bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interoceptive signals shape the earliest markers and neural pathway to awareness at the visual threshold
Authors: Leupin Viviana , Britz Juliane 
Published: July 2023

AbstractVariations in interoceptive signals from the baroreceptors (BRs) across the cardiac and respiratory cycle can modulate cortical excitability and so affect awareness. It remains debated at what stages of processing they affect awareness-related event-related potentials (ERPs) in different sensory modalities. We investigated the influence of the cardiac (systole/diastole) and the respiratory (inhalation/exhalation) phase on awareness-related ERPs. Subjects discriminated visual threshold stimuli while their electroencephalogram (EEG), electrocardiogram (ECG) and respiration were simultaneously recorded. We compared ERPs and their intracranial generators for stimuli classified correctly with and without awareness as a function of the cardiac and respiratory phase. Cyclic variations of interoceptive signals from the baroreceptors (BRs) modulated both the earliest electrophysiological markers and the trajectory of brain activity when subjects became aware of the stimuli: an early sensory component (P1) was the earliest marker of awareness for low (diastole/inhalation) and a perceptual component (visual awareness negativity, VAN) for high (systole/exhalation) BR activity, indicating that BR signals interfere with the sensory processing of the visual input. Likewise, activity spread from the primary visceral cortex (posterior insula) to posterior parietal cortices during high and from associative interoceptive centers (anterior insula) to prefrontal cortex during low BR activity. Consciousness is thereby resolved in cognitive/associative regions when BR is low and in perceptual centers when it is high. Our results suggest that cyclic fluctuations of BR signaling affect both the earliest markers of awareness and the brain processes underlying conscious awareness.Significance StatementThe brain continuously processes stimuli from inside and outside the body, and interoceptive stimuli can modulate the perception of external stimuli. Cardiac and respiratory rhythms are important pacemakers of the organism, and we show how they shape awareness-related brain activity for visual threshold stimuli in two ways. Variations of baroreceptor (BR) activity across the cardiac and respiratory cycle affect 1) the earliest electrophysiological marker (P1 for low (diastole/inhalation), VAN for high (systole/exhalation) BR activity) and 2) the brain areas activated (frontal cortex for low and parietal cortex for high BR activity) when subjects become aware of a stimulus. Cyclic variations of bodily signal can modulate cortical excitability and so shape the pathway to awareness and we propose to consider them as functionally relevant signals rather dismissing them as noise.
Differential Adaptation and Remodeling of the Tumor Microenvironment in Breast Cancer Cells During the Stages of Brain Metastasis
Authors: Wu Xinquan , Zhang Yan , Huang Zhenyong , Li Nan 
Published: July 2023

AbstractObjectiveTo integrate macro-transcriptomics and single-cell sequencing to analyze the differential gene expression between primary and brain metastatic breast cancer cells, as well as between active and dormant cancer cells within brain metastases, exploring their adaptation and remodeling abilities at different stages of brain metastasis.MethodsFour public datasets were used: three mRNA microarray datasets from breast cancer and brain metastasis tissues, and one single-cell RNA sequencing (scRNA-seq) dataset from active and dormant brain metastatic cells. Gene differential expression, pathway enrichment, and cell clustering analyses were performed to compare primary and metastatic breast cancer cells, as well as active and dormant cells in brain metastases, focusing on gene expression, metabolic pathways, and functional pathways.ResultsMetastatic breast cancer cells showed weakened pathways related to the extracellular matrix and protein digestion. Active cells exhibited enhanced cell cycle regulation, tumor proliferation, and hypoxia resistance pathways compared to dormant cells. Clustering analysis revealed that cluster 6, unique to dormant cells, had enhanced functions in epithelial-mesenchymal transition (EMT), extracellular matrix (ECM), collagen formation, tumor inflammation siganure (TIS), and IL-10 signaling. Cluster 3 and 4 in active cells had enhanced DNA replication and tumor proliferation pathways, respectively.ConclusionThis study highlights the role of cancer cell characteristics and heterogeneity in the invasiveness of brain metastasis. Understanding these mechanisms can guide the development of more effective treatment strategies for breast cancer brain metastasis (BCBM) patients.
From goal to outcome: analyzing the progression of biomedical sciences PhD careers in a longitudinal study using an expanded taxonomy
Authors: Brown Abigail M. , Meyers Lindsay C. , Varadarajan Janani , Ward Nicholas J. , Cartailler Jean-Philippe , Chalkley Roger G. , Gould Kathleen L. , Petrie Kimberly A. 
Published: July 2023

