bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generalizable links between symptoms of borderline personality disorder and functional connectivity
Authors: Shafiei Golia , Keller Arielle S. , Bertolero Maxwell , Shanmugan Sheila , Bassett Dani S. , Chen Andrew A. , Covitz Sydney , Houghton Audrey , Luo Audrey , Mehta Kahini , Salo Taylor , Shinohara Russell T. , Fair Damien , Hallquist Michael N. , Satterthwaite Theodore D. 
Published: August 2023

ABSTRACTBackgroundSymptoms of borderline personality disorder (BPD) often manifest in adolescence, yet the underlying relationship between these debilitating symptoms and the development of functional brain networks is not well understood. Here we aimed to investigate how multivariate patterns of functional connectivity are associated with symptoms of BPD in a large sample of young adults and adolescents.MethodsWe used high-quality functional Magnetic Resonance Imaging (fMRI) data from young adults from the Human Connectome Project: Young Adults (HCP-YA;N= 870, ages 22-37 years, 457 female) and youth from the Human Connectome Project: Development (HCP-D;N= 223, age range 16-21 years, 121 female). A previously validated BPD proxy score was derived from the NEO Five Factor Inventory (NEO-FFI). A ridge regression model with 10-fold cross-validation and nested hyperparameter tuning was trained and tested in HCP-YA to predict BPD scores in unseen data from regional functional connectivity, while controlling for in-scanner motion, age, and sex. The trained model was further tested on data from HCP-D without further tuning. Finally, we tested how the connectivity patterns associated with BPD aligned with agerelated changes in connectivity.ResultsMultivariate functional connectivity patterns significantly predicted out-of-sample BPD proxy scores in unseen data in both young adults (HCP-YA;pperm= 0.001) and older adolescents (HCP-D;pperm= 0.001). Predictive capacity of regions was heterogeneous; the most predictive regions were found in functional systems relevant for emotion regulation and executive function, including the ventral attention network. Finally, regional functional connectivity patterns that predicted BPD proxy scores aligned with those associated with development in youth.ConclusionIndividual differences in functional connectivity in developmentally-sensitive regions are associated with the symptoms of BPD.
Environmental DNA (eDNA) metabarcoding differentiates between micro-habitats within the rocky intertidal
Authors: Shea Meghan M. , Boehm Alexandria B. 
Published: August 2023

AbstractWhile the utility of environmental DNA (eDNA) metabarcoding surveys for biodiversity monitoring continues to be demonstrated, the spatial and temporal variability of eDNA, and thus the limits of the differentiability of an eDNA signal, remains under-characterized. In this study, we collected eDNA samples from distinct micro-habitats (∼40 m apart) in a rocky intertidal ecosystem over their exposure period in a tidal cycle. During this period, the micro-habitats transitioned from being interconnected, to physically isolated, to interconnected again. Using a well-established eukaryotic (cytochrome oxidase subunit I) metabarcoding assay, we detected 415 species across 28 phyla. Across a variety of univariate and multivariate analyses, using just taxonomically-assigned data as well as all detected amplicon sequence variants (ASVs), we identified unique eDNA signals from the different micro-habitats sampled. This differentiability paralleled ecological expectations and increased as the sites became more physically disconnected. Our results demonstrate that eDNA biomonitoring can differentiate micro-habitats in the rocky intertidal only 40 m apart, that these differences are ecologically meaningful, and that physical connectivity informs the degree of differentiation possible. These findings showcase the potential power of eDNA biomonitoring to increase the spatial and temporal resolution of marine biodiversity data, aiding research, conservation, and management efforts.
Restoration of locomotor function following stimulation of the A13 region in Parkinson’s mouse models
Authors: Kim Linda H. , Lognon Adam P. , Sharma Sandeep , Tran Michelle A. , Badenhorst Cecilia , Chomiak Taylor , Tam Stephanie , McPherson Claire , Stang Todd E. , Eaton Shane E. A. , Kiss Zelma H. T. , Whelan Patrick J. 
Published: August 2023

