted from combined services of diurnal and nocturnal insect visits. These results call for urgent consideration of nocturnal pollination in crop production and management, towards inclusive pollinator-friendly schemes including night-active pollinators.
Auxetic patch material exhibits systolic thickening and restores pump function in a finite element model of acute myocardial infarction repair
Authors: Borrello Joseph , Zheng Zirui , Estrada Ana Cristina , Costa Kevin D. 
Published: November 2023

AbstractPassive mechanical reinforcement of the infarcted heart has been shown to counteract infarct expansion and left ventricular (LV) functional degradation. However, traditional patch plasty of the ischemic region also restricts diastolic filling, reducing cardiac output. These negative side-effects can be minimized with strategic modification of the standard patch, suggesting further functional improvements could be possible through a broader exploration of patch materials. This study examines the potential advantages of a patch graft with auxetic properties, having a negative Poisson’s ratio (ν < 0). For preliminary evaluation, an established finite element model of LV biomechanics pre- and post-acute infarction, originally developed for modeling patch plasty with non-auxetic, or meiotic, materials, was modified to simulate epicardial implantation of auxetic patch materials. A homogeneous auxetic patch graft (ν = -0.2) exhibited radial thickening during systole, driven by tension on the patch from the neighboring contracting myocardium; but the patch thickness expanded away from the LV cavity and therefore did not improve ventricular mechanics compared to a standard meiotic patch graft (ν = 0.4). Alternatively, a heterogeneous auxetic patch design with an outer reinforcement layer caused inwardly-directed systolic thickening that restored the LV pressure-volume relationship toward baseline function, without adversely affecting fiber stress in the border zone or remote myocardium compared to the meiotic patch. This computational modeling study demonstrates the potential to harness auxetic mechanical properties for improving LV pump function in the setting of acute myocardial infarction, motivating further experimental validation of auxetic metamaterial patch devices for surgical repair of injured myocardium.
TRAFICA: An Open Chromatin Language Model to Improve Transcription Factor Binding Affinity Prediction
Authors: Xu Yu , Wang Chonghao , Xu Ke , Ding Yi , Lyu Aiping , Zhang Lu 
Published: November 2023

AbstractIn silico transcription factor and DNA (TF-DNA) binding affinity prediction plays a vital role in examining TF binding preferences and understanding gene regulation. The existing tools employ TF-DNA binding profiles fromin vitrohigh-throughput technologies to predict TF-DNA binding affinity. However, TFs tend to bind to sequences in open chromatin regionsin vivo, such TF binding preference is seldomly considered by these existing tools. In this study, we developed TRAFICA, an open chromatin language model to predict TF-DNA binding affinity by integrating the characteristics of sequences from open chromatin regions in ATAC-seq experiments andin vitroTF-DNA binding profiles from high-throughput technologies. We applied self-supervised learning to pre-train TRAFICA on over 13 million nucleotide sequences from the peaks in ATAC-seq experiments to learn the TF binding preferencein vivo. TRAFICA was further fine-tuned using the TF-DNA binding profiles from PBM and HT-SELEX technologies to learn the association between TFs and their target DNA sequences. We observed that TRAFICA significantly outperformed both machine learning-based and deep learning-based tools in predictingin vitroandin vivoTF-DNA binding affinity. These findings indicate that considering the characteristics of sequences from open chromatin regions could significantly improve TF-DNA binding affinity prediction, particularly when limited TF-DNA binding profiles from high-throughput technologies are available for specific TFs.
Electrophysiological analyses of human dorsal root ganglia and human induced pluripotent stem cell-derived sensory neurons from male and female donors
Authors: Zurek Nesia A. , Ehsanian Reza , Goins Aleyah E. , Adams Ian M. , Petersen Timothy , Goyal Sachin , Shilling Mark , Westlund Karin N. , Alles Sascha R.A. 
Published: November 2023