AbstractBiomedical sciences PhDs pursue a wide range of careers inside and outside academia. However, there is little data regarding how career interests of PhD students relate to the decision to pursue postdoctoral training or to their eventual career outcomes. Here, we present the career goals and career outcomes of 1,452 biomedical sciences PhDs who graduated from Vanderbilt University between 1997-2021. We categorized careers using an expanded three-tiered taxonomy and flags that delineate key career milestones. We also analyzed career goal changes between matriculation and defense, and the reasons why students became more- or less-interested in research-intensive faculty careers. We linked students’ career goal at defense to whether they did a postdoc, the duration of time between defense and the first non-training position, the career area of the first non-training position, and the career area of the job at ten years after graduation. Finally, we followed individual careers for ten years after graduation to characterize movement between different career areas over time. We found that most students changed their career goal during graduate school, declining numbers of alumni pursued postdoctoral training, many alumni entered first non-training positions in a different career area than their goal at defense, and the career area of the first non-training position was a good indicator of the job that alumni held 10 years after graduation. Our findings emphasize that students need a wide range of career development opportunities and career mentoring during graduate school to prepare them for futures in research and research-related professions.
Differences in cortical surface area in developmental language disorder
Authors: Bahar Nilgoun , Cler Gabriel J , Krishnan Saloni , Asaridou Salomi S , Smith Harriet J , Willis Hanna E , Healy Máiréad P , Watkins Kate E 
Published: July 2023

ABSTRACTApproximately seven per cent of children have developmental language disorder (DLD), a neurodevelopmental condition associated with persistent language learning difficulties without a known cause. Our understanding of the neurobiological basis of DLD is limited. Here, we used FreeSurfer to investigate cortical surface area and thickness in 54 children and adolescents with DLD and 74 age-matched controls aged 10-16 years. We also examined cortical asymmetries in DLD using an automated surface-based technique. Those with DLD showed smaller surface area bilaterally in the inferior frontal gyrus extending to the anterior insula, in the posterior temporal and ventral occipito-temporal cortex, and in portions of the anterior cingulate and superior frontal cortex. There were no differences in cortical thickness, nor in asymmetry of these cortical metrics. Post-hoc exploratory analyses revealed that surface area in the left fusiform and inferior frontal cortex related to children’s reading and non-word repetition scores, respectively. This study highlights the importance of distinguishing between surface area and cortical thickness in investigating the brain basis of neurodevelopmental disorders and suggests the development of cortical surface area to be of importance to DLD. Future longitudinal studies are required to understand the developmental trajectory of these cortical differences in DLD and how they relate to language maturation.
Multivalent Exosome based protein vaccine: a “mix and match” approach to epidemic viruses’ challenges
Authors: Cacciottolo Mafalda , Hsieh Li-En , Li Yujia , LeClaire Michael J. , Nice Justin B , Twaddle Ryan , Mora Ciana , Young Meredith , Angeles Jenna , Lau Christy , Jin Cindy , Elliott Kristi , Sun Minghao 
Published: July 2023

ABSTRACTEndemic viruses are becoming increasingly the norm, and the development of a rapid and effective vaccine is emergent. Here, we used our StealthX ™ exosome platform to express either Influenza H3 (Stealth™ X-Hemagglutinin, STX-H3) or SARS-CoV-2 Delta spike (Stealth™ X-Spike, STX-S) protein on the surface and facilitate their trafficking to the exosomes. When administered as single product, both STX-H3 and STX-S induced a strong immunization with the production of a potent humoral and cellular immune response in mice. Interestingly, these effects were obtained with administration of nanograms of protein and without adjuvant. Therefore, we tested the possibility of a multivalent vaccine: STX-H3 and STX-S exosomes were formulated together in a “mix and match” approach and the immune response was further evaluated. We showed that our STX-H3+S cocktail vaccine is as effective as the single components administered separately, resulting in a strong antibody and T-cell response. Our data show that our exosome platform has an enormous potential to revolutionize vaccinology by rapidly facilitating antigen presentation, and for therapeutics by enabling cell and tissue specific targeting.
Neural representation of spatial and non-spatial auditory attention in EEG signals
Authors: An Winko W. , Noyce Abigail , Pei Alexander , Shinn-Cunningham Barbara 
Published: July 2023

