bluuebunny/crossref_metadata_2025_split huggingface dataset:
Confusions regarding stochastic fluctuations and accumulators in spontaneous movements
Authors: Bogler Carsten , Grujičić Bojana , Haynes John-Dylan 
Published: June 2021

ABSTRACTExperiments on choice-predictive brain signals have played an important role in the debate on free will. In a seminal study, Benjamin Libet and colleagues found that a negative-going EEG signal, the readiness potential (RP), can be observed over motor-related brain regions hundreds of ms before the retrospectively reported time of the conscious decision to move. If the onset of the readiness potential is taken as an indicator of the “brain’s decision to move” this could mean that this decision to move is made early, by unconscious brain activity, rather than later, at the time when the subject believes to have decided. However, an alternative kind of interpretation, involving ongoing stochastic fluctuations, has recently been brought to light. One such model, the stochastic decision model (SDM), takes its inspiration from accumulator models of perceptual decision making. It suggests that the RP originates from an accumulation of ongoing stochastic fluctuations. In this view the decision happens only at a much later stage when an accumulated noisy signal (plus imperative) reaches a threshold. Here we clarify a number of confusions regarding both the evidence for the stochastic decision model as well as the interpretation that it offers. We will explore several points that we feel are in need of clarification:(a)that the empirical evidence for the role of stochastic fluctuations is so far only indirect;(b)that the relevance of evidence from animal studies is unclear;(c)that a model that is deterministic during the accumulation stage can explain the data in a similar way;(d)that the primary focus in the literature has been on the role of random fluctuations whereas the deterministic aspects of the model have been largely ignored;(e)that contrary to the original interpretation the deterministic component of the model is the dominant input into the accumulator;(f)that there is confusion regarding the role of “imperative” and “evidence” in the SDM and its link to perceptual decision making; and finally(g)as with other stochastic accumulator processes the question of whether the decision happens early or late depends on the nature of the noise fluctuations, specifically, whether they reflect “absolute” or “epistemic” randomness. Our aim is not to rehabilitate the role of the RP in the free will debate. Rather we aim to address some confusions regarding the evidence for accumulators playing a role in these preparatory brain processes.
The biaxial mechanics of thermally denaturing skin - Part II: Modeling
Authors: Rausch Manuel , Meador William D. , Tubon John Toaquiza , Moreno-Flores Omar , Tepole Adrian Buganza 
Published: June 2021

AbstractUnderstanding the response of skin to superphysiological temperatures is critical to the diagnosis and prognosis of thermal injuries, and to the development of temperature-based medical therapeutics. Unfortunately, this understanding has been hindered by our incomplete knowledge about the nonlinear coupling between skin temperature and its mechanics. In Part I of this study we experimentally demonstrated a complex interdependence of time, temperature, direction, and load in skin’s response to superphysiological temperatures. In Part II of our study, we test two different models of skin’s thermo-mechanics to explain our observations. In both models we assume that skin’s response to superphysiological temperatures is governed by the denaturation of its highly collageneous microstructure. Thus, we capture skin’s native mechanics via a microstructurally-motivated strain energy function which includes probability distributions for collagen fiber orientation and waviness. In the first model, we capture skin’s response to superphysiological temperatures as a transition between two states that link the kinetics of collagen fiber denaturation to fiber coiling and to the transformation of each fiber’s constitutive behavior from purely elastic to viscoelastic. In the second model, we capture skin’s response to super-physiological temperatures instead via three states in which a sequence of two reactions link the kinetics of collagen fiber denaturation to fiber coiling, followed by a state of fiber damage. Given the success of both models in qualitatively capturing our observations, we expect that our work will provide guidance for future experiments that could probe each model’s assumptions toward a better understanding of skin’s coupled thermo-mechanics and that our work will be used to guide the engineering design of heat treatment therapies.
Human magnetic field registration capability using low-field magnetic sensors
Authors: Bricina Natalija , Dehtjars Jurijs , Jašina Ksenija , Sorokins Hermanis 
Published: June 2021

