bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced stimulus-induced and stimulus-free gamma in open-eye meditators
Authors: Biswas Ankan , Aggarwal Srishty , Sharma Kanishka , Ray Supratim 
Published: February 2024

AbstractVisual stimuli induce “narrowband” gamma oscillations (30-70 Hz) that are linked to attention/binding and attenuate with aging and neurodegeneration. In contrast, meditation increases power in a broad frequency range (>25 Hz). However, the effect of meditation on stimulus-induced gamma is unknown. We recorded EEG from meditators and controls performing open-eye meditation while gamma-inducing stimuli were presented before, during and after meditation. We found that stimulus-induced gamma, like stimulus-free gamma, was stronger in meditators. Interestingly, both gamma signatures co-existed during meditation but were unrelated and prominent in occipital and fronto-temporal regions, respectively. Further, power spectral density (PSD) slope, which becomes shallower with aging, was steeper for meditators. Meditation could boost inhibitory mechanisms leading to stronger gamma and steeper PSDs, potentially providing protection against aging and neurodegeneration.One line summaryStimulus-induced and stimulus-free gamma are stronger in open-eye meditators.
Investigating the Intradermal Irritation Test of Hydrogel: A Study on Domestic Production
Authors: Odelabu Kehinde , Racheal Christianah 
Published: February 2024

AbstractThis study employs the intradermal injection method to assess the skin irritation potential of domestically produced medical hydrogel. Healthy white rabbits received intradermal injections of 0.5% sodium chloride solution (control), 0.5% sodium chloride extract, and olive oil extract as test samples. Erythema and edema were observed at 24 and 72 hours post-injection, and the primary irritation index was determined. Results revealed a primary irritation index of 0 for domestically produced hydrogel, indicating no skin irritation response.
A Neural Mechanism for Optic Flow Parsing in Macaque Visual Cortex
Authors: Peltier Nicole E. , Anzai Akiyuki , Moreno-Bote Ruben , DeAngelis Gregory C. 
Published: February 2024

AbstractFor the brain to compute object motion in the world during self-motion, it must discount the global patterns of image motion (optic flow) caused by self-motion. Optic flow parsing is a proposed visual mechanism for computing object motion in the world, and studies in both humans and monkeys have demonstrated perceptual biases consistent with the operation of a flow parsing mechanism. However, the neural basis of flow parsing remains unknown. We demonstrate, at both the individual unit and population levels, that neural activity in macaque area MT is biased by peripheral optic flow in a manner that can at least partially account for perceptual biases induced by flow parsing. These effects cannot be explained by conventional surround suppression mechanisms or choice-related activity, and have a substantial neural latency. Together, our findings establish the first neural basis for the computation of scene-relative object motion based on flow parsing.
Compositional transformations can reasonably introduce phenotype-associated values into sparse features
Authors: Austin George I. , Korem Tal 
Published: February 2024

AbstractIt was recently argued1that an analysis of tumor-associated microbiome data2is invalid because features that were originally very sparse (genera with mostly zero read counts) became associated with the phenotype following batch correction1. Here, we examine whether such an observation should necessarily indicate issues with processing or machine learning pipelines. We show counterexamples using the centered log ratio (CLR) transformation, which is often used for analysis of compositional microbiome data3. The CLR transformation has similarities to Voom-SNM4,5, the batch-correction method brought into question1,2, yet is a sample-wise operation that cannot, in itself, “leak” information or invalidate downstream analyses. We show that because the CLR transformation divides each value by the geometric mean of its sample, common imputation strategies for missing or zero values result in transformed features that are associated with the geometric mean. Through analyses of both synthetic and vaginal microbiome datasets we demonstrate that when the geometric mean is associated with a phenotype, sparse and CLR-transformed features will also become associated with it. We re-analyze features highlighted by Gihawi et al.1and demonstrate that the phenomenon of sparse features becoming phenotype-associated can also be observed after a CLR transformation, which serves as a counterexample to the claim that such an observation necessarily means information leakage. While we do not intend to address other concerns regarding tumor microbiome analyses1,6, validate Poore et al.’s2results, or evaluate batch-correction pipelines, we conclude that because phenotype-associated features that were initially sparse can be created by a sample-wise transformation that cannot artifactually inflate machine learning performance, their detection is not independently sufficient to demonstrate information leakage in machine learning pipelines. Microbiome data is multivariate, and as such, a value of zero carries a different meaning for each sample. Many transformations, including CLR and other batch-correction methods, are likewise multivariate, and, as these issues demonstrate, each individual feature should be interpreted with caution.
Hepatocyte differentiation requires anisotropic expansion of bile canaliculi
Authors: Belicova Lenka , Bebelman Maarten , Gralinska Elzbieta , Jumel Tobias , Lahree Aparajita , Shevchenko Andrej , Zatsepin Timofei , Kalaidzidis Yannis , Vingron Martin , Zerial Marino 
Published: February 2024

