bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of the adipose-derived mesenchymal stem cell delivery time for radiation-induced lung fibrosis treatment in rats
Authors: Zhang Yang , Jiang Xinping , Ren Liqun 
Published: April 2019

AbstractThe present study attempts to identify the optimal time duration for the administration of Ad-MSCs, in order to maximize its therapeutic benefits, and compare the degree of fibrosis among three different administration time points using the RILF rat model system. Ad-MSCs were delivered to Sprague-Dawley rats through the tail vein at the following different time points after thorax irradiation: two hours, seven days, and two hours + seven days. Post Ad-MSCs transplantation and the histopathological analysis of the lungs were performed along with analysis of inflammatory cytokine levels, including interleukin (IL)-1, IL-2, IL-6, IL-10 and tumor necrosis factor-α (TNF-α). In particular, pro-fibrotic factors (TGF-β1 and α-SMA) were also evaluated in serum and lung tissues. In addition, it was also determined whether Ad-MSCs had any role in inhibiting the transition of type II alveolar epithelial cells into fibroblasts in the lungs of injured rats. The present results demonstrated that the intravenous delivery of Ad-MSCs twice at the 2-hour and 7-day (R + MSC2h+7d group) was effective in reducing lung fibrosis for long term durations, when compared with single delivery either at the two-hour or 7-day time points. In addition, a marked anti-inflammatory effect was also observed in RILF rats in the R + MSC2h+7d group, as indicated by the reduced serum levels of pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) and increased levels of anti-inflammatory cytokines IL-10 and IL-2. Rats that were delivered twice with Ad-MSCs (R + MSC2h+7d group) exhibited significantly reduced TGF-β1 and α-SMA levels, in contrast to rats in the R + MSC7d or R + MSC2h groups, after four weeks. Furthermore, it was also noted that after four weeks, Ad-MSCs increased the number of lung epithelial cells (SP-C) and inhibited the lung fibroblastic cells (α-SMA) of rats in the R + MSC2h and R + MSC2h+7d groups. The present study concluded that two injections of Ad-MSCs (R + MSC2h+7d group) appear to be optimal for therapeutic efficacy and safety during RILF.
Reconciling cooperation, biodiversity and stability in complex ecological communities
Authors: Tu Chengyi , Suweis Samir , Grilli Jacopo , Formentin Marco , Maritan Amos 
Published: April 2019

AbstractEmpirical evidences show that ecosystems with high biodiversity can persist in time even in the presence of few types of resources and are more stable than low biodiverse communities. This evidence is contrasted by the conventional mathematical modeling, which predicts that the presence of many species and/or cooperative interactions are detrimental for ecological stability and persistence. Here we propose a modelling framework for population dynamics, which also include indirect cooperative interactions mediated by other species (e.g. habitat modification). We show that in the large system size limit, any number of species can coexist and stability increases as the number of species grows, if mediated cooperation is present, even in presence of exploitative or harmful interactions (e.g. antibiotics). Our theoretical approach thus shows that appropriate models of mediated cooperation naturally lead to a solution of the long-standing question about complexity-stability paradox and on how highly biodiverse communities can coexist.
Local Administration of GITR Agonistic Antibody Induces a Stronger Antitumor Immunity than Systemic Delivery
Authors: Narumi Kenta , Miyakawa Reina , Shibasaki Chihiro , Henmi Marina , Mizoguchi Yukihiro , Ueda Ryosuke , Hashimoto Hisayoshi , Hiraoka Nobuyoshi , Yoshida Teruhiko , Aoki Kazunori 
Published: April 2019

AbstractAn anti-glucocorticoid induced TNF receptor (GITR) agonistic antibody (Ab) induces an antitumor immunity with both stimulation of effector T cells and inhibition of regulatory T cell activity. To enhance GITR Ab-mediated tumor immunity, we focused on the intratumoral route, since a tumor-localized high concentration of Ab would confer activation of only tumor-infiltrating T cells. First, in a murine colon cancer model, we showed that the intratumoral delivery of Ab significantly increased the number of effector T cells infiltrated into tumors, and suppressed tumor growth more effectively than the intraperitoneal and intravenous injections did. Then, we found that the injection of Ab into the peritumoral area induced a systemic antitumor immunity at a similar level to the intratumoral injection. Therefore, we hypothesized that the transfer of locally administrated Ab into tumor-draining lymph nodes (TDLNs) plays an important role in inducing an effective immunity. In fact, intratumorally or peritumorally injected Ab was detected in TDLNs, and resection of Ab-injected TDLNs significantly reduced GITR Ab-mediated systemic tumor immunity. Intratumoral injection showed less number of auto-reactive T cells in the spleen than the intraperitoneal injection did. Intratumoral delivery of GITR Ab is a promising approach to induce an effective immunity compared to the systemic delivery.
A Pipeline for Faecal Host DNA Analysis by Absolute Quantification of LINE-1 and Mitochondrial Genomic Elements Using ddPCR
Authors: He Kuang , Fujiwara Hideaki , Zajac Cynthia , Sandford Erin , Reddy Pavan , Choi Sung Won , Tewari Muneesh 
Published: April 2019