AbstractThe aim of the study was to find out whether it is possible to detect the human magnetic field without shielding using sensors. For this, an experiment “the possibility of detecting the human magnetic field using sensors” was conducted. During the experiment it was found that with the help of a low-field magnetic detector it is possible to register a person’s magnetic field, which is changing if there is a change in a heart rate.During the study, a device for recording the magnetic field of a human was assembled, a methodology for obtaining data was developed, a description of the materials and equipment used was provided. In accordance with the described methods of data collection, measurements of human magnetic field with and without load were made. The data obtained during the study were processed and the results were displayed. Based on the obtained results, an analysis was carried out, conclusions were drawn and recommendations for subsequent studies were indicated. As a result, the possibility of detecting a human’s magnetic field using sensors was first studied.
Exogenous extracellular matrix proteins decrease cardiac fibroblast activation in stiffening microenvironment through CAPG
Authors: Wang Xinming , Pierre Valinteshley , Liu Chao , Senapati Subhadip , Park Paul S.-H. , Senyo Samuel E. 
Published: June 2021

AbstractControlling fibrosis is an essential part of regenerating the post-ischemic heart. In the post-ischemic heart, fibroblasts differentiate to myofibroblasts that produce collagen-rich matrix to physically stabilize the infarct area. Infarct models in adult mice result in permanent scarring unlike newborn animals which fully regenerate. Decellularized extracellular matrix (dECM) hydrogels derived from early-aged hearts have been shown to be a transplantable therapy that preserves heart function and stimulates cardiomyocyte proliferation and vascularization. In this study, we investigate the anti-fibrotic effects of injectable dECM hydrogels in a cardiac explant model in the context of age-associated tissue compliance. Treatments with adult and fetal dECM hydrogels were tested for molecular effects on cardiac fibroblast activation and fibrosis. Altered sensitivity of fibroblasts to the mechanosignaling of the remodeling microenvironment was evaluated by manipulating the native extracellular matrix in explants and also with elastomeric substrates in the presence of dECM hydrogels. The injectable fetal dECM hydrogel treatment decreases fibroblast activation and contractility and lowers the stiffness-mediated increases in fibroblast activation observed in stiffened explants. The anti-fibrotic effect of dECM hydrogel is most observable at highest stiffness. Experiments with primary cells on elastomeric substrates with dECM treatment support this phenomenon. Transcriptome analysis indicated that dECM hydrogels affect cytoskeleton related signaling including Macrophage capping protein (CAPG) and Leupaxin (LPXN). CAPG was down-regulated by the fetal dECM hydrogel. LPXN expression was decreased by stiffening the explants; however, this effect was reversed by dECM hydrogel treatment. Pharmacological disruption of cytoskeleton polymerization lowered fibroblast activation and CAPG levels. Knocking down CAPG expression with siRNA inhibited fibroblast activation and collagen deposition. Collectively, fibroblast activation is dependent on cooperative action of extracellular molecular signals and mechanosignaling by cytoskeletal integrity.
Neutralization against B.1.351 and B.1.617.2 with sera of COVID-19 recovered cases and vaccinees of BBV152
Authors: Yadav Pragya D. , Sapkal Gajanan N. , Ella Raches , Sahay Rima R. , Nyayanit Dimpal A , Patil Deepak Y. , Deshpande Gururaj , Shete Anita M. , Gupta Nivedita , Mohan V. Krishna , Abraham Priya , Panda Samiran , Bhargava Balram 
Published: June 2021

AbstractRecently, multiple SARS-CoV-2 variants have been detected across the globe. The recent emergence of B.1.617 lineage has created serious public health problem in India. The high transmissibility was observed with this lineage which has led to daily increase in the number of SARS-CoV-2 infections. Apparently, the sub-lineage B.1.617.2 has slowly dominated the other variants including B1617.1, B.617.3 and B.1.1.7. With this, World Health Organization has described B.1.617.2 as variant of concern. Besides this, variant of concern B.1.351 has been also reported from India, known to showreducedefficacyfor many approved vaccines. With the increasing threat of the SARS-CoV-2 variants, it is imperative to assess the efficacy of the currently available vaccines against these variants. Here, we have evaluated the neutralization potential of sera collected from COVID-19 recovered cases (n=20) and vaccinees with two doses of BBV152 (n=17) against B.1.351 and B.1.617.2 compared to the prototype B.1 (D614G) variant.The finding of the study demonstrated a reduction in neutralization titers with sera of COVID-19 recovered cases(3.3-fold and 4.6-fold) and BBV152 vaccinees (3. 0 and 2.7 fold) against B.1.351 and B.1.617.2 respectively.Although, there is reduction in neutralization titer, the whole-virion inactivated SARS-CoV-2 vaccine (BBV152) demonstrates protective response against VOC B.1351 and B.1.617.2.
Dice-XMBD: Deep learning-based cell segmentation for imaging mass cytometry
Authors: Xiao Xu , Qiao Ying , Jiao Yudi , Fu Na , Yang Wenxian , Wang Liansheng , Yu Rongshan , Han Jiahuai 
Published: June 2021