AbstractHuman induced pluripotent stem cell-derived sensory neurons (hiPSC-SNs) and human dorsal root ganglia (hDRG) neurons are popular tools in the field of pain research; however, few groups make use of both approaches. For screening and analgesic validation purposes, important characterizations can be determined of the similarities and differences between hDRG and hiPSC-SNs. This study focuses specifically on electrophysiology properties of hDRG in comparison to hiPSC-SNs. We also compared hDRG and hiPSC-SNs from both male and female donors to evaluate potential sex differences. We recorded neuronal size, rheobase, resting membrane potential, input resistance, and action potential waveform properties from 83 hiPSCs-SNs (2 donors) and 108 hDRG neurons (9 donors). We observed several statistically significant electrophysiological differences between hDRG and hiPSC-SNs, such as size, rheobase, input resistance, and several actional potential (AP) waveform properties. Correlation analysis also revealed many properties that were positively or negatively correlated, some of which were differentially correlated between hDRG and hiPSC-SNs. This study shows several differences between hDRG and hiPSC-SNs and allows better understanding of the advantages and disadvantages of both for use in pain research. We hope this study will be a valuable resource for pain researchers considering the use of these humanin vitrosystems for mechanistic studies and/or drug development projects.
Limitations of line-scan MRI for directly measuring neural activity
Authors: Wilson Joshua M. , Wu Hua , Kerr Adam B. , Wandell Brian A. , Gardner Justin L. 
Published: November 2023

AbstractSeveral groups have reported using 2D line-scan MRI sequences in humans and mice to directly measure neural responses to stimuli (the “DIANA response”). Other groups have been unable to replicate the DIANA response, even with higher field strength and more repetitions. Part of this discrepancy is likely due to a limited understanding of the noise profile of the line-scan MRI sequence: specifically, the consequences of deviations from the assumption of stationarity between each line acquisition. Here, we collected data using an MRI line-scan method while human subjects viewed a blank screen with the purpose of studying noise unique to the acquisition sequence. We found temporal fluctuations in the reconstructed time series from localized groups of voxels that could easily be confused with neural responses to stimuli. These fluctuations were present both in the head and in the surrounding empty volume along the span of the phase-encoding direction from the head. The timing of these fluctuations varied systematically and smoothly along the phase-encoding direction. These features can be explained by a model that accounts for the acquisition sequence and incorporates time-varying contrast fluctuations in the imaging substrate. Using the model, we quantify the amount of cortical- and scan-averaging one might need to reliably distinguish a DIANA response from noise.
PAH DEFICIENT PATHOLOGY IN HUMANIZED c.1066-11G>A PHENYLKETONURIA MICE
Authors: Martínez-Pizarro Ainhoa , Picó Sara , López-Márquez Arístides , Rodriguez-López Claudia , Montalvo Elena , Alvarez Mar , Castro Margarita , Ramón-Maiques Santiago , Pérez Belén , Lucas José J , Richard Eva , Desviat Lourdes R 
Published: November 2023

AbstractWe have generated using CRISPR/Cas9 technology a partially humanized mouse model of the neurometabolic disease phenylketonuria (PKU), carrying the highly prevalentPAHvariant c.1066-11G>A. This variant creates an alternative 3’ splice site, leading to the inclusion of 9 nucleotides coding for 3 extra amino acids between Q355 and Y356 of the protein. HomozygousPahc.1066-11A mice, with a partially humanized intron 10 sequence with the variant, accurately recapitulate the splicing defect and present almost undetectable hepatic PAH activity. They exhibit fur hypopigmentation, lower brain and body weight and reduced survival. Blood and brain phenylalanine levels are elevated, along with decreased tyrosine, tryptophan and monoamine neurotransmitter levels. They present behavioral deficits, mainly hypoactivity and diminished social interaction, locomotor deficiencies and an abnormal hind-limb clasping reflex. Changes in the morphology of glial cells, increased GFAP and Iba1 staining signals and decreased myelinization are observed. Hepatic tissue exhibits nearly absent PAH protein, reduced levels of chaperones DNAJC12 and HSP70 and increased autophagy markers LAMP1 and LC3BII, suggesting possible coaggregation of mutant PAH with chaperones and subsequent autophagy processing. This PKU mouse model with a prevalent human variant represents a useful tool for pathophysiology research and for novel therapies development.
Pseudomonas syringaeinfectivity correlates to altered transcript and metabolite levels ofArabidopsisMediator mutants
Authors: Blomberg Jeanette , Tasselius Viktor , Vergara Alexander , Karamat Fazeelat , Imran Qari Muhammad , Strand Åsa , Rosvall Martin , Björklund Stefan 
Published: November 2023