ABSTRACTParkinson’s disease (PD) is characterized by extensive motor and non-motor dysfunction, including gait disturbance, which is difficult to treat effectively. This study explores the therapeutic potential of targeting the A13 region, a heterogeneous region of the medial zona incerta (mZI) containing dopaminergic, GABAergic, and glutamatergic neurons that has shown relative preservation in PD models. The A13 is identified to project to the mesencephalic locomotor region (MLR), with a subpopulation of cells displaying activity correlating to movement speed, suggesting its role in locomotion. We show that photoactivation of this A13 region can alleviate bradykinesia and akinetic features, while increasing turning in a mouse model of PD. These effects combine disease-specific rescue of function with a possible gain of function. We identified areas of preservation and plasticity within the mZI connectome using whole-brain imaging. Our findings suggest a global remodeling of afferent and efferent projections of the A13 region, highlighting the zona incerta’s role as a crucial hub for the rapid selection of motor function. The study unveils the significant pro-locomotor effects of the A13 region and suggests its promising potential as a therapeutic target for PD-related gait dysfunction.SIGNIFICANCE STATEMENTThis work examines the function of the A13 region in locomotion, an area with direct connectivity to locomotor regions in the brainstem. A13 stimulation can restore locomotor function and improve bradykinesia in a PD mouse model.
Model-based inference of RNA velocity modules improves cell fate prediction
Authors: Aivazidis Alexander , Memi Fani , Kleshchevnikov Vitalii , Clarke Brian , Stegle Oliver , Bayraktar Omer Ali 
Published: August 2023

AbstractRNA velocity is a powerful paradigm that exploits the temporal information contained in spliced and unspliced RNA counts to infer transcriptional dynamics. Existing velocity models either rely on coarse biophysical simplifications or require extensive numerical approximations to solve the underlying differential equations. This results in loss of accuracy in challenging settings, such as complex or weak transcription rate changes across cellular trajectories. Here, we present cell2fate, a formulation of RNA velocity based on alinearizationof the velocity ODE, which allows solving a biophysically accurate model in a fully Bayesian fashion. As a result, cell2fate decomposes the RNA velocity solutions intomodules, which provides a new biophysical connection between RNA velocity and statistical dimensionality reduction. We comprehensively benchmark cell2fate in real-world settings, demonstrating enhanced interpretability and increased power to reconstruct complex dynamics and weak dynamical signals in rare and mature cell types. Finally, we apply cell2fate to a newly generated dataset from the developing human brain, where we spatially map RNA velocity modules onto the tissue architecture, thereby connecting the spatial organisation of tissues with temporal dynamics of transcription.
Bulky glycocalyx drives cancer invasiveness by modulating substrate-specific adhesion
Authors: Barai Amlan , Piplani Niyati , Gomathi V , Ghogale Mayank M , Kumar Sushil , Kulkarni Madhura , Sen Shamik 
Published: August 2023

AbstractMajority of the eukaryotic cell surface is decorated with a layer of membrane attached polysaccharides and glycoproteins collectively referred to as the glycocalyx. While formation of a bulky glycocalyx has been associated with cancer progression, the mechanisms by which the glycocalyx regulates cancer invasiveness is incompletely understood. We address this question by first documenting sub-type specific expression of the major glycocalyx glycoprotein Mucin-1 (MUC1) in breast cancer patient samples and breast cancer cell lines. Strikingly, glycocalyx disruption led to inhibition of 2D motility, loss of 3D invasion and reduction of clonal scattering of breast cancer cells at the population level. Tracking of 2D cell motility and 3D invasiveness of MUC1-based sorted sub-populations revealed fastest motility and invasiveness in intermediate MUC1-expressing cells, with glycocalyx disruption abolishing these effects. While differential sensitivity in 2D motility is attributed to a non-monotonic dependence of focal adhesion size on MUC1 levels, higher MUC1 levels enhance 3D invasiveness via increased traction generation. In contrast to inducing cell rounding on collagen-coated substrates, high MUC1 level promotes cell adhesion and confers resistance to shear flow on substrates coated with the endothelial surface protein E-selectin. Collectively, our findings illustrate how MUC1 drives cancer invasiveness by differentially regulating cell-substrate adhesion in a substrate-dependent manner.
Cross-pollination is more important than gibberellin application in the germination of the everlasting flowers ofJaneirona carrasqueira(morphotype ofComanthera bisulcata)
Authors: de Azevedo Maria Luiza , Oliveira Maria Neudes Sousa de , Rech André Rodrigo , Barbosa Jose Carlos , Gorgens Eric Bastos , Machado Evandro Luiz Mendonça , Pereira Israel Marinho 
Published: August 2023

