bluuebunny/crossref_metadata_2025_split huggingface dataset:
An atlas of spider development at single-cell resolution provides new insights into arthropod embryogenesis
Authors: Leite Daniel J. , Schönauer Anna , Blakeley Grace , Harper Amber , Garcia-Castro Helena , Baudouin-Gonzalez Luis , Wang Ruixun , Sarkis Naïra , Nikola Alexander Günther , Koka Venkata Sai Poojitha , Kenny Nathan J. , Turetzek Natascha , Pechmann Matthias , Solana Jordi , McGregor Alistair P. 
Published: June 2022

AbstractSpiders are a diverse order of chelicerates that diverged from other arthropods over 500 million years ago. Research on spider embryogenesis, particular studies using the common house spiderParasteatoda tepidariorum, has made important contributions to understanding the evolution of animal development, including axis formation, segmentation, and patterning. However, we lack knowledge about the cells that build spider embryos, their gene expression profiles and fate. Single-cell transcriptomic analyses have been revolutionary in describing these complex landscapes of cellular genetics in a range of animals. Therefore, we carried out single-cell RNA sequencing ofP. tepidariorumembryos at stages 7, 8 and 9, which encompass the establishment and patterning of the body plan, and initial differentiation of many tissues and organs. We identified 20 cell clusters, from 18.5k cells, which were marked by many developmental toolkit genes, as well as a plethora of genes not previously investigated. There were differences in the cell cycle transcriptional signatures, suggestive of different proliferation dynamics, which related to distinctions between endodermal and some mesodermal clusters, compared with ectodermal clusters. We found many Hox genes were markers of cell clusters, and Hox gene ohnologs often were present in different clusters. This provided additional evidence of sub- and/or neo-functionalisation of these important developmental genes after the whole genome duplication in the arachnopulmonate ancestor (spiders, scorpions, and allies). We also examined the spatial expression of marker genes for each cluster to generate a comprehensive cell atlas of these embryonic stages. This revealed new insights into the cellular basis and genetic regulation of head patterning, hematopoiesis, limb development, gut development, and posterior segmentation. This atlas will serve as a platform for future analysis of spider cell specification and fate, and studying the evolution of these processes among animals at cellular resolution.
Doing what’s not wanted: conflict in incentives and misallocation of behavioural control lead to drug-seeking despite adverse outcomes
Authors: Mahajan Pranav , Baths Veeky , Gutkin Boris 
Published: June 2022

AbstractDespite being aware of negative consequences and wanting to quit, long-term addicts find it difficult to quit seeking and consuming drugs. This inconsistency between the (often compulsive) behavioural patterns and the explicit knowledge of negative consequences represents a cognitive conflict which is a central characteristic of addiction. Neurobiologically, differential cue-induced activity in distinct striatal subregions, as well as the dopamine connectivity spiraling from ventral striatal regions to the dorsal regions, play critical roles in compulsive drug seeking. The focus of this work is to illustrate the mechanisms that lead to a cognitive conflict and it’s impact on actions taken i.e. addictive choices. We propose an algorithmic model that captures how the action choices that the agent makes when reinforced with drug-rewards become incongruent with the presence of negative consequences that often follow those choices. We advance the understanding of having a decision hierarchy in representing “cognitive control” and how lack of such control at higher-level in the hierarchy could potentially lead to consolidated drug-seeking habits. We further propose a cost-benefit based arbitration scheme, which mediates the allocation of control across different levels of the decision-making hierarchy. Lastly, we discuss how our work on extending a computational model to an algorithmic one, could in turn also helps us improve the understanding of how drugs hijack the dopamine-spiralling circuit at an implementation level.
A plausible identifiable model of the canonical NF-κB signaling pathway
Authors: Jaruszewicz-Błońska Joanna , Kosiuk Ilona , Prus Wiktor , Lipniacki Tomasz 
Published: June 2022