AbstractStool contains DNA shed from cells of the gastrointestinal (GI) tract and has great potential as a bio-specimen for non-invasive, nucleic acid-based detection of GI diseases. Whereas methods for studying faecal microbiome DNA are plentiful, there is a lack of well-characterised procedures for stabilisation, isolation, and quantitative analysis of faecal host DNA. We report an optimised pipeline for faecal host DNA analysis from the point-of-collection to droplet digital PCR (ddPCR) absolute quantification of host-specific gene targets. We evaluated multiple methods for preservation and isolation of host DNA from stool to identify the highest performing methods. To quantify host DNA even if present in partially degraded form, we developed sensitive, human-specific short-amplicon ddPCR assays targeting repetitive nuclear genomic elements (LINE-1) and mitochondrial genes. We validated the ability of these optimised methods to perform absolute quantification of host DNA in 200 stool DNA extracts from samples that were serially collected from three healthy individuals and three hospitalised patients. These specimens allowed assessment of host DNA day-to-day variability in stool specimens with widely varying physical characteristics (i.e., Bristol scores). We further extended this approach to mouse stool analysis, to enable faecal host DNA studies in animal disease models as well.
Segmenting Mechanomyography Measures of Muscle Activity Phases Using Inertial Data
Authors: Woodward Richard B. , Stokes Maria J. , Shefelbine Sandra J. , Vaidyanathan Ravi 
Published: April 2019

AbstractElectromyography (EMG) is the standard technology for monitoring muscle activity in laboratory environments, either using surface electrodes or fine wire electrodes inserted into the muscle. Due to limitations such as cost, complexity, and technical factors, including skin impedance with surface EMG and the invasive nature of fine wire electrodes, EMG is impractical for use outside of a laboratory environment. Mechanomyography (MMG) is an alternative to EMG, which shows promise in pervasive applications. The present study used an exerting squat-based task to induce muscle fatigue. MMG and EMG amplitude and frequency were compared before, during, and after the squatting task. Combining MMG with inertial measurement unit (IMU) data enabled segmentation of muscle activity at specific points: entering, holding, and exiting the squat. Results show MMG measures of muscle activity were similar to EMG in timing, duration, and magnitude during the fatigue task. The size, cost, unobtrusive nature, and usability of the MMG/IMU technology used, paired with the similar results compared to EMG, suggest that such a system could be suitable in uncontrolled natural environments such as within the home.
Simulated microgravity promotes the formation of tridimensional cultures and stimulates pluripotency and a glycolytic metabolism in human hepatic and biliary tree stem/progenitor cells
Authors: Costantini Daniele , Overi Diletta , Casadei Luca , Cardinale Vincenzo , Nevi Lorenzo , Carpino Guido , Di Matteo Sabina , Safarikia Samira , Valerio Mariacristina , Melandro Fabio , Bizzarri Mariano , Manetti Cesare , Berloco Pasquale Bartolomeo , Gaudio Eugenio , Alvaro Domenico 
Published: April 2019

AbstractMany pivotal biological cell processes are affected by gravity. The aim of our study was to evaluate biological and functional effects, differentiation potential and exo-metabolome profile of simulated microgravity (SMG) on human hepatic cell line (HepG2) and human biliary tree stem/progenitor cells (hBTSCs). Both hBTSCs and HepG2 were cultured in a weightless and protected environment SGM produced by the Rotary Cell Culture System (Synthecon) and control condition in normal gravity (NG). Self-replication and differentiation toward mature cells were determined by culturing hBTSCs in Kubota’s Medium (KM) and in hormonally defined medium (HDM) tailored for hepatocyte differentiation. The effects on the expression and cell exo-metabolome profiles of SMG versus NG cultures were analyzed. SMG promotes tridimensional (3D) cultures of hBTSCs and HepG2. Significative increase of stemness gene expression (p < 0.05) has been observed in hBTSCs cultured in SMG when compared to NG condition. At the same time, the expression of hepatocyte lineage markers in hBTSCs differentiated by HDM was significantly lower (p < 0.05) in SMG compared to NG, demonstrating an impaired capability of hBTSCs to differentiate in vitro toward mature hepatocytes when cultured in SMG condition. Furthermore, in HepG2 cells the SMG caused a lower (p < 0.05 vs controls) transcription of CYP3A4, a marker of late-stage (i.e. Zone 3) hepatocytes. Exo-metabolome NMR-analysis showed that both cell cultures consumed a higher amount of glucose and lower glutamate in SMG respect to NG (p < 0.05). Moreover, hBTSCs media cultures resulted richer of released fermentation (lactate, acetate) and ketogenesis products (B-hydroxybutyrate) in SGM (p < 0.05) than NG. While, HepG2 cells showed higher consumption of amino acids and release of ketoacids (3-Methyl-2-oxovalerate, 2-oxo-4-methyl-valerate) and formiate with respect to normogravity condition (p < 0.05). Based on our results, SMG could be helpful for developing hBTSCs-derived liver devices. In conclusion, SMG favored the formation of hBTSCs and HepG2 3D cultures and the maintenance of stemness contrasting cell differentiation; these effects being associated with stimulation of glycolytic metabolism. Interestingly, the impact of SMG on stem cell biology should be taken into consideration for workers involved in space medicine programs.
Combination of acid β-glucosidase mutation and Saposin C deficiency in mice reveals Gba1 mutation dependent and tissue-specific disease phenotype
Authors: Liou Benjamin , Zhang Wujuan , Fannin Venette , Quinn Brian , Ran Huimin , Xu Kui , Setchell Kenneth D. R. , Witte David , Grabowski Gregory A. , Sun Ying 
Published: April 2019

