bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Wnt signaling pathway suppresses radiation-induced dermal fibrosis
Authors: Lee Dong Won , Lee Won Jai , Cho Jaeho , Yun Chae-Ok , Roh Hyun , Chang Hsien Pin , Roh Tai Suk , Lee Ju Hee , Lew Dae Hyun 
Published: August 2020

AbstractProgressive fibrosis of the dermal tissues is a challenging complication of radiotherapy whose underlying mechanism is not fully understood, and there are few available treatments. The canonical Wnt/β-catenin signaling pathway plays an important role in fibrosis as well as in the epithelial-to-mesenchymal transition (EMT). We investigated whether inhibition of Wnt/β-catenin signaling with sLRP6E1E2, a molecule that binds to extracellular Wnt ligands, ameliorated radiation-induced fibrosis both in vitro and in vivo. Radiation with a single dose of 2 Gy not only facilitated fibrosis in cultured human dermal fibroblasts via activation of the Wnt/β-catenin pathway but also initiated EMT in cultured keratinocytes, developing collagen-producing mesenchymal cells. sLRP6E1E2-expressing adenovirus treatment exerted anti-fibrotic activity in irradiated cultured dermal fibroblasts and keratinocytes. In a mouse model, a single fraction of 15 Gy was delivered to the dorsal skins of 36 mice randomized into three groups: those receiving PBS, those receiving control adenovirus, and those receiving decoy Wnt receptor-expressing adenovirus (dE1-k35/sLRP6E1E2). The mice were observed for 16 weeks, and excessive deposition of type I collagen was suppressed by sLRP6E1E2-expressing adenovirus treatment. These results demonstrate that the modulation of the Wnt/β-catenin pathway has the potential to decrease the severity of radiation-induced dermal fibrosis.
Developmental changes in the accessible chromatin, transcriptome and Ascl1-binding correlate with the loss in Müller Glial regenerative potential
Authors: VandenBosch Leah S. , Wohl Stefanie G. , Wilken Matthew S. , Hooper Marcus , Finkbeiner Connor , Cox Kristen , Chipman Laura , Reh Thomas A. 
Published: August 2020

AbstractDiseases and damage to the retina lead to losses in retinal neurons and eventual visual impairment. Although the mammalian retina has no inherent regenerative capabilities, fish have robust regeneration from Müller glia (MG). Recently, we have shown that driving expression of Ascl1 in adult mouse MG stimulates neural regeneration. The regeneration observed in the mouse is limited in the variety of neurons that can be derived from MG; Ascl1-expressing MG primarily generate bipolar cells. To better understand the limits of MG-based regeneration in mouse retinas, we used ATAC- and RNA-seq to compare newborn progenitors, immature MG (P8-P12), and mature MG. Our analysis demonstrated developmental differences in gene expression and accessible chromatin between progenitors and MG, primarily in neurogenic genes. Overexpression of Ascl1 is more effective in reprogramming immature MG, than mature MG, consistent with a more progenitor-like epigenetic landscape in the former. We also used ASCL1 ChIPseq to compare the differences in ASCL1 binding in progenitors and reprogrammed MG. We find that bipolar-specific accessible regions are more frequently linked to bHLH motifs and ASCL1 binding. Overall, our analysis indicates a loss of neurogenic gene expression and motif accessibility during glial maturation that may prevent efficient reprogramming.
Insights on small molecule binding to the Hv1 proton channel from free energy calculations with molecular dynamics simulations
Authors: Lim Victoria T. , Geragotelis Andrew D. , Lim Nathan M. , Freites J. Alfredo , Tombola Francesco , Mobley David L. , Tobias Douglas J. 
Published: August 2020

AbstractHv1 is a voltage-gated proton channel whose main function is to facilitate extrusion of protons from the cell. The development of effective channel blockers for Hv1 can lead to new therapeutics for the treatment of maladies related to Hv1 dysfunction. Although the mechanism of proton permeation in Hv1 remains to be elucidated, a series of small molecules have been discovered to inhibit Hv1. Here, we computed relative binding free energies of a prototypical Hv1 blocker on a model of human Hv1 in an open state. We used alchemical free energy perturbation techniques based on atomistic molecular dynamics simulations. The results support our proposed open state model and shed light on the preferred tautomeric state of the channel blocker. This work lays the groundwork for future studies on adapting the blocker molecule for more effective inhibition of Hv1.
A micro-bioimpedance meter for monitoring insulin bioavailability in personalized diabetes therapy
Authors: Arpaia Pasquale , Cesaro Umberto , Frosolone Mirco , Moccaldi Nicola , Taglialatela Maurizio 
Published: August 2020

