bluuebunny/crossref_metadata_2025_split huggingface dataset:
Failed remyelination of the non-human primate optic nerve leads to axon degeneration, retinal damages and visual dysfunction
Authors: Sarrazin Nadège , Chavret-Reculon Estelle , Bachelin Corinne , Felfli Mehdi , Arab Rafik , Gilardeau Sophie , Brazhnikova Elena , Dubus Elisabeth , Yaha-Cherif Lydia , Lorenceau Jean , Picaud Serge , Rosolen Serge , Moissonnier Pierre , Pouget Pierre , Baron-Van Evercooren Anne 
Published: January 2022

AbstractWhite matter disorders of the CNS such as MS, lead to failure of nerve conduction and long-lasting neurological disabilities affecting a variety of sensory and motor systems including vision. While most disease-modifying therapies target the immune and inflammatory response, the promotion of remyelination has become a new therapeutic avenue, to prevent neuronal degeneration and promote recovery. Most of these strategies are developed in short-lived rodent models of demyelination, which spontaneously repair and do not reflect the size, organization, and biology of the human CNS. Thus, well-defined non-human primate models are required to efficiently advance therapeutic approaches for patients. Here, we followed the consequence of long-term toxin-induced demyelination of the macaque optic nerve on remyelination and axon preservation, as well as its impact on visual functions. Findings from oculo-motor behavior, ophthalmic examination, electrophysiology, and retinal imaging indicate visual impairment involving the optic nerve and retina. These visual dysfunctions fully correlated at the anatomical level, with sustained optic nerve demyelination, axonal degeneration, and alterations of the inner retinal layers. This non-human primate model of chronic optic nerve demyelination associated with axonal degeneration and visual dysfunction, recapitulates several key features of MS lesions and should be instrumental in providing the missing link to translate emerging repair pro-myelinating/neuroprotective therapies to the clinic for myelin disorders such as MS.Significance StatementPromotion of remyelination has become a new therapeutic avenue, to prevent neuronal degeneration and promote recovery in white matter diseases such as MS. To date most of these strategies are developed in short-lived rodent models of demyelination, which spontaneously repair. Well-defined non-human primate models closer to man would allow to efficiently advance therapeutic approaches. Here we present a non-human primate model of optic nerve demyelination that recapitulates several features of MS lesions. The model leads to failed remyelination, associated with progressive axonal degeneration and visual dysfunction, thus providing the missing link to translate emerging pre-clinical therapies to the clinic for myelin disorders such as MS.
Sex differences in pain-related behaviors and clinical progression of disease in mouse models of visceral pain
Authors: Francis-Malave Adela M. , Gonzalez Santiago Martinez , Pichardo Caren , Wilson Torri D. , Rivera Luis G. , Brinster Lauren R. , Carrasquillo Yarimar 
Published: January 2022

ABSTRACTPrevious studies have reported sex differences in irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) patients, including differences in visceral pain perception. Despite this, sex differences in behavioral manifestations of visceral pain and underlying pathology of the gastrointestinal tract have been largely understudied in preclinical research. In this study, we evaluated potential sex differences in spontaneous visceral nociceptive responses, referred abdominal hypersensitivity, disease progression and bowel pathology in mouse models of acute and persistent colon inflammation. Our experiments show that females exhibit more visceral nociceptive responses and referred abdominal hypersensitivity than males in the context of acute but not persistent colon inflammation. We further demonstrate that, following acute and persistent colon inflammation, visceral pain-related behavioral responses in females and males are distinct, with increases in licking of the abdomen only observed in females and increases in abdominal contractions only seen in males. During persistent colon inflammation, males exhibit worse disease progression than females, which is manifested as worse physical appearance and higher weight loss. However, no measurable sex differences were observed in persistent inflammation-induced bowel pathology, stool consistency or fecal blood. Overall, our findings demonstrate that visceral pain-related behaviors and disease progression in the context of acute and persistent colon inflammation are sex-dependent, highlighting the importance of considering sex as a biological variable in future mechanistic studies of visceral pain as well as in the development of diagnostics and therapeutic options for chronic gastrointestinal diseases.
Engineered cell differentiation and sexual reproduction in probiotic and mating yeasts
Authors: Jensen Emil D. , Deichmann Marcus , Ma Xin , Vilandt Rikke U. , Schiesaro Giovanni , Rojek Marie B. , Lengger Bettina , Eliasson Line , Vento Justin M. , Durmusoglu Deniz , Hovmand Sandie P. , Al’Abri Ibrahim , Zhang Jie , Crook Nathan , Jensen Michael K. 
Published: January 2022