AbstractHighly multiplexed imaging technology is a powerful tool to facilitate understanding cells composition and interaction in tumor microenvironment at subcellular resolution, which is crucial for both basic research and clinical applications. Imaging mass cytometry (IMC), a multiplex imaging method recently introduced, can measure up to 40 markers simultaneously in one tissue section by using a high-resolution laser with a mass cytometer. However, due to its high resolution and large number of channels, how to process and interpret the image data from IMC remains a key challenge for its further applications. Accurate and reliable single cell segmentation is the first and a critical step to process IMC image data. Unfortunately, existing segmentation pipelines either produce inaccurate cell segmentation results, or require manual annotation which is very time-consuming. Here, we developed Dice-XMBD, a Deep learnIng-based Cell sEgmentation algorithm for tissue multiplexed imaging data. In comparison with other state-of-the-art cell segmentation methods currently used in IMC, Dice-XMBD generates more accurate single cell masks efficiently on IMC images produced with different nuclear, membrane and cytoplasm markers. All codes and datasets are available at https://github.com/xmuyulab/Dice-XMBD.
Genome-wide reconstruction of rediploidization following autopolyploidization across one hundred million years of salmonid evolution
Authors: Gundappa Manu Kumar , To Thu-Hien , Grønvold Lars , Martin Samuel A.M. , Lien Sigbjørn , Geist Juergen , Hazlerigg David , Sandve Simen R. , Macqueen Daniel J. 
Published: June 2021

AbstractThe long-term evolutionary impacts of whole genome duplication (WGD) are strongly influenced by the ensuing rediploidization process. Following autopolyploidization, rediploidization involves a transition from tetraploid to diploid meiotic pairing, allowing duplicated genes (ohnologues) to diverge genetically and functionally. Our understanding of autopolyploid rediploidization has been informed by a WGD event ancestral to salmonid fishes, where large genomic regions are characterized by temporally delayed rediploidization, allowing lineage-specific ohnologue sequence divergence in the major salmonid clades. Here, we investigate the long-term outcomes of autopolyploid rediploidization at genome-wide resolution, exploiting a recent ‘explosion’ of salmonid genome assemblies, including a new genome sequence for the huchen (Hucho hucho). We developed a genome alignment approach to capture duplicated regions across multiple species, allowing us to create 121,864 phylogenetic trees describing ohnologue divergence across salmonid evolution. Using molecular clock analysis, we show that 61% of the ancestral salmonid genome experienced an initial ‘wave’ of rediploidization in the late Cretaceous (85-106 Mya). This was followed by a period of relative genomic stasis lasting 17-39 My, where much of the genome remained in a tetraploid state. A second rediploidization wave began in the early Eocene and proceeded alongside species diversification, generating predictable patterns of lineage-specific ohnologue divergence, scaling in complexity with the number of speciation events. Finally, using gene set enrichment, gene expression, and codon-based selection analyses, we provide insights into potential functional outcomes of delayed rediploidization. Overall, this study enhances our understanding of delayed autopolyploid rediploidization and has broad implications for future studies of WGD events.
Reporting amyloid beta levelsviabioluminescence imaging with amyloid reservoirs in Alzheimer’s disease models
Authors: Yang Jing , Ding Weihua , Zhu Biyue , Zhen Sherri , Kuang Shi , Zhang Can , Wang Peng , Yang Fan , Yang Liuyue , Yin Wei , Tanzi Rudolph E. , Shen Shiqian , Ran Chongzhao 
Published: June 2021