AbstractThe “sempre-vivas” are plants known as “everlasting flowers” because they have inflorescences that retain the appearance of living structures even after being harvested and dried. Given their ornamental potential, some species are widely exploited commercially, and their production occurs almost exclusively through extractivism. However, data on their pollination, reproduction, and germination are limited. Extractivism is an activity of great importance for the residents of the Espinhaço Meridional municipalities, and research is essential for establishing plans and proposals for the management of these native species. Given this scenario, we studied the pollinators and the importance of cross- and autogamy for reproductive success ofJaneirona carrasqueira(morphotype ofComanthera bisulcata(Körn) L.R. Parra & Giul), commercially collected in Diamantina, Minas Gerais. We also evaluated germination and the influence of the exogenous application of gibberellin (GA3) on seeds. Pollinators were observed during the flowering period in beds cultivated with this species in the native Campo Rupestre area of Diamantina, Minas Gerais. The inflorescences of the species were collected from two different environments: one isolated from pollinating insects (inside the greenhouse), and the other open in the presence of pollinators. The seeds were removed from the flower heads and subjected to exogenous application of gibberellin (0–control and 500 ppm). The flowers showed a generalist pollination strategy, including visitors who collected pollen and nectar as well as those who exclusively collected nectar. For germination, the most influential factor was cross-pollination and not gibberellin application. We conclude that the pollination system represents a determining mechanism and is a very important factor to be considered in management plans aimed at species conservation.Highlights–Comanthera bisulcataemploys a generalist pollination strategy.– The pollination system is a crucial mechanism for germination.– Cross-pollination is more important than gibberellin application– Reproduction is a crucial aspect to be taken into account in the management plans of the species.
Evaluation of the Ability of AlphaFold to Predict the Three-Dimensional Structures of Antibodies and Epitopes
Authors: Polonsky Ksenia , Pupko Tal , Freund Natalia T 
Published: August 2023

AbstractBeing able to accurately predict the three-dimensional structure of an antibody can facilitate fast and precise antibody characterization and epitope prediction, with important diagnostic and clinical implications. In the current study, we evaluate the ability of AlphaFold to predict the structures of 222 recently published, non-redundant, high resolution Fab heavy and light chain structures of antibodies from different species (human,Macaca mulatta, mouse, rabbit, rat) directed against different antigens. Our analysis reveals that while the overall prediction quality of antibody chains is in line with the results available in CASP14, other antibody regions like the complementarity-determining regions (CDRs) of the heavy chain, which are prone to higher genetic variation, generate a less accurate prediction. Moreover, we discovered that AlphaFold often mis-predicts the bending angles between the variable and constant domains within a Fab. To evaluate the ability of AlphaFold to model antibody:antigen interactions based only on sequence, we used AlphaFold-multimer in combination with ZDOCK docking to predict the structures of 26 known antibody:antigen complexes. ZDOCK succeeded in predicting 11, and AlphaFold only two, out of 26 models with medium or high accuracy, with significant deviations in the docking contacts predicted in the rest of the molecules. In summary, our study provides important information about the abilities and limitations of using AlphaFold to predict antibody:antigen interactions and suggests areas for possible improvement.Key PointsAlphaFold was used to predict 222 new 3D hi-res atomic structures of Ab chains.Low accuracy was observed in the prediction of HC-CDR3 and the elbow angles.Predicting Ab-Ag complexes and epitope mapping using AlphaFold-Multimer was limited.
scMD: cell type deconvolution using single-cell DNA methylation references
Authors: Cai Manqi , Zhou Jingtian , McKennan Chris , Wang Jiebiao 
Published: August 2023