AbstractDuring liver development, bipotential progenitor cells called hepatoblasts differentiate into hepatocytes or cholangiocytes. Hepatocyte differentiation is uniquely associated with multi-axial polarity, enabling the anisotropic expansion of apical lumina between adjacent cells and formation of a three-dimensional network of bile canaliculi (BC). Cholangiocytes, the cells forming the bile ducts, exhibit the vectorial polarity common to epithelial cells. Whether and how cell polarization feeds back on the gene regulatory pathways governing hepatoblast differentiation is unknown. Here, we used primary hepatoblasts to investigate the contribution of anisotropic apical expansion to hepatocyte differentiation. Silencing of the small GTPase Rab35 caused isotropic lumen expansion and formation of multicellular cysts with the vectorial polarity of cholangiocytes. Gene expression profiling revealed that these cells express reduced levels of hepatocyte markers and upregulate genes associated with cholangiocyte identity. Time-course RNA sequencing demonstrated that loss of lumen anisotropy precedes these transcriptional changes. Independent alterations in apical lumen morphology induced either by modulation of the subapical actomyosin cortex or increased intraluminal pressure caused similar transcriptional changes. These findings suggest that cell polarity and lumen morphogenesis feedback to hepatoblast-to-hepatocyte differentiation.Summary statementDifferentiation of liver progenitors to functional hepatocytes requires anisotropic elongation of their nascent apical surfaces into tubular bile canaliculi.
A Telescopic Independent Component Analysis on Functional Magnetic Resonance Imaging Data Set
Authors: Mirzaeian Shiva , Faghiri Ashkan , Calhoun Vince D. , Iraji Armin 
Published: February 2024

AbstractBrain function can be modeled as the dynamic interactions between functional sources at different spatial scales, and each spatial scale can contain its functional sources with unique information, thus using a single scale may provide an incomplete view of brain function. This paper introduces a novel approach, termed “telescopic independent component analysis (TICA),” designed to construct spatial functional hierarchies and estimate functional sources across multiple spatial scales using fMRI data. The method employs a recursive ICA strategy, leveraging information from a larger network to guide the extraction of information about smaller networks. We apply our model to the default mode network (DMN), visual network (VN), and right frontoparietal network (RFPN). We investigate further on DMN by evaluating the difference between healthy people and individuals with schizophrenia. We show that the TICA approach can detect the spatial hierarchy of DMN, VS, and RFPN. In addition, TICA revealed DMN-associated group differences between cohorts that may not be captured if we focus on a single-scale ICA. In sum, our proposed approach represents a promising new tool for studying functional sources.Author summaryOur study introduces “telescopic independent component analysis (TICA)”, a novel approach using a recursive ICA strategy for exploring brain function across multiple spatial scales using fMRI data. TICA constructs spatial hierarchies and identifies functional sources such as default mode network (DMN), visual network (VN), and right frontoparietal network (RFPN). By applying TICA, we uncovered hierarchical structures within these networks and revealed differences in the DMN between healthy individuals and those with schizophrenia. This approach offers a promising new tool for studying function dynamics comprehensively.
Stability of N-type inactivation and the coupling between N-type and C-type inactivation in theAplysiaKv1 channel
Authors: Iwamuro Tokunari , Itohara Kazuki , Furukawa Yasuo 
Published: February 2024