ABSTRACTRapid metabolic responses to pathogens are essential for plant survival and depend on numerous transcription factors. Mediator is the major transcriptional co-regulator for integration and transmission of signals from transcriptional regulators to RNA polymerase II. Using four Arabidopsis Mediator mutants,med16,med18,med25andcdk8, we studied how differences in regulation of their transcript and metabolite levels correlate to their responses toPseudomonas syringaeinfection. We found thatmed16andcdk8were susceptible, whilemed25showed increased resistance. Glucosinolate, phytoalexin and carbohydrate levels were reduced already before infection inmed16andcdk8, but increased inmed25, which also displayed increased benzenoids levels. Early after infection, wild type plants showed reduced glucosinolate and nucleoside levels, but increases in amino acids, benzenoids, oxylipins and the phytoalexin Camalexin. The Mediator mutants showed altered levels of these metabolites and in regulation of genes encoding key enzymes for their metabolism. At later stage, mutants displayed defective levels of specific amino acids, carbohydrates, lipids and jasmonates which correlated to their infection response phenotypes. Our results reveal thatMED16,MED25andCDK8are required for a proper, coordinated transcriptional response of genes which encode enzymes involved in important metabolic pathways for Arabidopsis responses toPseudomonas syringaeinfections.HIGHLIGHTPlants need to defend themselves against different types of infections. We show that subunits of the Mediator transcriptional coactivator coordinate metabolic responses ofArabidopsis thalianato infections byPseudomonas syringae.
Chromosome-scale genome assembly ofPoa trivialisand population genomics reveals widespread gene flow in a cool-season grass seed production system
Authors: Brunharo Caio A. C. G. , Benson Christopher W. , Huff David R. , Lasky Jesse R. 
Published: November 2023

AbstractPoa trivialis(L.) is a cool-season grass species found in various environments worldwide. In addition to being a desired turfgrass species, it is a common weed of agricultural systems and natural areas. As a weed, it is an important contaminant of commercial cool-season grass seed lots, resulting in widespread gene flow facilitated by human activities and causing significant economic losses to farmers. To better understand and manage infestations, we assembled and annotated a haploid genome ofP. trivialisand studied troublesome field populations from Oregon, the largest cool-season grass seed producing region in the United States. The genome assembly resulted in 1.35 Gb of DNA sequence distributed among seven chromosome-scale scaffolds, revealing a high content of transposable elements, conserved synteny withP. annua, and a close relationship with other C3grasses. A reduced-representation sequencing analysis of field populations revealed limited genetic diversity and suggested potential gene flow and human-assisted dispersal in the region. The genetic resources and insights intoP. trivialisprovided by this study will improve weed management strategies and enable the development of molecular detection tests for contaminated seed lots to limit seed-mediated gene flow. These resources should also be beneficial for turfgrass breeders seeking to improve desirable traits of commercialP. trivialisvarieties and help to guide breeding efforts in other crops to enhance the resiliency of agricultural ecosystems under climate change.Significance statementThe chromosome-scale assembly ofPoa trivialisand population genomic analyses provide crucial insights into the gene flow of weedy populations and contribute a valuable genomic resource for the plant science community.
Traitor-virus-guided discovery of novel antiviral factors
Authors: Prelli Bozzo Caterina , Laliberté Alexandre , De Luna Aurora , Pastorio Chiara , Regensburger Kerstin , Krebs Stefan , Graf Alexander , Blum Helmut , Volcic Meta , Sparrer Konstantin M.J. , Kirchhoff Frank 
Published: November 2023

AbstractComplex pathogen-host interactions govern the outcome of viral exposures but remain poorly understood because current methods to elucidate antiviral mechanisms are prone to artefacts and lack sensitivity. Here, we developed a virus-guided technology platform where the pathogen itself reveals its cellular opponents. To accomplish this, we engineered replication-competent HIV-1 expressing sgRNAs targeting potential antiviral genes in Cas9-expressing CD4+T cells. Simultaneous analysis of HIV-1 constructs targeting >500 candidate genes revealed that sgRNAs againstGRN,CIITA,EHMT2,CEACAM3,CC2D1B,RHOAandHMOX1are strongly enriched over several rounds of replication. Overexpression and knock-out studies confirmed the antiretroviral activity of most factors but failed for some. Finally, we show that lack of the accessorynefgene increased enrichment of sgRNAs targeting SERINC5 and IFI16 demonstrating that this method allows identification of targets of accessory proteins. The versatile and effective HIV-guided CRISPR technology offers numerous possibilities for clarification of virus-host interactions and innate defense mechanisms.
Flood-irrigated agriculture mediates climate-induced wetland scarcity for summering sandhill cranes in western North America
Authors: Donnelly J. Patrick , Collins Daniel P. , Knetter Jeffrey M. , Gammonley James H. , Boggie Matthew A. , Grisham Blake A. , Cathy Nowak M. , Naugle David E. 
Published: November 2023

