bluuebunny/crossref_metadata_2025_split huggingface dataset:
scHiCcompare: an R package for differential analysis of single-cell Hi-C data
Authors: Nguyen My , Wall Brydon P. G. , Harrell J. Chuck , Dozmorov Mikhail G. 
Published: November 2024

AbstractChanges in the three-dimensional (3D) structure of the human genome are key indicators of cancer and developmental disorders. Techniques like chromatin conformation capture (Hi-C) have been developed to study these global 3D structures, typically requiring millions of cells and an extremely high sequencing depth (around 1 billion reads per sample) for bulk Hi-C. In contrast, single-cell Hi-C (scHi-C) captures 3D structures at the individual cell level but faces significant data sparsity, marked by a high proportion of zeros. While differential analysis methods exist for bulk Hi-C data, they are limited for scHi-C data. To address this, we developed a method for differential scHi-C analysis, building on existing techniques in the HiCcompare R package. Our approach imputes sparse scHi-C data by considering genomic distances and creates pseudo-bulk Hi-C matrices by summing condition-specific data. The data are normalized using LOESS regression, and differential chromatin interactions are detected via Gaussian Mixture Model (GMM) clustering. Our workflow outperforms existing methods in identifying differential chromatin interactions across various genomic distances, fold changes, resolutions, and sample sizes in both simulated and experimental contexts. This allows for effective detection of cell type-specific differences in chromatin structure, which has meaningful associations with biological and epigenetic features. Our method is implemented in the scHiCcompare R package, available athttps://github.com/dozmorovlab/scHiCcompare.Graphical abstract
Ultrastructural expansion microscopy (U-ExM) visualization of malaria parasite dense granules using RESA as a representative marker protein
Authors: Fukumoto Junpei , Tsuboi Takafumi , Takashima Eizo 
Published: November 2024

AbstractDense granules (DG) are understudied apical organelles in merozoites, the malaria parasite stage that invades erythrocytes. Only six proteins have been identified which localize to DGs, despite that DG proteins play crucial roles in multiple steps of intraerythrocytic parasite development. To develop a tool for investigating DG structure and function, this study applied ultrastructural expansion microscopy (U-ExM) to visualize the ring-infected erythrocyte surface antigen (RESA) inPlasmodium falciparummerozoites. Merozoites were expanded to approximately four times their original size, allowing the identification of DGs without the need for electron microscopy. RESA localization in merozoite DGs was confirmed by staining with a combination of anti-RESA mAb and protein staining by NHS-ester. The translocation of RESA to the infected erythrocyte membrane was also observed in early ring-stage parasites. These results are in good agreement with the RESA localization reported using immunoelectron microscopy (IEM). By using U-ExM, the identification of novel DG proteins will be facilitated without time-consuming IEM, thereby contributing to describing erythrocyte parasitism byP. falciparum.
Image-based DNA Sequencing Encoding for Detecting Low-Mosaicism Somatic Mobile Element Insertions
Authors: Tan Miaomiao , Lin Zhinan , Chen Zhuofu , Park Junseok , He Ziting , Zhou Haonan , Lee Eunjung A. , Gao Zhipeng , Zhu Xiaowei 
Published: November 2024

AbstractActive LINE-1 (L1),Alu, and SVA mobile elements in the human genome are capable of retrotransposition, resulting in novel mobile element insertions (MEIs) in both germline and somatic tissues. Detecting MEIs through DNA sequencing relies on supporting reads overlapping MEI junctions; however, artifacts from DNA amplification, sequencing, and alignment errors produce numerous false positives. Systematic detection of somatic MEIs, particularly those with low mosaicism, remains a significant challenge. Previous methods had required a high number of supporting reads which limits the detection sensitivity, or human inspections that are susceptible to biases. Here, we developed RetroNet, an algorithm that encodes MEI-supporting sequencing reads into images, and employs a deep neural network to identify somatic MEIs with as few as two reads. Trained on extensive and diverse datasets and benchmarked across various conditions, RetroNet surpasses previous methods and eliminates the need for extensive manual examinations. When applied to bulk whole genome sequencing of a cancer cell line, RetroNet achieved an average precision of 0.885 and recall of 0.845 for detecting somatic L1 insertions, including four true mutations with only two supporting reads. RetroNet is applicable to the rapidly generated short-read sequencing data and has the potential to provide further insights into the functional and pathological implications of somatic retrotranspositions.
Understanding How Biopolymers Found in Marine Ecosystems Impact the Efficacy of Bacteriophages against Bacteria
Authors: Rupareliya Rhea , Kwack Joyce , Quan Dylan , Kim Tay 
Published: November 2024