AbstractAn on-chip transducer, for monitoring noninvasively the insulin bio-availability in real time after administration in clinical diabetology, is proposed. The bioavailability is assessed as insulin decrease in situ after administration by means of local impedance measurement. Inter-and-intra individual reproducibility is enhanced by a personalized model, specific for the subject, identified and validated during each insulin administration. Such a real-time noninvasive bioavailability measurement allows to increase the accuracy of insulin bolus administration, by attenuating drawbacks of glycemic swings significantly. In the first part of this paper, the concept, the architecture, and the operation of the transducer, as well as details about its prototype, are illustrated. Then, the metrological characterization and validation are reported in laboratory, in vitro on eggplants, ex vivo on pig abdominal non-perfused muscle, and in vivo on a human subject, using injection as a reference subcutaneous delivery of insulin. Results of significant intra-individual reproducibility in vitro and ex vivo point out noteworthy scenarios for assessing insulin bioavailability in clinical diabetology.
Probing the influence of graphene oxide sheets size on the performance of label-free electrochemical biosensors
Authors: Eissa Shimaa , N’diaye Jeanne , Brisebois Patrick , Izquierdo Ricardo , Tavares Ana C. , Siaj Mohamed 
Published: August 2020

AbstractThe integration of graphene materials into electrochemical biosensing platforms has gained significant interest in recent years. Bulk quantities of graphene can be synthesized by oxidation of graphite to graphite oxide and subsequent exfoliation to graphene oxide (GO). However, the size of the resultant GO sheets changes from the parent graphite yielding a polydispersed solution of sizes ranging from a few nanometers to tens of micrometers. Here, we investigate the direct effect of GO sheets sizes on biosensor performance. We separated different GO sheets sizes, and we characterized them via atomic force, scanning electron, Raman and X-ray photoelectron spectroscopies and solid state nuclear magnetic resonance (NMR). As proof of concept, the sensing performance of these GO samples was probed using a well-known ssDNA aptasensor against microcystin-LR toxin and an immunosensor against β-lactoglobulin. The resulting aptasensors and immunosensors are fabricated by using covalent attachment and physical adsorption. We found that the aptasensors fabricated using physical adsorption, the binding signal variation was dramatically increased with increasing the GO sheet size. In contrast, for the aptasensor fabricated using covalent immobilization, the binding signal variation decreased with increasing GO sheet size. However, for the β-lactoglobulin immunosensors, the optimum signals were observed at intermediate GO sheet size. GO sheet size could enhance or inhibit the sensitivity of the graphene-based electrochemical sensors. Our results demonstrate that controlling the size of GO sheets may have a profound impact in specific biosensing applications.
The influence of hydrodynamic exposure on carbon storage and nutrient retention in eelgrass (Zostera marina L.) meadows on the Swedish Skagerrak coast
Authors: Dahl Martin , Asplund Maria E. , Björk Mats , Deyanova Diana , Infantes Eduardo , Isaeus Martin , Nyström Sandman Antonia , Gullström Martin 
Published: August 2020

AbstractCold-temperate seagrass (Zostera marina) meadows provide several important ecosystem services, including trapping and storage of sedimentary organic carbon and nutrients. However, seagrass meadows are rapidly decreasing worldwide and there is a pressing need for protective management of the meadows and the organic matter sinks they create. Their carbon and nutrient storage potential must be properly evaluated, both at present situation and under future climate change impacts. In this study, we assessed the effect of wave exposure on sedimentary carbon and nitrogen accumulation using existing data from 53 Z. marina meadows at the Swedish west coast. We found that meadows with higher hydrodynamic exposure had larger absolute organic carbon and nitrogen stocks (at 0–25 cm depth). This can be explained by a hydrodynamically induced sediment compaction in more exposed sites, resulting in increased sediment density and higher accumulation (per unit volume) of sedimentary organic carbon and nitrogen. With higher sediment density, the erosion threshold is assumed to increase, and as climate change-induced storms are predicted to be more common, we suggest that wave exposed meadows can be more resilient toward storms and might therefore be even more important as carbon- and nutrient sinks in the future.
Experimental realization of controlled quantum teleportation of arbitrary qubit states via cluster states
Authors: Kumar Abhijeet , Haddadi Saeed , Pourkarimi Mohammad Reza , Behera Bikash K. , Panigrahi Prasanta K. 
Published: August 2020