AbstractAn overwhelming majority of mathematical models of regulatory pathways, including intensively studied NF-κB pathway, remains non-identifiable meaning that their parameters may not be determined by existing data. The existing NF-κB models that are capable to reproduce experimental data, contain non-identifiable parameters, while simplified models with a smaller number of parameters exhibit dynamics that significantly differs from that observed in experiments. Here, we reduce an existing model of the canonical NF-κB pathway by decreasing the number of equations from 15 to 6 in a way that the resulting model exhibits dynamics closely following that of the original model, both for the nominal and the randomly selected parameters. We carried out the sensitivity-based linear analysis and Monte Carlo-based analysis to demonstrate that the resulting model is structurally and practically identifiable based on a simple TNF stimulation protocol in which 5 model variables are measured. The reduced model is capable to reproduce different types of responses characteristic to regulatory motives controlled by negative feedback loops: nearly-perfect adaptation, damped and sustained oscillations. It can serve as a building block of more comprehensive models of immune responses and cancer, where NF-κB plays a decisive role. Our approach, although may not be automatically generalized, suggests that other regulatory pathways models can be transformed to identifiable, while retaining their dynamical features.
Regulation of Aortic Morphogenesis and VE-Cadherin Dynamics by VEGF
Authors: Jadon Julian , Yelin Ronit , Arraf Alaa A. , Asleh Manar Abboud , Zaher Mira , Schultheiss Thomas M. 
Published: June 2022

AbstractIn amniote vertebrates, the definitive dorsal aorta is formed by the side-to-side fusion of two primordial aortic endothelial tubes. Formation of the definitive dorsal aorta requires extensive cellular migrations and rearrangements of the primordial tubes in order to generate a single fused vessel located at the embryonic ventral midline. This study examines the role of VEGF signaling in the generation of the definitive dorsal aorta. Through gain- and loss-of-function studies in vivo in the chick embryo, we document a requirement for VEGF signaling in growth and migration of the paired primordia, and identify a developmental window in which aorta development is particularly sensitive to VEGF signaling. We also find that VEGF signaling regulates the intracellular distribution between membrane and cytoplasm of the cell-cell adhesion molecule VE-Cadherin in aortic endothelial cells in vivo, suggesting a possible mechanism for how VEGF regulates aortic endothelial cell dynamics during the fusion process.
Image Downsampling Expedited Adaptive Least-squares (IDEAL) fitting improves intravoxel incoherent motion (IVIM) analysis in the human kidney
Authors: Stabinska Julia , Zöllner Helge J. , Thiel Thomas , Wittsack Hans-Jörg , Ljimani Alexandra 
Published: June 2022

ABSTRACTPurposeTo improve the reliability of intravoxel incoherent motion model (IVIM) parameter estimation for the diffusion-weighted imaging in the kidney using a novel Image Downsampling Expedited Adaptive Least-squares (IDEAL) approach.MethodsThe robustness of IDEAL was investigated using simulated diffusion-weighted MRI data corrupted with different levels of Rician noise. Subsequently, the performance of the proposed method was tested by fitting bi- and triexponential IVIM model to in vivo renal DWI data acquired on a clinical 3 Tesla MRI scanner and compared to conventional approaches (Fixed D* and Segmented fitting).ResultsThe numerical simulations demonstrated that the IDEAL algorithm provides robust estimates of the IVIM parameters in the presence of noise as indicated by relatively low absolute percentage bias (sMdPB [%]) and normalized root-mean-square error (RMSE [%]). The analysis of the in vivo data showed that the IDEAL-based IVIM parameter maps were less noisy and more visually appealing than those obtained using the Fixed D* and Segmented methods. Further, the use of IDEAL for the triexponential IVIM modelling resulted in reduced cortical and medullary coefficients of variation (CVs) for all IVIM parameters when compared with Fixed D*, reflecting greater accuracy of this method.ConclusionThe proposed fitting algorithm yields more robust IVIM parameter estimates and is less susceptible to poor SNR than the conventional fitting approaches. Thus, the IDEAL approach has the potential to improve the reliability of renal DW-MRI analysis for clinical applications.
Scale-free and oscillatory spectral measures of sleep stages in humans
Authors: Schneider Bence , Szalárdy Orsolya , Ujma Péter P. , Simor Péter , Gombos Ferenc , Kovács Ilona , Dresler Martin , Bódizs Róbert 
Published: June 2022