AbstractThe voltage-dependent potassium channels (Kv channels) show several different types of inactivation. N-type inactivation is a fast inactivating mechanism, which is essentially an open pore blockade by the amino-terminal structure of the channel itself or the auxiliary subunit. There are several functionally discriminatable slow inactivation (C-type, P-type, U-type), the mechanism of which is supposed to include rearrangement of the pore region. In some Kv1 channels, the actual inactivation is brought about by coupling of N- type and C-type inactivation (N-C coupling). In the present study, we focused on the N-C coupling of theAplysiaKv1 channel (AKv1). AKv1 shows a robust N-type inactivation, but its recovery is almost thoroughly from C-type inactivated state owing to the efficient N-C coupling. In the I8Q mutant of AKv1, we found that the inactivation as well as its recovery showed two kinetic components apparently correspond to N-type and C-type inactivation. Also, the cumulative inactivation which depends on N-type mechanism in AKv1 was hindered in I8Q, suggesting that N-type inactivation of I8Q is less stable. We also found that Zn2+specifically accelerates C-type inactivation of AKv1, and that H382 in the pore turret is involved in the Zn2+binding. Because the region around Ile8(I8) in AKv1 has been suggested to be involved in the pre-block binding of the amino-terminal structure, our results strengthen a hypothesis that the stability of the pre-block state is important for stable N-type inactivation as well as the N-C coupling in the Kv1 channel inactivation.
ABCA1 deficiency causes tissue-specific dysregulation of the SREBP2 pathway in mice
Authors: Yamauchi Yoshio , Abe-Dohmae Sumiko , Iwamoto Noriyuki , Sato Ryuichiro , Yokoyama Shinji 
Published: February 2024

AbstractThe ATP-binding cassette transporter ABCA1 plays an essential role in the formation of high-density lipoprotein (HDL) by mediating phospholipid and cholesterol efflux to apolipoprotein A-I. In humans, loss-of-function mutations in theABCA1gene cause Tangier disease (TD), a familial HDL deficiency. In addition to the disappearance of HDL, TD patients andAbca1-/-mice exhibit the cholesterol deposition in peripheral tissues through a mechanism poorly understood, which may contribute to the development of premature atherosclerosis. We and others have shown that ABCA1 deficiency causes hyperactivation of the sterol regulatory element-binding protein 2 (SREBP2) pathwayin vitro. In this work, we investigate whether ABCA1 deficiency affects SREBP2-dependent cholesterol homeostatic responsesin vivo. We show that SREBP2 response gene expression is partly downregulated in the liver ofAbca1-/-mice compared to wild-type mouse livers in the steady-state condition. In contrast, we find that in fasted or refed condition, the expression of SREBP2 target genes is upregulated in multiple tissues ofAbca1-/-mice. Correspondently, SREBP2 processing is also increased in select tissues of these mice. Altogether, our results suggest that ABCA1 deficiency is associated with the tissue-specific dysregulation of the SREBP2 pathway in a manner dependent on nutritional status. Lack of ABCA1 thus causes not only HDL deficiency but also dysregulation of the SREBP2 pathway in multiple tissues, which may underlie the pathophysiology of TD.
Pangenome mining of theStreptomycesgenus redefines their biosynthetic potential
Authors: Mohite Omkar S. , Jørgensen Tue S. , Booth Thomas , Charusanti Pep , Phaneuf Patrick V. , Weber Tilmann , Palsson Bernhard O. 
Published: February 2024