AbstractThe proliferation of single-cell RNA sequencing data has led to the widespread use of cellular deconvolution, aiding the extraction of cell type-specific information from extensive bulk data. However, those advances have been mostly limited to transcriptomic data. With recent development in single-cell DNA methylation (scDNAm), new avenues have been opened for deconvolving bulk DNAm data, particularly for solid tissues like the brain that lack cell-type references. Due to technical limitations, current scDNAm sequences represent a small proportion of the whole genome for each single cell, and those detected regions differ across cells. This makes scDNAm data ultrahigh dimensional and ultra-sparse. To deal with these challenges, we introduce scMD (single cell Methylation Deconvolution), a cellular deconvolution framework to reliably estimate cell type fractions from tissue-level DNAm data. To analyze large-scale complex scDNAm data, scMD employs a statistical approach to aggregate scDNAm data at the cell cluster level, identify cell-type marker DNAm sites, and create a precise cell-type signature matrix that surpasses state-of-the-art sorted-cell or RNA-derived references. Through thorough benchmarking in several datasets, we demonstrate scMD’s superior performance in estimating cellular fractions from bulk DNAm data. With scMD-estimated cellular fractions, we identify cell type fractions and cell type-specific differentially methylated cytosines associated with Alzheimer’s disease.
Quantification of sporozoite expelling byAnophelesmosquitoes infected with laboratory and naturally circulatingP. falciparumgametocytes
Authors: Andolina Chiara , Graumans Wouter , Guelbeogo Moussa , van Gemert Geert Jan , Ramjith Jordache , Harouna Soré , Soumanaba Zongo , Stoter Rianne , Vegte-Bolmer Marga , Pangos Martina , Sinnis Photini , Collins Katharine , Staedke Sarah G , Tiono Alfred B , Drakeley Chris , Lanke Kjerstin , Bousema Teun 
Published: August 2023

AbstractIt is currently unknown whether allPlasmodium falciparuminfected mosquitoes are equally infectious. We assessed sporogonic development using cultured gametocytes in the Netherlands and naturally circulating strains in Burkina Faso. We quantified the number of sporozoites expelled into artificial skin in relation to intact oocysts, ruptured oocysts, and residual salivary gland sporozoites. Sporozoites were quantified by highly sensitive qPCR; intact and ruptured oocysts by fluorescence microscopy following antibody staining of circumsporozoite protein. In laboratory conditions, higher total sporozoite burden in mosquitoes was associated with a shorter duration of sporogony (p<0.001). Overall, 53% (116/216) ofP. falciparuminfectedAn. stephensimosquitoes expelled sporozoites into artificial skin. The medians of expelled and residual salivary gland sporozoites were 136 (IQR: 34-501) and 23,947 (IQR: 9127-78,380), respectively. There was a strong positive correlation between ruptured oocyst number and salivary gland sporozoite load (ρ=0.8; p<0.0001) and a weaker positive correlation between salivary gland sporozoite load and the number of sporozoites expelled (ρ=0.35; p=0.0002). In Burkina Faso,An. coluzziimosquitoes were infected by natural gametocyte carriers. Among mosquitoes that were salivary gland sporozoite positive, 89% (33/37) expelled sporozoites with a median of 1035 expelled sporozoites (IQR: 171-2969) and harbored a median of 45,100 residual salivary gland sporozoites (IQR: 20,310-164,900). Again, we observed a strong correlation between ruptured oocyst number and salivary gland sporozoite load (ρ=0.9; p<0.0001) and a positive correlation between salivary gland sporozoite load and the number of sporozoites expelled (ρ=0.7; p<0.0001). Mosquito salivary glands in Burkina Faso harbored 1-3 distinct parasite clones; several mosquitoes expelled multiple parasite clones during probing.Whilst sporozoite expelling was regularly observed from mosquitoes with low infection burdens, our findings indicate that mosquito infection burden is associated with the number of expelled sporozoites. Future work is required to determine the direct implications of these findings for transmission potential.
An adaptable, reusable, and light implant for chronic Neuropixels probes
Authors: Bimbard C. , Takács F. , Catarino J. A. , Fabre J. M. J. , Gupta S. , Lenzi S. C. , Melin M. D. , O’Neill N. , Orsolic I. , Robacha M. , Street J. S. , Teixeira J. , Townsend S. , van Beest E. H. , Zhang A. M. , Churchland A. K. , Duan C. A. , Harris K. D. , Kullmann D. M. , Lignani G. , Mainen Z. F. , Margrie T. W. , Rochefort N.L. , Wikenheiser A. M. , Carandini M. , Coen P. 
Published: August 2023