AbstractControlled quantum teleportation involves a third party as a controller for the teleportation of state. Here, we present the novel protocols for controlling teleportation of the arbitrary two-qubit and three-qubit states through five-qubit and seven-qubit cluster states respectively. In these schemes, Alice sends the arbitrary qubit states to the remote receiver Bob through the cluster states as quantum channels under the control of Charlie. Bob can recover the mentioned states by making appropriate unitary operations, and we point out that the efficiency in our schemes is 100%. In the process of our analysis, we find the classical communication cost in our protocols is remarkably reduced when compared to the previous protocols. We perform the experimental realization of the above protocols on “IBM 16 Melbourne” quantum computer and “IBM quantum simulator” and we calculate the fidelity. We also examine the security analysis against Charlie, and these schemes which we considered here are secure against Charlie’s attacks.
In-situ monitoring of an organic sample with electric field determination during cold plasma jet exposure
Authors: Slikboer Elmar , Sobota Ana , Garcia-Caurel Enric , Guaitella Olivier 
Published: August 2020

AbstractPockels-based Mueller polarimetry is presented as a novel diagnostic technique for studying time and space-resolved and in-situ the interaction between an organic sample (a layer of onion cells) and non-thermal atmospheric pressure plasma. The effect of plasma is complex, as it delivers electric field, radicals, (UV) radiation, non-uniform in time nor in space. This work shows for the first time that the plasma-surface interaction can be characterized through the induced electric field in an electro-optic crystal (birefringence caused by the Pockels effect) while at the same moment the surface evolution of the targeted sample is monitored (depolarization) which is attached to the crystal. As Mueller polarimetry allows for separate detection of depolarization and birefringence, it is possible to decouple the entangled effects of the plasma. In the sample three spatial regions are identified where the surface evolution of the sample differs. This directly relates to the spatial in-homogeneity of the plasma at the surface characterized through the detected electric field. The method can be applied in the future to investigate plasma-surface interactions for various targets ranging from bio-films, to catalytic surfaces and plastics/polymers.
The conversion of forestland into agricultural land without appropriate measures to conserve SOM leads to the degradation of physical and rheological soil properties
Authors: Tolimir Miodrag , Kresović Branka , Životić Ljubomir , Dragović Snežana , Dragović Ranko , Sredojević Zorica , Gajić Boško 
Published: August 2020

AbstractThis study was conducted to compare soil particle density (ρs), soil total porosity (TP), liquid limit (LL), plastic limit (PL), and plasticity index, and their relations with soil organic matter (SOM), of non-carbonate silty clay Fluvisols under different land uses. Three neighboring land uses were studied: native deciduous forest, arable land, and meadow, managed in the same way for more than 100 years. Soil was collected from 27 soil profiles and from three depths (0–15, 15–30 and 30–45 cm). Land use caused statistically significant but different impacts on soil properties, particularly in the topsoil. The forest topsoil measured the lowest ρs and bulk density (ρb) but the highest SOM and soil water content at PL, compared to meadow and arable soil. Statistically significant linear relationship was observed with the SOM content and ρs (− 0.851**), ρb (− 0.567**), calculated TP (0.567**) and measured TP (− 0.280**). There was a nonlinear relationship between SOM and LL (0.704**) and PL (0.845**) at the topsoil. The findings suggested that SOM content strongly affected ρs, ρb, TP, LL and LP. This regional study showed that the conversion of forestland into agricultural land without appropriate measures to conserve SOM leads to the degradation of physical and rheological soil properties.
Principles of computer-controlled linear motion applied to an open-source affordable liquid handler for automated micropipetting
Authors: Florian David C. , Odziomek Mateusz , Ock Cerie L. , Chen Hannah , Guelcher Scott A. 
Published: August 2020