AbstractNeural representation, capturing the content and format of encoded information, provides insight into the internal states of neural units. Studies of neural representation contrast with studies of neural processes, which focus on how one neural unit influences another. Representational similarity analysis (RSA), a multivariate analysis approach, has been used in previous studies to explore the neural representation of object categories in various neuroimaging modalities. In this study, we employed RSA to examine the neural representation of executive function. We designed an experiment involving a rich set of conditions where participants engaged in an auditory task requiring either spatial or non-spatial attention. We extracted representational features from their electroencephalography (EEG) scalp voltage and alpha power and compared these features with ideal conceptual models representing perfect categorization of different attentional states. The results demonstrate the feasibility of investigating internal cognitive states using RSA. Specifically, we identified time intervals during which attentional state contrasts, such as differences between attention types or locations, manifested in the measured neural responses from scalp voltage and alpha power distributions.
Amplicon-guided isolation and cultivation of previously uncultured microbial species from activated sludge
Authors: Verhoeven Maarten D. , Nielsen Per H. , Dueholm Morten K. D. 
Published: July 2023

AbstractMicrobes are fundamental for biological wastewater treatment. However, most microbial species found in activated sludge (AS) from wastewater treatment plants (WWTPs) have never been isolated and grown as pure cultures, thus limiting our understanding of the underlying biological processes. To change this, we here introduce an experimental setup where the plating of dispersed AS bacteria are combined with 16S rRNA gene amplicon sequencing of total plate biomass for rapid identification of growth conditions that allow for the isolation of key microbial species in AS. We show that agarose plates composed of AS fluid supplemented with various carbon sources support the growth of many previously uncultivated AS bacteria. To confirm that the approach can also be used to isolate previously uncultured species, we picked 200 colonies from the plates for growth in liquid medium. This resulted in 185 growing cultures representing 102 strains based on unique 16S rRNA gene V1-V3 amplicon sequence variants (ASVs). Classification of the ASVs with the MiDAS 4 database revealed 48 distinct genera, including the previously uncultured AAP99,Ca. Propionivibrio, Ellin6067, midas_g_12, andCa. Brachybacter. Among the ASVs that obtained species-level classification, we observed 43 unique species of which 29 were only classified based on the MiDAS placeholder taxonomy highlighting the potential for culturing many novel taxa. Preparation of glycerol stocks and subsequent validation by restreaking on plates resulted in 10 pure cultures of which six represent core or conditional rare or abundant (CRAT) species observed within the MiDAS global survey of WWTPs.ImportanceBiological wastewater treatment relies on complex microbial communities that assimilate nutrients and break down pollutants in the wastewater. Knowledge about the physiology and metabolism of bacteria in wastewater treatment plants (WWTPs) may therefore be used to improve the efficacy and economy of wastewater treatment. Our current knowledge is largely based on 16S rRNA gene amplicon profiling, fluorescence in situ hybridization studies, and predictions based on metagenome-assembled genomes. Bacterial isolates are often required to validate genome-based predictions as they allow researchers to analyze a specific species without interference from other bacteria and with simple bulk measurements. Unfortunately, there are currently very few pure cultures of microbes commonly found in WWTPs. To address this, we introduce an isolation strategy that takes advantage of state-of-the-art microbial profiling techniques to uncover suitable growth conditions for key WWTP microbes. We furthermore demonstrate that this information can be used to isolate key organisms representing global WWTPs.
CRIMP: A CRISPR/Cas9 Insertional Mutagenesis Protocol and the CRIMP Toolkit
Authors: Miles Lee B , Calcinotto Vanessa , Sonntag Carmen , Lee Clara , Bryson-Richardson Robert J 
Published: July 2023