AbstractG protein-coupled receptors (GPCRs) enable cells to sense environmental cues and are indispensable for coordinating vital processes including quorum sensing, proliferation, and sexual reproduction. GPCRs comprise the largest class of cell surface receptors in eukaryotes, and for more than three decades the pheromone-induced mating pathway in baker’s yeast Saccharomyces cerevisiae has served as a model for studying heterologous GPCRs (hGPCRs). Here we report transcriptome profiles following mating pathway activation in native and hGPCR-signaling yeast, and use a model-guided approach to correlate gene expression to morphological changes. From this we demonstrate mating between haploid cells armed with hGPCRs and endogenous biosynthesis of their cognate ligands. Furthermore, we devise a ligand-free screening strategy for hGPCR compatibility with the yeast mating pathway and enable hGPCR-signaling in the probiotic yeast Saccharomyces boulardii. Combined, our findings enable new means to study mating, hGPCR-signaling, and cell-cell communication in a model eukaryote and yeast probiotics.One-sentence summaryEnabling sensing in probiotic yeast and synthetic yeast mating with human and fungal G protein-coupled receptors.
Panoramic visual statistics shape retina-wide organization of receptive fields
Authors: Gupta Divyansh , Młynarski Wiktor , Sumser Anton , Symonova Olga , Svatoň Jan , Joesch Maximilian 
Published: January 2022

AbstractStatistics of natural scenes are not uniform - their structure varies dramatically from ground to sky. It remains unknown whether these non-uniformities are reflected in the large-scale organization of the early visual system and what benefits such adaptations would confer. Here, by relying on the efficient coding hypothesis, we predict that changes in the structure of receptive fields across visual space increase the efficiency of sensory coding. We show experimentally that, in agreement with our predictions, receptive fields of retinal ganglion cells change their shape along the dorsoventral retinal axis, with a marked surround asymmetry at the visual horizon. Our work demonstrates that, according to principles of efficient coding, the panoramic structure of natural scenes is exploited by the retina across space and cell-types.
Error quantification in multi-parameter mapping facilitates robust estimation and enhanced group level sensitivity
Authors: Mohammadi Siawoosh , Streubel Tobias , Klock Leonie , Lutti Antoine , Pine Kerrin , Weber Sandra , Edwards Luke , Scheibe Patrick , Ziegler Gabriel , Gallinat Jürgen , Kühn Simone , Callaghan Martina F. , Weiskopf Nikolaus , Tabelow Karsten 
Published: January 2022

AbstractMulti-Parameter Mapping (MPM) is a comprehensive quantitative neuroimaging protocol that enables estimation of four physical parameters (longitudinal and effective transverse relaxation rates R1 and , proton density PD, and magnetization transfer saturation MTsat) that are sensitive to microstructural tissue properties such as iron and myelin content. Their capability to reveal microstructural brain differences, however, is tightly bound to controlling random noise and artefacts (e.g. caused by head motion) in the signal. Here, we introduced a method to estimate the local error of PD, R1 and MTsat maps that captures both noise and artefacts on a routine basis without requiring additional data. To investigate the method’s sensitivity to random noise, we calculated the model-based signal-to-noise ratio (mSNR) and showed in measurements and simulations that it correlated linearly with an experimental raw-image-based SNR map. We found that the mSNR varied with MPM protocols, magnetic field strength (3T vs. 7T) and MPM parameters: it halved from PD to R1 and decreased from PD to MTsat by a factor of 3-4. Exploring the artefact-sensitivity of the error maps, we generated robust MPM parameters using two successive acquisitions of each contrast and the acquisition-specific errors to down-weight erroneous regions. The resulting robust MPM parameters showed reduced variability at the group level as compared to their single-repeat or averaged counterparts. The error and mSNR maps may better inform power-calculations by accounting for local data quality variations across measurements. Code to compute the mSNR maps and robustly combined MPM maps is available in the open-source hMRI toolbox.
Sri Lankan Footprint in Global Aquatic Science Research: A Scientometric Analysis
Authors: Bandara Tharindu 
Published: January 2022