AbstractBacteriophages are abundant in Earth’s ecosystem and serve as valuable mediators in marine environments, regulating bacterial populations in oceans, hot springs, and salterns, among others. However, bacteriophages have high-specificity to their host, thus making it difficult to study bacteria-phage relationships. In this study, we observe whether naturally occurring biopolymers (coral mucin (from Stylophora pistillata), chitin, and sodium alginate) increase bacteriophage affinity to bacteria by recording the plaques formed throughout 15-minute time intervals. We use an isolatedE. colistrain and its corresponding T7 phage, as well as isolated bacteria and phage strains from a coral sample (labeled Stylophora pistillata or “Coral 1”). The research conducted plaque assays using minimal media solution to quantify phage-forming units (PFUs) using 2 bacterial forms, Coral 1 and E. coli and Mucin, Sodium Alginate, and Chitin as biopolymers. Our research found that the biopolymers had an effective impact on the generation of PFUs in our bacterial cultures for all samples. While we were unable to conduct future plaque assays, the information we have now is important to discovering ways to increase phage efficiency in marine environments to help maintain nutrient resource levels in such ecosystems.
Elucidating the Mechanism Underlying UBA7•UBE2L6 Disulfide Complex Formation
Authors: Chen Pei-Tzu , Yeh Jia-Yin , Weng Jui-Hsia , Wu Kuen-Phon 
Published: November 2024

AbstractWe elucidate cryo-EM structure and formation of the ubiquitin-associated bovine UBA7•UBE2L6 disulfide complex, shedding light on a highly specific and evolutionarily conserved mechanism governing ISG15 conjugation, a pivotal process in the immune response. UBA7 displays a unique capacity to recognize UBE2L6, distinct from this latter’s homolog UBE2L3, highlighting the intricacies of cellular regulation. Inter-species interactions of the resulting complex further underscore its significance. We characterize three crucial factors that influence UBA7•UBE2L6 disulfide complex formation: (1) strong binding affinity and specificity; (2) conformational differences in the catalytic cysteine capping loop (CCL); and (3) increased thiolate/thiol ratios at catalytic cysteines. Modification of any of these factors profoundly impacts complex activation and the ISG15 transfer cascade. This redox-sensitive complex implies a link between oxidative stress and regulation of the immune response, highlighting a potential therapeutic target for modulating immune reactions arising from infections and inflammatory conditions.
Stalling of the endometrial decidual reaction determines the recurrence risk of miscarriage
Authors: Muter Joanne , Kong Chow-Seng , Nebot Mireia Taus , Tryfonos Maria , Vrljicak Pavle , Brighton Paul J. , Dimakou Danai B. , Vickers Megan , Yoshihara Hiroyuki , Ott Sascha , Tan Bee K. , Bennett Phillip R. , Quenby Siobhan , Richter Alex , Van de Velde Hilde , Lucas Emma S. , Rawlings Thomas M. , Brosens Jan J. 
Published: November 2024