AbstractOTTO is an open-source automated liquid handler that can be fabricated at a cost of $1,500 using off-the-shelf and 3D-printable parts as an alternative to commercial devices. Open-source approaches have been applied to build syringe pumps, centrifuges, and other laboratory equipment. These devices are affordable but generally rely on a single motor to perform simple operations and thus do not fully utilize the potential of the Maker Movement. Open-source linear actuators and microcontrollers enable the fabrication of more complex laboratory instruments that rely on 3D positioning and accurate dispensing of fluids, such as automated liquid handlers. These instruments can be built rapidly and affordably, thereby providing access to highly reproducible sample preparation for common biological assays such as qPCR. We applied the design principles of speed and accuracy, unattended automation, and open-source components to build an automated liquid handler that controls micropipetting of liquids in 3D space at speeds and positional resolutions required for qPCR. In benchmarking studies, OTTO showed accuracy and sample preparation times comparable to manual qPCR. The ability to control linear motion and liquid dispensing using affordable off-the-shelf and 3D-printable parts can facilitate the adoption of open-source automated liquid handlers for qPCR, bioplotting, and other bioinstrumentation applications.
Salmonella enterica serovar Typhi exposure elicits ex vivo cell-type-specific epigenetic changes in human gut cells
Authors: Sztein Marcelo B. , Bafford Andrea C. , Salerno-Goncalves Rosângela 
Published: August 2020

AbstractSalmonella enterica serovar Typhi (S. Typhi) causes substantial morbidity and mortality worldwide, particularly among young children. Humans develop an array of mucosal immune responses following S. Typhi infection. Whereas the cellular mechanisms involved in S. Typhi infection have been intensively studied, very little is known about the early chromatin modifications occurring in the human gut microenvironment that influence downstream immune responses. To address this gap in knowledge, cells isolated from human terminal ileum exposed ex vivo to the wild-type S. Typhi strain were stained with a 33-metal-labeled antibody panel for mass cytometry analyses of the early chromatin modifications modulated by S. Typhi. We measured the cellular levels of 6 classes of histone modifications, and 1 histone variant in 11 major cell subsets (i.e., B, CD3 + T, CD4 + T, CD8 + T, NK, TCR-γδ, Mucosal associated invariant (MAIT), and NKT cells as well as monocytes, macrophages, and epithelial cells). We found that arginine methylation might regulate the early-differentiation of effector-memory CD4+ T-cells following exposure to S. Typhi. We also found S. Typhi-induced post-translational modifications in histone methylation and acetylation associated with epithelial cells, NKT, MAIT, TCR-γδ, Monocytes, and CD8 + T-cells that are related to both gene activation and silencing.
Integrative analyses of transcriptomics and metabolomics upon seed germination of foxtail millet in response to salinity
Authors: Pan Jiaowen , Li Zhen , Dai Shaojun , Ding Hanfeng , Wang Qingguo , Li Xiaobo , Ding Guohua , Wang Pengfei , Guan Yanan , Liu Wei 
Published: August 2020

AbstractSalinity stress has become an expanding threat to food security worldwide. Revealing the mechanisms of salinity tolerance in plants has immense significance. Foxtail millet (Setaria italica L.) has been regarded as a model crop for exploring mechanisms under stress, considering its extreme adaptation abilities to adverse ecologies. In present study, two foxtail millet cultivars of Yugu2 and An04 with contrasting salt tolerance properties were investigated through integrative analyses of transcriptomics and metabolomics. In the transcriptomics results, 8887 and 12,249 DEGs were identified in Yugu2 and An04 in response to salinity, respectively, and 3149 of which were overlapped between two varieties. These salinity-responsive genes indicated that ion transport, redox homeostasis, phytohormone metabolism, signaling and secondary metabolism were enriched in Yugu2 by GO and KEGG analyses. The integrative omics analysis implied that phenylpropanoid, flavonoid and lignin biosynthesis pathways, and lysophospholipids were vital in determining the foxtail millet salinity tolerance. Importantly, the tolerance of Yugu2 attributed to higher efficiencies of ion channel and antioxidant system. All these provide a comprehensive regulatory network of foxtail millet to cope with salinity, and shed some lights on salt tolerance which is relevant for other cereal crops.
The P-glycoprotein repertoire of the equine parasitic nematode Parascaris univalens
Authors: Gerhard Alexander P. , Krücken Jürgen , Heitlinger Emanuel , Janssen I. Jana I. , Basiaga Marta , Kornaś Sławomir , Beier Céline , Nielsen Martin K. , Davis Richard E. , Wang Jianbin , von Samson-Himmelstjerna Georg 
Published: August 2020