AbstractThe present study summarizes the research productivity and international collaboration in aquatic studies conducted by Sri Lankan scholars during 2000-2019. The study was based on the SCOPUS®database. R programming language, packagebibliometrixand Vosviewer software were employed in the analysis. Results of the present study indicate that increasing growth trend in the annual number of publications. A significant correlation (p<0.05) between the number of articles and per capita GDP (Gross Domestic Production) was also observed. Senior authors dominated in terms of the article count, citation count,hindex, and other author productivity indices. Journal of the National Science Foundation of Sri Lanka had the highest article count (n=33). Aquatic studies in Sri Lanka were more locally funded. Sri Lanka had strong research collaborations with Japan, South Korea and Australia. During 2000-2019, the transition of aquatic studies from lacustrine field studies to molecular lab-based studies were observed. The findings of the present study may provide a comprehensive understanding on the current context and future directions of aquatic studies in Sri Lanka.
Rational design yields molecular insights on leaf binding of the anchor peptide Macaque Histatin
Authors: Dittrich Jonas , Brethauer Christin , Goncharenko Liudmyla , Bührmann Jens , Zeisler-Diehl Viktoria , Pariyar Shyam , Jakob Felix , Kurkina Tetiana , Schreiber Lukas , Schwaneberg Ulrich , Gohlke Holger 
Published: January 2022

1AbstractIn times of a constantly growing world population and increasing demand for food, sustainable agriculture is crucial. To reduce the amount of applied nutrients, herbicides, and fungicides, the rainfastness of plant protection agents is of pivotal importance. As a result of protective agent wash-off, plant protection is lost, and soils and groundwater are severely polluted. To date, rainfastness of plant protection products is achieved by adding polymeric adjuvants to the agrochemicals. However, polymeric adjuvants will be regarded as microplastics in the future, and environmentally friendly alternatives are needed. Anchor peptides (APs) are promising biobased and biodegradable adhesion promoters. While the adhesion of anchor peptides to artificial surfaces, such as polymers, has already been investigated in theory and experimentally, exploiting the adhesion to biological surfaces remains challenging. The complex nature and composition of biological surfaces such as plant leaf and fruit surfaces complicate the generation of accurate models. Here, we present the first detailed three-layered atomistic model of the surface of apple leaves and use it to compute free energy profiles of the adhesion and desorption of APs to and from that surface. Our model is validated by a novel fluorescence-based MTP assay that mimicks these complex processes and allows quantifying them. For the AP Macaque Histatin, we demonstrate that aromatic and positively charged amino acids are essential for binding to the waxy apple leaf surface. The established protocols should generally be applicable for tailoring the binding properties of APs to biological interfaces.
Debiasing FracMinHash and deriving confidence intervals for mutation rates across a wide range of evolutionary distances
Authors: Hera Mahmudur Rahman , Pierce-Ward N. Tessa , Koslicki David 
Published: January 2022

AbstractSketching methods offer computational biologists scalable techniques to analyze data sets that continue to grow in size. MinHash is one such technique to estimate set similarity that has enjoyed recent broad application. However, traditional MinHash has previously been shown to perform poorly when applied to sets of very dissimilar sizes.FracMinHashwas recently introduced as a modification of MinHash to compensate for this lack of performance when set sizes differ. This approach has been successfully applied to metagenomic taxonomic profiling in the widely used toolsourmash gather. While experimental evidence has been encouraging, FracMinHash has not yet been analyzed from a theoretical perspective. In this paper, we perform such an analysis to derive various statistics of FracMinHash, and prove that while FracMinHash is not unbiased (in the sense that its expected value is not equal to the quantity it attempts to estimate), this bias is easily corrected for both the containment and Jaccard index versions. Next, we show how FracMinHash can be used to compute point estimates as well as confidence intervals for evolutionary mutation distance between a pair of sequences by assuming a simple mutation model. We also investigate edge cases where these analyses may fail, to effectively warn the users of FracMinHash indicating the likelihood of such cases. Our analyses show that FracMinHash estimates the containment of a genome in a large metagenome more accurately and more precisely when compared to traditional MinHash, and the point estimates and confidence intervals perform significantly better in estimating mutation distances.
PEGPH20, a PEGylated Human Hyaluronidase, Induces Radiosensitization by Reoxygenation In Pancreatic Cancer Xenografts. A Molecular Imaging Study
Authors: Seki Tomohiro , Saida Yu , Kishimoto Shun , Lee Jisook , Otowa Yasunori , Yamamoto Kazutoshi , Chandramouli Gadisetti VR , Devasahayam Nallathamby , Mitchell James B. , Brender Jeffery R. , Krishna Murali C. 
Published: January 2022