ABSTRACTIn each menstrual cycle, progesterone acting on estrogen-primed endometrium elicits an inflammatory decidual reaction, rendering it poised for embryo implantation and transformation into the decidua of pregnancy. Here, we show that the sequential functions of the decidual reaction - implantation and decidualization - pivot on the time-sensitive loss of progesterone-resistant stromal cells that form a transient implantation niche and reciprocal expansion of progesterone-responsive pre-decidual cells. In parallel, proliferation and differentiation increase the abundance of immunotolerant uterine natural killer (uNK) cells. Examination of pre-pregnancy endometrial biopsies from 924 women revealed that the frequency of cycles culminating in a blunted or stalled decidual reaction closely aligns with the age-independent recurrence risk of miscarriage. Further, analysis of 632 biopsies obtained in different cycles from 316 women indicated that prior miscarriages disrupt intercycle endometrial homeostasis, an observation supported by modelling the impacts of prolonged decidual inflammation in three-dimensional endometrial assembloids. Although stalling of the decidual reaction is often accompanied by a poor expansion of immunotolerant uNK cells, miscarriages do not impact intercycle uNK cell dynamics. Our findings indicate that intrinsic uterine mechanisms hardwire the recurrence risk of miscarriage, underscoring the need for pre-pregnancy diagnostics and therapeutics.One Sentence SummaryThe frequency of menstrual cycles culminating in a suboptimal decidual reaction determines the recurrence risk of miscarriage.
SARS-CoV-2 infection enhancement by Amphotericin B: Implications for disease management
Authors: Nguyen Dung , Laidlaw Stephen M. , Dong Xiaofeng , Wand Matthew , Horton Amanda , Sutton Mark , Tree Julia , Milligan Rachel , Erdmann Maximilian , Matthews David , Davidson Andrew D. , Rahman Khondaker Miraz , Hiscox Julian A. , Carroll Miles 
Published: November 2024

AbstractSevere coronavirus disease 2019 (COVID-19) patients who require hospitalisation are at high risk of invasive pulmonary mucormycosis. Amphotericin B (AmB), which is the first line therapy for invasive pulmonary mucormycosis, has been shown to promote or inhibit replication of a spectrum of viruses. In this study, we first predicted that AmB and Nystatin had strong interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins using in silico screening, indicative of drugs with potential therapeutic activity against this virus. Subsequently, we investigated the impact of AmB, Nystatin, Natamycin, Fluconazole and Caspofungin on SARS-CoV-2 infection and replicationin vitro. Results showed that AmB and Nystatin actually increased SARS-CoV-2 replication in Vero E6, Calu-3 and Huh7 cells. At optimal concentrations, AmB and Nystatin increase SARS-CoV-2 replication by up to 100-and 10-fold in Vero E6 and Calu-3 cells, respectively. The other antifungals tested had no impact on SARS-CoV-2 infectionin vitro. Drug kinetic studies indicate that AmB enhances SARS-CoV-2 infection by promoting viral entry into cells. Additionally, knockdown of genes encoding for interferon-induced transmembrane (IFITM) proteins 1, 2, and 3 suggests AmB enhances SARS-CoV-2 cell entry by overcoming the antiviral effect of the IFITM3 protein. This study further elucidates the role of IFITM3 in viral entry and highlights the potential dangers of treating COVID-19 patients, with invasive pulmonary mucormycosis, using AmB.ImportanceAmB and Nystatin are common treatments for fungal infections but were predicted to strongly interact with SARS-CoV-2 proteins, indicating their potential modulation or inhibition against the virus. However, our tests revealed that these antifungals, in fact, enhance SARS-CoV-2 infection by facilitating viral entry into cells. The magnitude of enhancement could be up to 10-or 100-fold depending on cell lines used. These findings indicate that AmB and Nystatin have the potential to enhance disease when given to patients infected with SARS-CoV-2 and therefore should not be used for treatment of fungal infections in active COVID-19 cases.
Dystrophininteracts withMsp300to Regulate Myonuclear Positioning and Microtubule Organization
Authors: Padilla Jorel R. , Qiu Yunshu , Aleck Grace , Ferreria Lillie , Wu Sharon , Gibbons William , Mandigo Torrey , Folker Eric S. 
Published: November 2024

AbstractDuringDrosophilamyognesis, myonuclei are actively moved during embryogenesis, and their spacing is maintained through an anchoring mechanism in the fully differentiated myofiber. While we have identified microtubule associated proteins, motors, and nuclear envelope proteins that regulate myonuclear spacing, the developmental time during which each gene functions has not been tested. Here we have identified aDystrophinas required only for the maintenance of myonuclear spacing. Furthermore, we demonstrate thatDystrophingenetically interacts with the KASH-domain proteinMsp300to maintain myonuclear spacing. Mechanistically, bothDystrophinandMsp300regulate microtubule organization. Specifically, in animals with disrupted expression of bothDystrophinandMsp300, microtubule colocalization with sarcomeres is reduced. Taken altogether, these data indicate that the peripheral membrane protein Dystrophin, and the outer nuclear membrane protein Msp300, together regulate the organization of the microtubule network which then acts as an anchor to restrict myonuclear movement in contractile myofibers. These data are consistent with growing evidence that myonuclear movement and myonuclear spacing are critical to muscle development, muscle function, and muscle repair and provide a mechanism to connect disparate muscle diseases.Summary StatementHere we show thatDystrophinis required to maintain the spacing of nuclei in differentiated myofibers. Furthermore,Dystrophinachieves this function via a genetic interaction withMsp300which regulates microtubule organization.
From aerial drone to QTL: Leveraging next-generation phenotyping to reveal the genetics of color and height in field-grownLactuca sativa
Authors: Dijkhuizen Rens , van Eijnatten Abraham L. , Mehrem Sarah L. , van den Bergh Esther , van Lieshout Jelmer , Spaninks Kiki , Kaandorp Steven , Offringa Remko , Proveniers Marcel , van den Ackerveken Guido , Snoek Basten L. 
Published: November 2024