AbstractElectrophysiology has proven invaluable to record neural activity, and the development of Neuropixels probes dramatically increased the number of recorded neurons. These probes are often implanted acutely, but acute recordings cannot be performed in freely moving animals and the recorded neurons cannot be tracked across days. To study key behaviors such as navigation, learning, and memory formation, the probes must be implanted chronically. An ideal chronic implant should (1) allow stable recordings of neurons for weeks; (2) allow reuse of the probes after explantation; (3) be light enough for use in mice. Here, we present the “Apollo Implant”, an open-source and editable device that meets these criteria and accommodates up to two Neuropixels 1.0 or 2.0 probes. The implant comprises a “payload” module which is attached to the probe and is recoverable, and a “docking” module which is cemented to the skull. The design is adjustable, making it easy to change the distance between probes, the angle of insertion, and the depth of insertion. We tested the implant across eight labs in head-fixed mice, freely moving mice, and freely moving rats. The number of neurons recorded across days was stable, even after repeated implantations of the same probe. The Apollo implant provides an inexpensive, lightweight, and flexible solution for reusable chronic Neuropixels recordings.
Ribosomal DNA copy number is associated with body mass in humans and other mammals
Authors: Law Pui Pik , Rodriguez-Algarra Francisco , Asenius Fredrika , Gregori Maria , Seaborne Robert AE , Yildizoglu Selin , Miller James RC , Mesnage Robin , Antoniou Michael N , Li Weilong , Tan Qihua , Hillman Sara L , Rakyan Vardhman K , Williams David J , Holland Michelle L 
Published: August 2023

SUMMARYBody mass results from a complex interplay between genetics and environment. The contribution of genetic variation to body mass has been extensively studied, but due to the technical limitations of platforms used for population scale studies, repetitive parts of the genome have not previously been considered. Here we applied genome-wide approaches to identify an association between adult body mass and the copy number (CN) of 45S-ribosomal DNA (rDNA). rDNA codes for the rRNA components of the ribosome and exists in hundreds of copies/cell in mammals. Inter-individual variation in rDNA CN has not previously been documented but has not been associated with a mammalian phenotype. Here, we show that germ-line inherited rDNA CN is associated with post-pubertal growth rate in rats and BMI in adult humans. rDNA CN variation is not associated with rRNA transcription rates in adult tissues, suggesting the mechanistic link occurs earlier in development. This is supported by our observation that it is growth rate and body mass, rather than obesity that are associated with copy number and that these phenotypes emerge prior to adulthood. We present hypotheses for future investigation into the mechanistic basis of this association.
The black-legged tickIxodes scapularisdetects CO2without the Haller’s organ
Authors: Städele Carola 
Published: August 2023

ABSTRACTBoth male and female ticks have a strong innate drive to find and blood-feed on hosts. Carbon dioxide (CO2) is considered a critical behavioral activator and attractant for ticks and an essential sensory cue to find hosts. Yet, how CO2activates and promotes host-seeking in ticks is poorly understood. We studied CO2responses in the black-legged tickIxodes scapularis, the primary vector for Lyme disease in North America. Adult males and females were exposed to 1, 2, 4, or 8% CO2, and changes in walking behavior and foreleg movement were analyzed. We find that CO2is a potent stimulant for adultIxodes scapularis, even at lower concentrations (1%). Behavioral reactions depend on the animal’s state: Walking ticks increase their walking speed, while stationary ticks start to wave their forelegs and begin to quest – both behaviors resembling aspects of host-seeking. Furthermore,Ixodes scapularishas no clear concentration preference and is not tuned more robust to breath-like CO2concentrations (∼4%) than to the other concentrations tested. As soon as the CO2level is above a certain threshold,Ixodes scapularisreact, indicating that CO2acts as a behavioral activator and can be used as a long-distance cue to detect approaching hosts. Moreover, we provide convincing evidence that the foreleg Haller’s organ is not necessary for CO2detection. Even with disabled or amputated Haller’s organ,Ixodes scapularisrespond robustly to CO2, signifying that there must be CO2-sensitive structures important for tick host-seeking that have not yet been identified.