AbstractBackgroundStreptomycesis a highly diverse genus known for the production of secondary or specialized metabolites with a wide range of applications in the medical and agricultural industries. Several thousand complete or nearly-completeStreptomycesgenome sequences are now available, affording the opportunity to deeply investigate the biosynthetic potential within these organisms and to advance natural product discovery initiatives.ResultWe performed pangenome analysis on 2,371Streptomycesgenomes, including approximately 1,200 complete assemblies. Employing a data-driven approach based on genome similarities, theStreptomycesgenus was classified into 7 primary and 42 secondary MASH-clusters, forming the basis for a comprehensive pangenome mining. A refined workflow for grouping biosynthetic gene clusters (BGCs) redefined their diversity across different MASH-clusters. This workflow also reassigned 2,729 known BGC families to only 440 families, a reduction caused by inaccuracies in BGC boundary detections. When the genomic location of BGCs is included in the analysis, a conserved genomic structure (synteny) among BGCs becomes apparent within species and MASH-clusters. This synteny suggests that vertical inheritance is a major factor in the acquisition of new BGCs.ConclusionOur analysis of a genomic dataset at a scale of thousands of genomes refined predictions of BGC diversity using MASH-clusters as a basis for pangenome analysis. The observed conservation in the order of BGCs’ genomic locations showed that the BGCs are vertically inherited. The presented workflow and the in-depth analysis pave the way for large-scale pangenome investigations and enhance our understanding of the biosynthetic potential of theStreptomycesgenus.
Allelic DNA synthesis followed by template switching underlies BRCA1-linked tandem duplication
Authors: Huang Zhi-Cheng , Feng Yi-Li , Liu Qian , Chen Ruo-Dan , Liu Si-Cheng , Wang Meng , Xie An-Yong 
Published: February 2024

AbstractMicrohomology-mediated short tandem duplication (TD) is among specific mutational signatures associated withBRCA1-deficient tumors. Several mechanisms have been proposed for its generation, but may not be applicable in repeat-less regions of the human genome. We thus developed a repeat-less TD reporter and a PCR-based site-specific TD assay to analyze short TDs induced by one-ended DNA double strand breaks (DSBs) converted from DNA nicks inBrca1-deficient cells. We found that short TDs induced by DNA nicks are significantly stimulated inBrca1-deficient cells. Analysis of TD products revealed that the TD formation is partly mediated by template switching of displaced nascent strand after allelic DNA synthesis. This suggests either allelic DNA synthesis or the strand annealing step of allelic break-induced replication might be more easily aborted inBrca1-deficient cells, thus promoting TD. Neither depletion ofRad51orBrca2nor inactivation of the Brca1 coiled-coil domain stimulated nick-induced TD, indicating that RAD51 loading by BRCA1 is dispensable for BRCA1-mediated TD suppression. These results together provide novel insights into the mechanisms underlyingBRCA1-linked TD formation in cancer.
Label-free phenotyping of human microvessel networks
Authors: Rappez Luca , Akinbote Akinola , Cherubini Marta , Uhlmann Virginie , Haase Kristina 
Published: February 2024

AbstractUnderstanding the spatial heterogeneity in blood vessel formation and development is crucial for various biomedical applications. Traditional methods forin-vitromicrovessel segmentation rely on fluorescent labeling, which either interferes with the sample homeostasis, limits the study to a restricted set of precursor cells, or requires sample fixation, thus preventing live measurements. Moreover, these methods often focus on small, cropped images, neglecting global spatial heterogeneity of microvasculature, leading to biased data interpretation. To overcome these limitations, we present VascuMap, a deep-learning-based tool for label-free vessel segmentation and spatial analysis. VascuMap enables a comprehensive examination of entire vessel networks, capturing both morphological and topological features across the full vascular bed. Our method achieves high segmentation accuracy, comparable to the state-of-the-art fluorescence-based models. VascuMap’s capabilities extend to characterizing vasculature generated from label-free patient-derived samples, a vital step towards personalized medicine. Its compatibility with widefield label-free microscopy also accelerates sample acquisition, making it ideal for high-throughput systems crucial for drug toxicity and safety screens.
A handle on mass coincidence errors inde novosequencing of antibodies by bottom-up proteomics
Authors: Schulte Douwe , Snijder Joost 
Published: February 2024