ABSTRACTPower spectra of sleep electroencephalograms (EEG) comprise two main components: a decaying power-law corresponding to the aperiodic neural background activity, and spectral peaks present due to neural oscillations.’Traditional’ band-based spectral methods ignore this fundamental structure of the EEG spectra and thus are susceptible to misrepresenting the underlying phenomena. A fitting method that attempts to separate and parameterize the aperiodic and periodic spectral components called ‘fitting oscillations & one over f’ (FOOOF) was applied to a set of annotated whole-night sleep EEG recordings of 251 subjects from a wide age range (4-69 years). Most of the extracted parameters exhibited sleep stage sensitivity; significant main effects and interactions of sleep stage, age, sex, and brain region were found. The spectral slope (describing the steepness of the aperiodic component) showed especially large and consistent variability between sleep stages (and low variability between subjects), making it a candidate indicator of sleep states. The limitations and arisen problems of the FOOOF method are also discussed, possible solutions for some of them are suggested.
Intraoperative Spinal Cord Stimulation Mitigates Pain after Spine Surgery in Mice
Authors: Yamamoto Satoshi , Duong Alexander , Kim Alex , Hu Chengrui , Wiemers Blaine , Wang Jigong , Chung Jin Mo , La Jun-Ho 
Published: June 2022

AbstractBackgroundManaging postoperative pain after spine surgery is challenging, and up to 40% of operated patients develop failed back surgery syndrome (FBSS) resulting in intractable back and/or leg pain. While spinal cord stimulation (SCS) has been shown to effectively alleviate such chronic pain, it is unknown if intraoperative SCS can mitigate the development of central sensitization that potentially causes intense postoperative pain and FBSS after spine surgery.MethodsAs an experimental spine surgery, unilateral T13 laminectomy was performed in mice to expose the dorsal part of L4-5 spinal segments that receive sensory inputs from the hind limb. After the laminectomy, a group of mice received intraoperative SCS epidurally applied to the exposed side of the dorsal part of the spinal cord for an hour under anesthesia before closing the surgical wounds. Secondary mechanical hypersensitivity, a behavioral manifestation of central sensitization, was measured in hind paws using von Frey assay one day before and at predetermined times after surgery. In addition, because von Frey assay is a nocifensive reflex-based analysis that primarily assesses the sensory-discriminative domain of pain, we also performed a conflict avoidance test to capture the affective-motivational domain of pain at selected timepoints post-laminectomy.ResultsMice that underwent unilateral T13 laminectomy developed mechanical hypersensitivity in both hind paws, which gradually resolved in 1-2 weeks. The extent of the hypersensitivity was significantly less in the contralateral hind paw (relative to the laminectomy) than in the ipsilateral hind paw only in females.Intraoperative SCS applied to the exposed side of the dorsal -spinal cord significantly inhibited the development of hind paw mechanical hypersensitivity only in the SCS-applied side. When paws were mechanically stimulated in their preferred place to present a conflict between pain/discomfort and natural preference, mice avoided the conflict after laminectomy, spending less time in the place than before the surgery. However, mice treated with intraoperative SCS after laminectomy did not avoid the conflict.ConclusionThese results demonstrate that spine surgery for unilateral laminectomy induces central sensitization that results in postoperative pain hypersensitivity.Intraoperative SCS after laminectomy can mitigate the development of this hypersensitivity in the SCS-applied side.
coda4microbiome: compositional data analysis for microbiome studies
Authors: Calle M.Luz , Susin Antoni 
Published: June 2022

AbstractMotivationOne of the main challenges of microbiome analysis is its compositional nature that if ig-nored can lead to spurious results. This is especially critical when dealing with microbiome variable selection since classical differential abundance tests are known to provide large false positive rates.ResultsWe developed coda4microbiome, a new R package for analyzing microbiome data within the Compositional Data Analysis (CoDA) framework in both, cross-sectional and longitudinal studies. The core functions of the library are aimed at the identification of microbial signatures and involve variable selection in generalized linear models with compositional covariates. All algorithms are accompanied by meaningful graphical representations that allow a better interpretation of the results.Availabilitycoda4microbiome is implemented as an R package and is available at CRANhttps://cran.r-project.org/web/packages/coda4microbiome/index.html.Contactmalu.calle@uvic.catSupplementary informationcoda4microbiome project website:https://malucalle.github.io/coda4mi-crobiome/.
Annotation of structural variants with reported allele frequencies and related metrics from multiple datasets using SVAFotate
Authors: Nicholas Thomas J. , Cormier Michael J. , Quinlan Aaron R. 
Published: June 2022