AbstractPEGylated human hyaluronidase (PEGPH20) enzymatically depletes hyaluronan, an important component of the extracellular matrix, in tumors. The resultant improvement in vascular patency and perfusion has been shown to increase the delivery of therapeutic molecules. We show that PEGPH20 also improves the efficacy of radiation therapy in a human pancreatic adenocarcinoma BxPC3 mouse model overexpressing hyaluronan synthase 3 (BxPC3-HAS3) while exerting little effect on the corresponding wild type tumors. Mice overexpressing HAS3 developed fast growing, radiation resistant tumors that became rapidly more hypoxic as time progressed. Treatment with PEGPH20 increased survival times when used in combination with radiation therapy, significantly more than either radiation therapy or PEGPH20 alone. Radiosensitization in BxPC3-HAS3 tumors was attributed to an increase in local pO2as studied by by EPR imaging. No effect on survival, radiation treatment, or pO2was seen in wild type tumors after PEGPH20 treatment. Dynamic contrast enhanced (DCE) MRI and MRI based blood volume imaging showed improved perfusion/permeability and local blood volume, respectively, in BxPC3-HAS3 tumors after PEGPH20 treatment, accounting for the increase in tumor oxygenation. Photoacoustic imaging indicated immediate changes in tumor oxygenation after treatment. Metabolic MRI using hyperpolarized [1-13C] pyruvate suggested a metabolic shift towards decreased glycolytic flux after PEGPH20 treatment. In summary, the results showed that PEGPH20 may be useful for radiosensitization of pancreatic cancer but only in the subset of tumors with substantial hyaluronan accumulation and the response of the treatment may potentially be monitored non-invasive imaging of the hemodynamic and metabolic changes in the tumor microenvironment.
Reciprocal epigenetic Sox2 regulation by SMAD1-SMAD3 is critical for anoikis resistance and metastasis in cancer
Authors: Shonibare Zainab , Monavarian Mehri , O’ Connell Kathleen , Altomare Diego , Shelton Abigail , Mehta Shubham , Jaskula-Sztul Renata , Phaeton Rebecca , Starr Mark D. , Whitaker Regina , Berchuck Andrew , Nixon Andrew B , Arend Rebecca , Lee Nam Y , Miller C. Ryan , Hempel Nadine , Mythreye Karthikeyan 
Published: January 2022

SummaryGrowth factors in the tumor environment are key regulators of cell survival and metastasis. Here we reveal, dichotomy between TGF-β superfamily growth factors BMP and TGF-β/activin, and their downstream SMAD effectors. Gene expression profiling uncovered Sox2 as a key signaling node regulated in an opposing manner by anoikis-promoting BMP2, 4 and 9, and anoikis-suppressing TGF-β and activin A. We find that Sox2 repression by BMPs robustly inhibits intraperitoneal tumor burden and increases survival in multiple ovarian cancer models. Repression of Sox2 is driven by SMAD1 dependent histone H3K27me3 recruitment and DNA methylation at SOX2’s promoter. Conversely, TGF-β and activin A promote Sox2 expression, and anoikis resistance by SMAD3 mediated histone H3K4me3 recruitment. We find that balancing Sox2 levels is critical for anoikis, as transcriptomics reveals regulation of key cell death pathways. Moreover, BMP-driven SMAD1 signaling can override TGF-β and activin’s effect on Sox2, which has clinical significance due to the high levels of TGF-β we find in ovarian cancer patients. Together, our findings identify Sox2 as a contextual and contrastingly regulated key node, downstream of TGF-β superfamily members controlling anoikis and metastasis in ovarian cancers.HighlightsSox2 is a key node for anoikis resistance in cancerSox2 is differentially regulated by TGF-β/activin and BMPs in broad cancersBMP9 is a robust metastasis suppressor by lowering Sox2Sox2 regulation is contextual, epigenetic and at the transcriptional level
Effect of cannabidiol on apoptosis and cellular interferon and interferon-stimulated gene responses to the SARS-CoV-2 genes ORF8, ORF10 and M protein
Authors: Fernandes Maria Fernanda , Chan John Zewen , Hung Chia Chun Joey , Tomczewski Michelle Victoria , Duncan Robin Elaine 
Published: January 2022