AbstractIn recent years, the automation of genotyping has significantly enhanced the efficiency of genome-wide association studies. As a result, phenotyping rather than genotyping is now the rate-limiting step, especially in field experiments. For this reason, there is a strong need to further automate in-field phenotyping. Here we present a GWAS study on 194 field-grown accessions of lettuce (Lactuca sativa). These accessions were non-destructively phenotyped at two time points 15 days apart using an unmanned aerial vehicle. Our high throughput phenotyping approach integrates an RGB camera, a multispectral camera to measure the reflectance at 5 wavelengths (blue, green, red, red edge, near-infrared), and precise height estimation. We used the mean and other descriptives such as median, quantiles, minimum and maximum to quantify different aspects of color and height variation in lettuce from the drone images. Using this approach, we confirm several previously described QTLs, now in populations grown under field conditions, and identify several new QTLs for plant-height and color.
Alterations and Imbalance of Dorsal and Ventral Mossy Cells in a Mouse Model of Epilepsy
Authors: Huang Christine S. , Houser Carolyn R. 
Published: November 2024

AbstractMossy cells (MCs) in the hilus of the dentate gyrus (DG) are important for regulating activity of dentate granule cells and are particularly vulnerable to excitotoxic damage in epilepsy. Recent studies have demonstrated that MCs in the dorsal and ventral DG differ in the patterns of their axonal projections and neurochemical identities. Such differences raised questions about the vulnerability and plasticity of dorsal and ventral MCs in epilepsy and led to this study using a mouse pilocarpine model of epilepsy. Dorsal MCs were labeled by transfection of Cre-dependent eYFP in the dorsal DG ofCalcrl-Cremice that express Cre selectively in MCs. Ventral MCs were labeled with calretinin (CR), which labels ventral but not dorsal MCs. At 6-8 weeks after pilocarpine treatment, MC loss and axonal projections of remaining MCs were studied in control and pilocarpine-treated mice with confocal microscopy. Dorsal MCs were severely depleted, but many ventral MCs remained, and quantitative analysis of GluA2-labeled hilar neurons demonstrated a proportionally greater loss of dorsal MCs (77.6% loss) than ventral MCs (21.5% loss). Loss of dorsal MCs led to a marked reduction in the dorsal commissural pathway, while the remaining ventral MCs maintained a prominent, though reduced, ventral to dorsal association pathway. In pilocarpine-treated animals, a plexus of CR-labeled fibers extended into the middle molecular layer, suggesting axonal sprouting of remaining ventral MCs, with some of these fibers in contact with parvalbumin-labeled dendrites. These findings suggest that dorsal and ventral MCs differ in their vulnerability to seizure-induced damage in this animal model, creating an imbalance between the dorsal and ventral MC pathways that could alter the excitatory/inhibitory balance within the dentate gyrus.
Organ structure and bacterial microbiogeography in a reproductive organ of the Hawaiian bobtail squid reveal dimensions of a defensive symbiosis
Authors: Kamp Derrick L. , Kerwin Allison H. , McAnulty Sarah J. , Nyholm Spencer V. 
Published: November 2024