AbstractBioluminescence imaging has changed daily practice in preclinical research of cancers and other diseases in the last decades; however, it has been rarely applied in preclinical research of Alzheimer’s disease (AD). In this report, we demonstrated that bioluminescence imaging could be used to report the levels of amyloid beta (Aβ) species in vivo. We hypothesized that AkaLumine, a newly discovered substrate for luciferase, could bind to Aβ aggregates and plaques. We further speculated that the Aβ species have the reservoir capacity to sequester and release AkaLumine to control the bioluminescence intensity, which could be used to report the levels of Aβs. Our hypotheses have been validatedvia in vitrosolution tests, mimic studies with brain tissues and mice, two-photon imaging with AD mice, andin vivobioluminescence imaging using transgenic AD mice that were virally transduced with aka Luciferase (AkaLuc), a new luciferase that generates bioluminescence in the near infrared window. As expected, compared to the control group, we observed that the Aβ group showed lower bioluminescence intensity due to AkaLumine sequestering at early time points, while higher intensity due to AkaLumine releasing at later time points. Lastly, we demonstrated that this method could be used to monitor AD progression and therapeutic effectiveness of avagacestat, a well-studied gamma-secretase inhibitor. Importantly, a good correlation (R2= 0.81) was established between in vivo bioluminescence signals and Aβ burdens of the tested AD mice. We believe that our approach can be easily implemented into daily imaging experiments and has tremendous potential to change daily practice of preclinical AD research.
Inverse Lansing effect: maternal age and provisioning affecting daughters’ longevity and male offspring production
Authors: Anderson Cora E. , Homa Camille , Jonas-Closs Rachael A , Peshkin Leonid , Kirschner Marc W. , Yampolsky Lev Y. 
Published: June 2021

AbstractMaternal age effects on life history of offspring has been demonstrated in a variety of organisms, more often than not offspring of older mothers having lower life expectancy (Lansing effect). However, there is no consensus on how general this phenomenon is and what are the genetic and epigenetic mechanisms behind it. We tested the predictions of Lansing effect in several Daphnia magna clones in and observed a significant genotype-by-maternal age interaction, indicating clone-specific magnitude and direction of the effect of maternal age on daughters’ longevity. We then repeated this experiment with more detailed life-history and offspring provisioning data focusing on 2 clones with contrasting life-histories. One of these clones demonstrating the inverse Lansing effect, with daughters of older mothers living longer than those of young mothers. Individuals from a single-generation maternal age reversal treatment showed intermediate lifespan. We also report genotype-specific, ambidirectional, and largely fecundity-independent effects of maternal age on daughters’ propensity to produce male offspring, with daughters of older mothers showing higher male production than daughters of younger mothers in the least male-producing clone and vise versa. We tested whether both effects can be explained by either lipid provisioning of embryos by mothers of different age, or by properties of mitochondria transmitted by mothers of different age to their offspring, using rhodamine-123 assay of mitochondrial membrane potential as a measure of mitochondria quality. We show that once lipid provisioning is accounted for, the effects of maternal age on lifespan and male production disappear and that the effect of lipid provisioning itself is clone-dependent, confirming that maternal provisioning sets daughters life history parameters. In the clone showing the inverse Lansing effect we demonstrated that, contrary to the predictions, neonates produced by older mothers were characterized by higher mitochondrial membrane potential in neural tissues than their counterparts born to younger mothers. We conclude that, in at least some genotypes, a reverse Lansing effect is possible, and hypothesize that it may be a result of lower lipid provisioning creating calorically restricted environment during embryonic development.
FXR inhibition reduces ACE2 expression, SARS-CoV-2 infection and may improve COVID-19 outcome
Authors: Brevini Teresa , Maes Mailis , Webb Gwilym J. , Gelson William T. H. , Forrest Sally , Mlcochova Petra , Dillon Scott , Varankar Sagar , Darvish-Damavandi Mahnaz , Mulcahy Victoria L. , Kuc Rhoda E. , Williams Thomas L. , Galanakis Vasileios , Vila-Gonzalez Marta , Tysoe Olivia C. , Muraro Daniele , Crozier Thomas W. M. , Bargehr Johannes , Sinha Sanjay , Upponi Sara S. , Swift Lisa , Saeb-Parsy Kourosh , Davies Susan E. , Marjot Thomas , Barnes Eleanor , Lohse Ansgar W. , Moon Andrew M. , Sidney Barritt A. , Gupta Ravindra K. , Baker Stephen , Davenport Anthony P. , Corbett Gareth , Buczacki Simon J. A. , Lee Joo-Hyeon , Gibbs Paul , Butler Andrew J. , Watson Christopher J. E. , Mells George F. , Dougan Gordon , Vallier Ludovic , Sampaziotis Fotios 
Published: June 2021