AbstractP-glycoproteins (Pgp) have been proposed as contributors to the widespread macrocyclic lactone (ML) resistance in several nematode species including a major pathogen of foals, Parascaris univalens. Using new and available RNA-seq data, ten different genomic loci encoding Pgps were identified and characterized by transcriptome-guided RT-PCRs and Sanger sequencing. Phylogenetic analysis revealed an ascarid-specific Pgp lineage, Pgp-18, as well as two paralogues of Pgp-11 and Pgp-16. Comparative gene expression analyses in P. univalens and Caenorhabditis elegans show that the intestine is the major site of expression but individual gene expression patterns were not conserved between the two nematodes. In P. univalens, PunPgp-9, PunPgp-11.1 and PunPgp-16.2 consistently exhibited the highest expression level in two independent transcriptome data sets. Using RNA-Seq, no significant upregulation of any Pgp was detected following in vitro incubation of adult P. univalens with ivermectin suggesting that drug-induced upregulation is not the mechanism of Pgp-mediated ML resistance. Expression and functional analyses of PunPgp-2 and PunPgp-9 in Saccharomyces cerevisiae provide evidence for an interaction with ketoconazole and ivermectin, but not thiabendazole. Overall, this study established reliable reference gene models with significantly improved annotation for the P. univalens Pgp repertoire and provides a foundation for a better understanding of Pgp-mediated anthelmintic resistance.
ApcMin/+ tumours and normal mouse small intestines show linear metabolite concentration and DNA cytosine hydroxymethylation gradients from pylorus to colon
Authors: Madhu Basetti , Uribe-Lewis Santiago , Bachman Martin , Murrell Adele , Griffiths John R. 
Published: August 2020

AbstractTopographical variations of metabolite concentrations have been reported in the duodenum, jejunum and ileum of the small intestine, and in human intestinal tumours from those regions, but there are no published metabolite concentrations measurements correlated with linear position in the mouse small intestine or intestinal tumours. Since DNA methylation dynamics are influenced by metabolite concentrations, they too could show linear anatomical variation. We measured metabolites by HR-MAS 1H NMR spectroscopy and DNA cytosine modifications by LC/MS, in normal small intestines of C57BL/6J wild-type mice, and in normal and tumour samples from ApcMin/+ mice. Wild-type mouse intestines showed approximately linear, negative concentration gradations from the pylorus (i.e. the junction with the stomach) of alanine, choline compounds, creatine, leucine and valine. ApcMin/+ mouse tumours showed negative choline and valine gradients, but a positive glycine gradient. 5-Hydroxymethylcytosine showed a positive gradient in the tumours. The linear gradients we found along the length of the mouse small intestine and in tumours contrast with previous reports of discrete concentration changes in the duodenum, jejunum and ileum. To our knowledge, this is also the first report of a systematic measurement of global levels of DNA cytosine modification in wild-type and ApcMin/+ mouse small intestine.
Molecular characterization of pyridoxine 5′-phosphate oxidase and its pathogenic forms associated with neonatal epileptic encephalopathy
Authors: Barile Anna , Nogués Isabel , di Salvo Martino L. , Bunik Victoria , Contestabile Roberto , Tramonti Angela 
Published: August 2020

AbstractDefects of vitamin B6 metabolism are responsible for severe neurological disorders, such as pyridoxamine 5′-phosphate oxidase deficiency (PNPOD; OMIM: 610090), an autosomal recessive inborn error of metabolism that usually manifests with neonatal-onset severe seizures and subsequent encephalopathy. At present, 27 pathogenic mutations of the gene encoding human PNPO are known, 13 of which are homozygous missense mutations; however, only 3 of them have been characterised with respect to the molecular and functional properties of the variant enzyme forms. Moreover, studies on wild type and variant human PNPOs have so far largely ignored the regulation properties of this enzyme. Here, we present a detailed characterisation of the inhibition mechanism of PNPO by pyridoxal 5′-phosphate (PLP), the reaction product of the enzyme. Our study reveals that human PNPO has an allosteric PLP binding site that plays a crucial role in the enzyme regulation and therefore in the regulation of vitamin B6 metabolism in humans. Furthermore, we have produced, recombinantly expressed and characterised several PNPO pathogenic variants responsible for PNPOD (G118R, R141C, R225H, R116Q/R225H, and X262Q). Such replacements mainly affect the catalytic activity of PNPO and binding of the enzyme substrate and FMN cofactor, leaving the allosteric properties unaltered.