ABSTRACTDocumenting a species’ extent is often the first step in understanding its ecology and is critical to informing conservation planning. Basic information about species distributions is lacking in many regions of the world, forcing natural resource managers to answer complex ecological questions with incomplete data. Information gaps are compounded by climate change, driving resource bottlenecks that can act as new and powerful demographic constraints on fauna. Here, we reconstructed greater sandhill crane (Antigone canadensis tabida) summering range in western North America using movement data from 120 GPS-tagged individuals to determine how landscape composition shaped their distributions. Landscape variables developed from remotely sensed data were combined with bird locations using cloud computing and machine learning to model distribution probabilities. Additionally, land-use practices and land ownership were summarized within summer range as a measure of use dependence. Wetland variables identified as important predictors of bird distributions were also evaluated in a post hoc analysis using satellite imagery to measure the long-term (1984–2022) effects of climate-driven surface water drying. Wetlands and associated agricultural practices accounted for 1.2% of the summer range but were key predictors of greater sandhill crane occurrence. Bird distributions were patterned primarily by riparian floodplains that concentrated water, wetlands, and flood-irrigated agriculture in otherwise arid and semi-arid landscapes. Findings highlighted the critical role of private lands in greater sandhill crane ecology as they accounted for 78% of predicted distributions. Wetland drying observed in portions of the range from 1984 to 2022 represented an emerging ecological bottleneck that could limit future greater sandhill crane summer range. Study outcomes provide novel insight into the significance of ecosystem services provided by flood-irrigated agriculture that supported nearly 60% of the wetland resources used by birds. Findings suggest greater sandhill cranes function as an umbrella species for agroecology and climate change adaptation strategies seeking to reduce agricultural water use through improved efficiency while also maintaining distinct flood-irrigation practices supporting greater sandhill cranes and other wetland-dependent wildlife. To inform conservation design, we make our wetland and sandhill crane summering distributions publicly available as interactiveweb-basedmapping tools.
Habitat remediation followed by managed connectivity reduces unwanted changes in evolutionary trajectory of high extirpation risk populations
Authors: Lamka Gina F. , Willoughby Janna R. 
Published: November 2023

ABSTRACTAs we continue to convert green spaces into roadways and buildings, connectivity between populations and biodiversity will continue to decline. In threatened and endangered species, this trend is particularly concerning because the cessation of immigration can cause increased inbreeding and loss of genetic diversity, leading to lower adaptability and higher extirpation probabilities in these populations. Unfortunately, monitoring changes in genetic diversity from management actions such as assisted migration and predicting the extent of introduced genetic variation that is needed to prevent extirpation is difficult and costly in situ. Therefore, we designed an agent-based model to link population-wide genetic variability and the influx of unique alleles via immigration to population stability and extirpation outcomes. These models showed that management of connectivity can be critical in restoring at-risk populations and reducing the effects of inbreeding depression; increased connectivity prevented extirpation for the majority of scenarios we considered (71.5% of critically endangered populations and 100% of endangered and vulnerable populations). However, the rescued populations were more similar to the migrant source population (average FSTrange 0.05 – 0.10) compared to the historical recipient population (average FSTrange 0.23 – 0.37). This means that these management actions not only recovered the populations from the effects of inbreeding depression, but they did so in a way that changed the evolutionary trajectory that was predicted and expected for these populations prior to the population crash. This change was most extreme in populations with the smallest population sizes, which are representative of critically endangered species that could reasonably be considered candidates for restored connectivity or translocation strategies. Understanding how these at-risk populations change in response to varying management interventions has broad implications for the long-term adaptability of these populations and can improve future efforts for protecting locally adapted allele complexes when connectivity is restored.