AbstractAimsTo study effects on cellular innate immune responses to novel genes ORF8 and ORF10, and the more conserved Membrane protein (M protein) from the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19, either alone, or in combination with cannabidiol (CBD).Main MethodsHEK293 cells were transfected with a control plasmid, or plasmids expressing ORF8, ORF10, or M protein, and assayed for cell number and markers of apoptosis at 24 h, and expression of interferon and interferon-stimulated genes at 14 h.Key findingsA significant reduction in cell number, and increase in early and late apoptosis, was found after 24 h in cells where expression of viral genes was combined with 1-2 μM CBD treatment, but not in control-transfected cells treated with CBD, or in cells expressing viral genes but treated only with vehicle. CBD (2 μM) augmented expression of IFNγ, IFNλ1 and IFNλ2/3, as well as the 2’-5’-oligoadenylate synthetase (OAS) family members OAS1, OAS2, OAS3, and OASL, in cells expressing ORF8, ORF10, and M protein. CBD also augmented expression of these genes in control cells not expressing viral genes, without enhancing apoptosis.SignificanceOur results demonstrate a poor ability of HEK293 cells to respond to SARS-CoV-2 genes alone, but suggest an augmented innate anti-viral response to these genes in the presence of CBD. Furthermore, our results indicate that CBD may prime components of the innate immune system, increasing readiness to respond to viral infection without activating apoptosis, and therefore could be studied for potential in prophylaxis.
Structural and functional impact by SARS-CoV-2 Omicron spike mutations
Authors: Zhang Jun , Cai Yongfei , Lavine Christy L. , Peng Hanqin , Zhu Haisun , Anand Krishna , Tong Pei , Gautam Avneesh , Mayer Megan L. , Rits-Volloch Sophia , Wang Shaowei , Sliz Piotr , Wesemann Duane R. , Yang Wei , Seaman Michael S. , Lu Jianming , Xiao Tianshu , Chen Bing 
Published: January 2022

AbstractThe Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), bearing an unusually high number of mutations, has become a dominant strain in many countries within several weeks. We report here structural, functional and antigenic properties of its full-length spike (S) protein with a native sequence in comparison with those of previously prevalent variants. Omicron S requires a substantially higher level of host receptor ACE2 for efficient membrane fusion than other variants, possibly explaining its unexpected cellular tropism. Mutations not only remodel the antigenic structure of the N-terminal domain of the S protein, but also alter the surface of the receptor-binding domain in a way not seen in other variants, consistent with its remarkable resistance to neutralizing antibodies. These results suggest that Omicron S has acquired an extraordinary ability to evade host immunity by excessive mutations, which also compromise its fusogenic capability.
A Longitudinal Study of Dominant E. coli Lineages and Antimicrobial Resistance in the Gut of Children Living in an Upper Middle-income Country
Authors: Calderón Diana , Cárdenas Paúl A. , Prado Belen , Graham Jay P. , Trueba Gabriel 
Published: January 2022

ABSTRACTThe gastrointestinal tract constitutes a complex and diverse ecosystem. Escherichia coli is one of the most frequently studied and characterized species in the gut ecosystem, nevertheless, there has been little research to determine their diversity and population dynamics in the intestines of children over time. In this prospective study, a fresh fecal sample was obtained from children longitudinally over one year (30 fecal samples at sampling period 1 and 22 fecal samples at sampling periods 2 and 3). From each stool sample, five E. coli colonies were randomly selected (n = 405 E. coli isolates total) in order to characterize the genotype and phenotypic antimicrobial resistance patterns. We found that all numerically dominant E. coli lineages in children’s intestines were transient colonizers, and antimicrobial resistance phenotypes of these strains varied significantly over time without any apparent selective force. Whole-genome sequencing of 3 isolates belonging to ST131 found in one child during the sampling period I and II indicated that isolates were three different ST 131 clones that carried extended-spectrum β-lactamase (ESBL) genes.IMPORTANCEThe length of residency and numeric dominance of antimicrobial-resistant E. coli may affect the extent to which an isolate contributes to the dissemination of antimicrobial resistance in a community. We studied the persistence of numerically dominant and antimicrobial-resistant lineages of E. coli in the human intestine. We found that E. coli lineages in the children's gut change considerably and rapidly over time. This study suggests that some phenotypic resistance patterns may result from the random distribution of genes in E. coli populations over time and may not be associated with differential exposure to antimicrobials.