ABSTRACTMany plants and animals house symbiotic microorganisms in specialized tissues or organs. Here, we used multidimensionalin-situimaging techniques to illuminate how host organ structure and bacterial microbiogeography contribute to the symbiotic function of an organ in the Hawaiian bobtail squid,Euprymna scolopes. Along with the well-studied light organ, femaleE. scolopesharbor a community of bacteria in the accessory nidamental gland (ANG). The ANG is a dense network of epithelium-lined tubules, some of which are dominated by a single bacterial taxon. These bacteria are deposited into squid eggs, where they defend the developing embryos from harmful biofouling. This study used a combination of imaging techniques to visualize different dimensions of the ANG and its bacterial communities. Imaging entire organs with light sheet microscopy revealed that the ANG is a composite tissue of individual, non-intersecting tubules that each harbor their own bacterial population. The organ is bisected, with tubules converging towards two points in the organ. At these points, tubules empty in a space where bacteria can mix with squid jelly to be deposited onto eggs. Observations of bacterial populations correlated bacterial taxa with cell morphology and show that tubule populations varied: some contained populations of mixed phyla while some tubules contained only one genus of bacteria. Together, these data shed light on how bacterial populations interact within the ANG and how the host uses physical structure to maintain and employ a symbiotic bacterial population in a defensive context.IMPORTANCESequence-based microbiome studies have revealed much about how hosts interact with communities of symbiotic microbiota, but often lack a spatial understanding of how microbes relate with each other and the host in which they reside. This study used a combination of microscopy techniques to reveal how the structure of a symbiotic organ in the female bobtail squid,Euprymna scolopeshouses diverse, beneficial bacterial populations and deploys them for egg defense. These findings suggest that spatial partitioning may be key to harboring a diverse population of antimicrobial-producing bacteria and establish a foundation for further understanding how host structures mediate symbiotic interactions.
Development of the Left Arcuate Fasciculus is Linked to Learning Gains in Reading, but not Math
Authors: Roy Ethan , Harriott Emily M. , Nguyen Tin Q. , Richie-Halford Adam , Rokem Ariel , Cutting Laurie E. , Yeatman Jason D. 
Published: November 2024

AbstractPast studies leveraging cross-sectional data have raised questions surrounding the relationship between diffusion properties of the white matter and academic skills. Some studies have suggested that white matter properties serve as static predictors of academic skills, whereas other studies have observed no such relationship. On the other hand, longitudinal studies have suggested that within-individual changes in the white matter are linked to learning gains over time. In the present study, we look to replicate and extend the previous longitudinal results linking longitudinal changes in the white matter properties of the left arcuate fasciculus to individual differences in reading development. To do so, we analyzed diffusion MRI data, along with reading and mathematics scores in a longitudinal sample of 340 students as they progressed from 1st grade into 4th grade. Longitudinal growth models revealed that year-to-year within-individual changes in reading scores, but not math, were related to the development of the left arcuate fasciculus. These findings provide further evidence linking the dynamics of white matter development and learning in a unique sample and highlight the importance of longitudinal designs.
Systematic review and meta-analysis of bulk RNAseq studies in human Alzheimer’s disease brain tissue
Authors: Heberle Bernardo Aguzzoli , Fox Kristin L. , Libermann Lucas Lobraico , Xavier Sophia Ronchetti Martins , Dallarosa Guilherme Tarnowski , Santos Rhaná Carolina , Fardo David W. , Viola Thiago Wendt , Ebbert Mark T. W. 
Published: November 2024

AbstractObjectiveTo systematically review and meta-analyze bulk RNA sequencing studies comparing Alzheimer’s disease (AD) patients with controls in human brain tissue, assessing study quality and identifying key genes and pathways.MethodsWe searched PubMed, Web of Science, and Scopus on September 23, 2023, for studies using bulk RNAseq on primary human brain tissue from AD patients and controls. Excluded were non-primary tissue, re-analyses without new data, limited RNA types and gene panels. Quality was assessed with a 10-category tool. Meta-analysis used high-quality datasets.ResultsFrom 3,266 records, 24 studies met criteria. Meta-analysis found 571 differentially expressed genes (DEGs) in temporal lobe and 189 in frontal lobe; overlapping pathways included "Tube morphogenesis" and "Neuroactive ligand-receptor interaction."LimitationsStudy heterogeneity and limited data tables constrained the review.ConclusionsRigorous methods are vital in AD transcriptomic studies. Findings enhance understanding of transcriptomic changes, aiding biomarker and therapeutic development.RegistrationPROSPERO (CRD42023466522).