AbstractBackgroundIdentification of impactful genetic variants from DNA sequencing data relies on increasingly detailed filtering strategies to isolate the small subset of variants that are more likely to underlie a disease phenotype. Datasets reflecting population allele frequencies of different types of variants have been demonstrated as powerful filtering tools, especially in the context of rare disease analysis. While such population-scale allele frequency datasets now exist for structural variants (SVs), it remains a challenge to match SV calls between multiple datasets and thereby correctly estimate the population allele frequency of a putative SV.ResultsWe introduce SVAFotate, a software tool for SV matching that enables the annotation of SVs with variant allele frequency and related information. These annotations are derived from known SV datasets which are incorporated by SVAFotate. As a result, VCF files annotated by SVAFotate offer a variety of annotations to aid in the stratification of SVs as common or rare in the broader human population.ConclusionsHere we demonstrate the use of SVAFotate in the classification of SVs with regards to their population frequency and illustrate how annotations provided by SVAFotate can be used to filter and prioritize SVs. Lastly, we detail how best to utilize these SV annotations in the analysis of genetic variation in studies of rare disease.
Pulsed transistor operation enables miniaturization of electrochemical aptamer–based sensors
Authors: Bidinger Sophia L. , Keene Scott T. , Han Sanggil , Plaxco Kevin W. , Malliaras George G. , Hasan Tawfique 
Published: June 2022

AbstractBy simultaneously transducing and amplifying, transistors offer advantages over simpler, electrode-based transducers in electrochemical biosensors. However, transistor-based biosensors typically use static (i.e., DC) operation modes that are poorly suited for sensor architectures relying on the modulation of charge transfer kinetics to signal analyte binding. Thus motivated, here we translate the AC “pulsed potential” approach typically used with electrochemical aptamer-based sensor to an organic electrochemical transistor (OECT). Specifically, by applying a linearly sweeping square-wave potential to an aptamer-functionalized gate electrode, we produce current modulation across the transistor channel two orders of magnitude larger than seen for the equivalent, electrode-based biosensor. Critically, the resulting amplification is scalable, such that there is no signal loss with OECT miniaturization. The pulsed transistor operation demonstrated here could be applied generally to sensors relying on kinetics-based signaling, expanding opportunities for non-invasive and high spatial resolution biosensing.
Nitric oxide S-nitrosylates CSF1R to augment the action of CSF1R inhibition against castration resistant prostate cancer
Authors: Kuchakulla Manish , Firdaus Fakiha , Qureshi Rehana , Soni Yash , Van Booven Derek J , Shah Khushi , Dulce Raul Ariel , Masterson Thomas , Rosete Omar Joel , Hare Joshua M. , Ramasamy Ranjith , Arora Himanshu 
Published: June 2022

AbstractDuring progression of prostate cancer, sustained oxidative overload in cancer cells potentiates the overall tumor microenvironment (TME). Targeting the TME using colony-stimulating factor 1 receptor (CSF1R) inhibition is a promising therapy for castration-resistant prostate cancer (CRPC). However, the therapeutic response to sustained CSF1R blockade therapy (CSF1Ri) is limited as a monotherapy. We postulated that one of the causative agents for reduced efficacy of CSF1Ri and increased oxidation in CRPC is endothelial nitric oxide syntheses (eNOS). Results showed that in high grade PCa human specimens, eNOS is positively correlated with CSF1-CSF1R signaling and remains in an un-coupled state. The uncoupling disables eNOS to generate sufficient Nitric oxide (NO) that are required for inducing effective S-nitrosylation of CSF1R molecule at specific cysteine sites (Cys 224, Cys 278 and Cys 830). Importantly, we found that S-nitrosylation of CSF1R molecule at Cys 224, Cys 278 and Cys 830 sites is necessary for effective inhibition of tumor promoting cytokines (which are downstream of CSF1-CSF1R signaling) by CSF1R blockade. In this context, we studied if exogenous NO treatment could rescue the side effects of eNOS uncoupling. Results showed that exogenous NO treatment (using S-nitrosoglutathione (GSNO)) is effective in not only inducing S-Nitrosylation of CSF1R molecule, but it helps in rescuing the excess oxidation in tumor regions, reducing overall tumor burden, suppresses the tumor promoting cytokines which are ineffectively suppressed by CSF1R blockade. Together these results postulated that NO therapy could act as an effective combinatorial partner with CSF1R blockade against CRPC. In this context, results demonstrated that exogenous NO treatment successfully augment the anti-tumor ability of CSF1Ri in murine models of CRPC. Importantly, the overall tumor reduction was most effective in NO-CSF1Ri therapy compared to NO or CSF1Ri mono therapies. Moreover, Immunophenotyping of tumor grafts showed that the NO-CSF1Ri combination significantly decreased intratumoral percentage of anti-inflammatory macrophages, myeloid derived progenitor cells and increased the percentage of pro-inflammatory macrophages, cytotoxic T lymphocytes, and effector T cells respectively. Together, our study suggests that the NO-CSF1Ri combination has the potential to act as a therapeutic agent that restore control over TME and improve the outcomes of PCa patients.
Longitudinal brain studies in adult zebrafish by MRI
Authors: Hamilton Noémie , Allen Claire , Reynolds Steven 
Published: June 2022