AbstractWe developed a highly efficient targeted insertional mutagenesis system, CRIMP, and an associated plasmid toolkit, CRIMPkit, that disrupts native gene expression by inducing complete transcriptional termination to produce null mutant alleles without inducing genetic compensation. The CRIMPkit contains over 30 ready-to-use plasmid vectors allowing easy and complete mutagenesis of any gene in any reading frame without requiring custom sequences, modification, or subcloning, and also provides a fluorescent readout of successfully mutagenised fish.
Amyloid β accelerates age-related proteome-wide protein insolubility
Authors: Anderton Edward , Chamoli Manish , Bhaumik Dipa , King Christina D. , Xie Xueshu , Foulger Anna , Andersen Julie K. , Schilling Birgit , Lithgow Gordon J. 
Published: July 2023

AbstractLoss of proteostasis is a highly conserved feature of aging across model organisms and typically results in the accumulation of insoluble protein aggregates. Protein insolubility is a central feature of major age-related neurodegenerative diseases, including Alzheimer’s Disease (AD), where hundreds of insoluble proteins associate with aggregated amyloid beta (Aβ) in senile plaques. Moreover, proteins that become insoluble during aging in model organisms are capable of accelerating Aβ aggregation in vitro. Despite the connection between aging and AD risk, therapeutic approaches to date have overlooked aging-driven protein insolubility as a contributory factor. Here, using an unbiased proteomics approach, we questioned the relationship between Aβ and age-related protein insolubility. We demonstrate that Aβ expression drives proteome-wide protein insolubility in C. elegans and this insoluble proteome closely resembles the insoluble proteome driven by normal aging, suggesting the possibility of a vicious feedforward cycle of aggregation in the context of AD. Importantly, using human genome-wide association studies (GWAS), we show that the CIP is replete with biological processes implicated not only in neurodegenerative diseases but also across a broad array of chronic, age-related diseases (CARDs). This provides suggestive evidence that age-related loss of proteostasis could play a role in general CARD risk. Finally, we show that the CIP is enriched with proteins that modulate the toxic effects of Aβ and that the gut-derived metabolite, Urolithin A, relieves Aβ toxicity, supporting its use in clinical trials for dementia and other age-related diseases.
In vivo imaging in transgenic songbirds reveals superdiffusive neuron migration in the adult brain
Authors: Shvedov Naomi R. , Analoui Sina , Dafalias Theresia , Bedell Brooke L. , Gardner Timothy J. , Scott Benjamin B. 
Published: July 2023

SummaryNeuron migration is a key phase of neurogenesis, critical for the assembly and function of neuronal circuits. In songbirds, this process continues throughout life, but how these newborn neurons disperse through the adult brain is unclear. We addressed this question usingin vivotwo-photon imaging in transgenic songbirds that express GFP in young neurons. In juvenile and adult birds, migratory cells were present at a high density, traveled in all directions, and made frequent course changes. Notably, these dynamic migration patterns were well fit by a superdiffusive model. Simulations revealed that these diffusion-like dynamics were sufficient to disperse new neurons throughout the song nucleus HVC. These results suggest that diffusion-like migration may underlie the formation and maintenance of nuclear brain structures in the postnatal brain and indicate that transgenic songbirds are a useful resource for future studies into the mechanisms of adult neurogenesis.HighlightsTransgenic songbirds express GFP in a neurogenic lineageGFP expression is strong and sparse enough to track single cellsin vivoAdult neuron migration is well fit by a superdiffusive modelSuperdiffusive migration is sufficient to populate HVC in simulation
Find, Label, Annotate Genomes: FLAG, a fully automated tool for structural and functional gene annotation
Authors: Troy William , Damas Joana , Titus Alexander J. , Cantarel Brandi L. 
Published: July 2023