AbstractPrevention of SARS-CoV-2 entry in cells through the modulation of viral host receptors, such as ACE2, could represent a new therapeutic approach complementing vaccination. However, the mechanisms controlling ACE2 expression remain elusive. Here, we identify the farnesoid X receptor (FXR) as a direct regulator of ACE2 transcription in multiple COVID19-affected tissues, including the gastrointestinal and respiratory systems. We demonstrate that FXR antagonists, including the over-the-counter compound z-guggulsterone (ZGG) and the off-patent drug ursodeoxycholic acid (UDCA), downregulate ACE2 levels, and reduce susceptibility to SARS-CoV-2 infection in lung, cholangiocyte and gut organoids. We then show that therapeutic levels of UDCA downregulate ACE2 in human organs perfused ex situ and reduce SARS-CoV-2 infection ex vivo. Finally, we perform a retrospective study using registry data and identify a correlation between UDCA treatment and positive clinical outcomes following SARS-CoV-2 infection, including hospitalisation, ICU admission and death. In conclusion, we identify a novel function of FXR in controlling ACE2 expression and provide evidence that this approach could be beneficial for reducing SARS-CoV-2 infection, thereby paving the road for future clinical trials.
ProCanBio: a database of manually curated biomarkers for Prostate Cancer
Authors: Sapra Dikscha , Kaur Harpreet , Dhall Anjali , Raghava Gajendra P. S. 
Published: June 2021

AbstractBackgroundProstate Cancer is the second lethal malignancy in men worldwide. In the past, numerous research groups investigated the omics profiles of patients and scrutinized biomarkers for the diagnosis and prognosis of prostate cancer. However, information related to the biomarkers is widely scattered across numerous resources in complex textual format, which poses hindrance to understand the tumorigenesis of this malignancy and scrutinization of robust signature. To the best of authors’ knowledge, there is no resource that can consolidate the information contained in all the published literature.ResultsHere, we present ProCanBio, a manually curated database that maintains detailed data on 2053 entries of potential prostate cancer biomarkers obtained from 412 publications in user friendly tabular format. Among them, 766 protein-based, 488 RNA-based, 157 genomic mutations, 261 miRNA-based, and 122 are metabolites-based biomarkers. To explore the information in the resource, a web-based interactive platform was developed with searching, and browsing facilities. ProCanBio is freely available and is compatible with most web browsers and devices. Eventually, we anticipated this resource will be highly useful for the research community involved in the area of prostate malignancy.AvailabilityProCanBio is available at: https://webs.iiitd.edu.in/raghava/procanbio/
Enrichment analysis of GWAS data in autoimmunity delineates the multiple sclerosis-Epstein Barr virus association
Authors: Mechelli Rosella , Umeton Renato , Rinaldi Virginia , Bellucci Gianmarco , Bigi Rachele , Angelini Daniela F. , Guerrera Gisella , Srinivasan Sundararajan , Romano Silvia , Buscarinu Maria Chiara , Pizzolato Umeton Raffaella , Anastasiadou Eleni , Trivedi Pankaj , Fornasiero Arianna , Ferraldeschi Michela ,   IMSGC and WTCCC2, Centonze Diego , Uccelli Antonio , Di Silvestre Dario , Mauri Pier Luigi , de Candia Paola , Matarese Giuseppe , D’Alfonso Sandra , Battistini Luca , Farina Cinthia , Magliozzi Roberta , Reynolds Richard , Salvetti Marco , Ristori Giovanni 
Published: June 2021

SUMMARYWe exploited genetic information to assess non-genetic influences in autoimmunity. We isolated gene modules whose products physically interact with environmental exposures related to autoimmunity, and analyzed their nominal statistical evidence of association with autoimmune and non-autoimmune diseases in genome-wide association studies (GWAS) data. Epstein Barr virus (EBV) and other Herpesviruses interactomes emerged as specifically associated with multiple sclerosis (MS), possibly under common regulatory mechanisms. Analyses of MS blood and brain transcriptomes, cytofluorimetric studies of endogenous EBV-infected lymphoblastoid lines, and lesion immunohistochemistry, confirmed a dysregulation of MS-associated EBV interactors, suggesting their contribution to CD40 signaling alterations in MS. These interactors resulted enriched in modules from inherited axonopathies-causing genes, supporting a link between EBV and neurodegeneration in MS, in accord with the observed transcriptomic dysregulations in MS brains. They were also enriched with top-ranked pharmaceutical targets prioritized on a genetic basis. This study delineates a disease-specific influence of herpesviruses on MS biology.