AbstractAntibody sequences can be determined at 99% accuracy directly from the polypeptide product using bottom-up proteomics techniques. This circumvents the need to isolate the antibody-producing B-cell clone and enables reverse engineering of monoclonal antibodies from lost hybridoma cell lines, as well as the secreted protein in bodily fluid. Sequencing accuracy at the peptide level is limited by common mass coincidences of isobaric residues like leucine/isoleucine, but also by incomplete fragmentation spectra in which the order of two or more residues remains ambiguous due to lacking fragment ions for the intermediate positions. Likewise, different combinations of amino acids, of potentially different length, can also coincide to the same mass (e.g. GG=N, GA=Qetc.). Here we present several updates to Stitch (v1.5), which performs template-based assembly ofde novopeptide reads to reconstruct antibody sequences. This version introduces a mass-based alignment algorithm that explicitly accounts for mass coincidence errors. In addition, it incorporates a postprocessing procedure to assign I/L residues based on secondary fragments (satellite ions,i.e. w-ions). Moreover, evidence for sequence assignments can now be directly evaluated with the addition of an integrated spectrum viewer. This version of Stitch also allows input data from a wider selection ofde novopeptide sequencing algorithms, now including Casanovo, PEAKS, Novor.Cloud, pNovo, and MaxNovo, in addition to flat text and FASTA. Combined, these changes make Stitch compatible with a larger range of data processing pipelines and improve its tolerance to peptide-level sequencing errors.
Genomic 8-oxoguanine modulates gene transcription independent of its repair by DNA glycosylases OGG1 and MUTYH
Authors: Obermann Tobias , Sakshaug Teri , Kanagaraj Vishnu Vignesh , Abentung Andreas , Sarno Antonio , Bjørås Magnar , Scheffler Katja 
Published: February 2024

ABSTRACT8-oxo-7,8-dihydroguanine (OG) is one of the most abundant oxidative lesions in the genome and associated with genome instability. Its mutagenic potential is counteracted by a concerted action of 8-oxoguanine DNA glycosylase (OGG1) and mutY homolog DNA glycosylase (MUTYH). It has been suggested that OG and its repair has epigenetic-like properties and mediates transcription, but genome-wide evidence of this interdependence is lacking. Here, we applied an improved OG-sequencing approach reducing artificial background oxidation and RNA-sequencing to correlate genome-wide distribution of OG with gene transcription in OGG1 and/or MUTYH-deficient cells. Our data identified moderate enrichment of OG in the genome that is mainly dependent on the genomic context and not affected by DNA glycosylase-initiated repair. Interestingly, no association was found between genomic OG deposition and gene expression changes upon loss of OGG1 and MUTYH. Regardless of DNA glycosylase activity, OG in promoter regions correlated with expression of genes related to metabolic processes and damage response pathways indicating that OG functions as a cellular stress sensor to regulate transcription. Our work provides novel insights into the mechanism underlying transcriptional regulation by OG and DNA glycosylases OGG1 and MUTYH and suggests that oxidative DNA damage accumulation and its repair utilize different pathways.
Communication with Surprise – Computational Principles of Goal Signaling in Novel Human Interactions
Authors: Buidze Tatia , Sommer Tobias , Zhao Ke , Fu Xiaolan , Gläscher Jan 
Published: February 2024

AbstractCommunication, often grounded in shared expectations, faces challenges without common linguistic backgrounds. Our study explores how people instinctively turn to the fundamental principles of the physical world to overcome communication barriers. Specifically, through the Tacit Communication Game, we investigate how participants develop novel strategies for conveying messages without relying on common linguistic signals. We developed a new computational model built from the principle of expectancy violations of a set of common universal priors derived from movement kinetics. The model closely resembles the Sender’s messages, with its core variable – the information-theoretic surprise – explaining the Receiver’s physiological and neural responses. This is evidenced by a significant correlation with the pupil diameter, indicating cognitive effort, and neural activity in brain areas related to expectancy violations. This work highlights the adaptability of human communication, showing how surprise can be a powerful tool in forming new communicative strategies without relying on common language.