AbstractRecent advances in long-read sequencing technologies and the efforts of projects aimed at increasing the universe of sequenced reference genomes have led to a growth in the number of whole genomes sequenced for non-model organisms. Still, 81% of the over 36,000 unique publicly available eukaryotic genomes in the NCBI database lack gene structure annotations (1). While there are many open-source tools available for each step in the annotation process, many of these tools are designed for chromosomal assemblies with available transcript data from the same or very closely related organisms. Here we present “Find, Label, Annotate Genomes” (FLAG), a fully automated genome annotation workflow. FLAG (i) works on any computing environment, (ii) runs automatically without initial training data, (iii) generates structural and functional annotations, (iv) performs accurately with fragmented genomes, (v) does not require species-specific extrinsic evidence (transcript sequences) and (vi) includes quality control steps to evaluate annotation completeness. We compared the gene annotations generated by FLAG and publicly available annotations from 12 eukaryotic organisms, including 1 plant, 8 living animals, and 1 extinct animal. In fragmented genomes, FLAG annotations provided an average of 18% increase in complete BUSCO scores and 15x lower error rate for the predicted number of protein-coding genes when compared to published BRAKER2 annotations. With FLAG-Refiner further improved results by decreasing the error rate to 17x lower when compared to published BRAKER2 annotations. In high-quality model organisms, FLAG demonstrates comparable results to those of the NCBI EGAP pipeline, underscoring its robustness and accuracy in gene prediction across diverse taxa and assembly qualities.
Evolving together: Cassandra retrotransposons gradually mirror promoter mutations of the 5S rRNA genes
Authors: Maiwald Sophie , Mann Ludwig , Garcia Sònia , Heitkam Tony 
Published: July 2023

AbstractThe 5S rRNA genes are among the most conserved nucleotide sequences across all species. Similar to the 5S preservation we observe the occurrence of 5S-related non-autonomous retrotransposons, so-called Cassandra. Cassandras harbor highly conserved 5S rDNA-related sequences within their long terminal repeats (LTRs), advantageously providing them with the 5S internal promoter. However, the dynamics of Cassandra retrotransposon evolution in the context of 5S rRNA gene sequence information and structural arrangement are still unclear, especially: 1) do we observe repeated or gradual domestication of the highly conserved 5S promoter by Cassandras and 2) do changes in 5S organization such as in the linked 35S-5S rDNA arrangements impact Cassandra evolution? Here, we show evidence for gradual co-evolution of Cassandra sequences with their corresponding 5S rDNAs. To follow the impact of 5S rDNA variability on Cassandra TEs, we investigate the Asteraceae family where highly variable 5S rDNAs, including 5S promoter shifts and both linked and separated 35S-5S rDNA arrangements have been reported. Cassandras within the Asteraceae mirror 5S rDNA promoter mutations of their host genome, likely as an adaptation to the host’s specific 5S transcription factors and hence compensating for evolutionary changes in the 5S rDNA sequence. Changes in the 5S rDNA sequence and in Cassandras seem uncorrelated with linked/separated rDNA arrangements. We place all these observations into the context of angiosperm 5S rDNA-Cassandra evolution, discuss Cassandra’s origin hypotheses (single or multiple) and Cassandra’s possible impact on rDNA and plant genome organization, giving new insights into the interplay of ribosomal genes and transposable elements.
SQuHIVLa: A novel assay for Specific Quantification of inducible HIV-1 reservoir by LAMP
Authors: Hossain Tanvir , Lungu Cynthia , de Schrijver Sten , Kuali Mamokoena , Rao Shringar , Ngubane Ayanda , Wai Kan Tsung , Palstra Robert-Jan , Madlala Paradise , Ndung’u Thumbi , Mahmoudi Tokameh 
Published: July 2023

SummaryStrategies toward HIV-1 cure aim to clear, inactivate, reduce or immunologically control the virus from a pool of latently infected cells such that combination antiretroviral therapy (cART) can be safely interrupted. In order to assess the impact of any putative curative interventions on the size and inducibility of the latent HIV-1 reservoir, robust and scalable assays are needed to precisely quantify the frequency of infected cells containing inducible replication competent HIV-1. Here, we present Specific Quantification of Inducible HIV-1 by LAMP (SQuHIVLa), a novel assay that leverages the high sensitivity and specificity of RT-LAMP, performed in a single reaction, to detect and quantify cells expressing Tat/Rev msRNA upon activation. Our LAMP primer/probe design exclusively detects subtype-specific HIV-1 Tat/Rev msRNA and exhibits high sensitivity, specificity, and reproducibility. Using SQuHIVLa we quantified the inducible viral reservoir in CD4+ T cells from a diverse group of people living with HIV-1 subtypes B and C on cART. SQuHIVLa presents a high throughput, scalable and specific HIV-1 reservoir quantification tool that is amenable to resource limited settings.