AbstractZebrafish (Danio rerio) has been successfully used for decades in developmental studies and disease modelling. The remarkable intake of zebrafish as a model system is partly due to its transparency during the early weeks of its development, allowing in vivo imaging of cellular and molecular processes. However, this key advantage wears off when tissues become opaque as the animal reaches juvenile and adult stages, rendering access to tissues for live imaging and longitudinal studies difficult. Here we aimed to provide a novel approach to image and assess tissue integrity of adult zebrafish using Magnetic Resonance Imaging (MRI) on live zebrafish suitable for longitudinal studies. We built a 3D-printed life support chamber and designed a protocol-directed sedation regime to recover adult zebrafish post scanning in a 9.4T MRI scanner. Our life support chamber is cheap and easy to create using 3D printing, allowing other groups to copy our template for quick setup. Additionally, we optimised the delivery of contrast agent to enhance brain signals in order to refine current delivery, usually delivered by intravenous in rodents. We show here that immersion in gadolinium was a viable alternative to intraperitoneal injection to reduce T1 relaxation times. This could lead to improved image contrast in adult zebrafish disease models. In conclusion, we provide here a detailed methodology to allow longitudinal studies of brain tissue integrity of adult zebrafish, combining safe and efficient delivery of contrast agent and live MRI. This technique can be used to bridge the gap between in vivo studies and longitudinal brain analysis in adult zebrafish which can be applied to the ever-growing number of adult zebrafish models of ageing and neurodegenerative diseases.
Along-tract quantification of resting-state BOLD hemodynamic response functions in white matter
Authors: Schilling Kurt G , Li Muwei , Rheault Francois , Ding Zhaohua , Anderson Adam W , Kang Hakmook , Landman Bennett A , Gore John C 
Published: June 2022

AbstractDetailed knowledge of the BOLD hemodynamic response function (HRF) is crucial for accurate analysis and interpretation of functional MRI data. Considerable efforts have been made to characterize the HRF in gray matter (GM) but much less is known about BOLD effects in white matter (WM). However, recent reports have demonstrated reliable detection and analyses of WM BOLD signals after stimulation and in a resting state. WM and GM differ in energy requirements and blood flow, so neurovascular couplings may well be different. We aimed to derive a comprehensive characterization of the HRF in WM across a population, including accurate measurements of its shape and its variation along and between WM pathways, using resting-state fMRI acquisitions. Our results show that the HRF is significantly different between WM and GM. Features of the HRF, such as a prominent initial dip, show strong relationships with features of the tissue microstructure derived from diffusion imaging, and these relationships differ between WM and GM, consistent with BOLD signal fluctuations reflecting different energy demands and differences in neurovascular coupling between tissues of different composition. We also show that the HRF varies significantly along WM pathways, and is different between different WM pathways. Thus, much like in GM, changes in flow and/or oxygenation are different for different parts of the WM. These features of the HRF in WM are especially relevant for interpretation of the biophysical basis of BOLD effects in WM.