AbstractGaucher disease is caused by mutations in GBA1 encoding acid β-glucosidase (GCase). Saposin C enhances GCase activity and protects GCase from intracellular proteolysis. Structure simulations indicated that the mutant GCases, N370S (0 S), V394L (4L) and D409V(9V)/H(9H), had altered function. To investigate the in vivo function of Gba1 mutants, mouse models were generated by backcrossing the above homozygous mutant GCase mice into Saposin C deficient (C*) mice. Without saposin C, the mutant GCase activities in the resultant mouse tissues were reduced by ~50% compared with those in the presence of Saposin C. In contrast to 9H and 4L mice that have normal histology and life span, the 9H;C* and 4L;C* mice had shorter life spans. 9H;C* mice developed significant visceral glucosylceramide (GC) and glucosylsphingosine (GS) accumulation (GC»GS) and storage macrophages, but lesser GC in the brain, compared to 4L;C* mice that presents with a severe neuronopathic phenotype and accumulated GC and GS primarily in the brain. Unlike 9V mice that developed normally for over a year, 9V;C* pups had a lethal skin defect as did 0S;C* mice resembled that of 0S mice. These variant Gaucher disease mouse models presented a mutation specific phenotype and underscored the in vivo role of Saposin C in the modulation of Gaucher disease.
The role of the environment in the evolution of nest shape in Australian passerines
Authors: Medina Iliana 
Published: April 2019

AbstractAvian nests present great variation in structure but, after excluding cavity nesters, probably the most obvious difference is that between open and domed nests. Some species lay their eggs in open structures, exposed to environmental variables, while other species build domed, enclosed nests with a roof, which are suggested to protect eggs and nestlings from weather conditions, high radiation levels, and predation. To date it is unclear which variables drove the evolution of different nest types. In this study, environmental and nest type information was extracted for continental Australian passerines, showing that species with open and closed nests are distributed in similar climates. However, species with open nests have larger ranges and are distributed in a wider variety of climatic conditions, suggesting open nests could be an evolutionary key innovation. This analysis was complemented with a detailed study of the evolution of particular nest traits in the largest Australasian avian radiation (Meliphagoidea), confirming that adult body size – but not environment – is an important factor in nest architecture, and larger species tend to build nests that are shallow and supported from underneath. Nest structure is a multidimensional trait that has probably evolved to match the phenotype of the nest owner, but that could also constrain or facilitate establishment in different environments.
Whole genome sequencing identifies bacterial factors affecting transmission of multidrug-resistant tuberculosis in a high-prevalence setting
Authors: Dixit Avika , Freschi Luca , Vargas Roger , Calderon Roger , Sacchettini James , Drobniewski Francis , Galea Jerome T. , Contreras Carmen , Yataco Rosa , Zhang Zibiao , Lecca Leonid , Kolokotronis Sergios-Orestis , Mathema Barun , Farhat Maha R. 
Published: April 2019

AbstractWhole genome sequencing (WGS) can elucidate Mycobacterium tuberculosis (Mtb) transmission patterns but more data is needed to guide its use in high-burden settings. In a household-based TB transmissibility study in Peru, we identified a large MIRU-VNTR Mtb cluster (148 isolates) with a range of resistance phenotypes, and studied host and bacterial factors contributing to its spread. WGS was performed on 61 of the 148 isolates. We compared transmission link inference using epidemiological or genomic data and estimated the dates of emergence of the cluster and antimicrobial drug resistance (DR) acquisition events by generating a time-calibrated phylogeny. Using a set of 12,032 public Mtb genomes, we determined bacterial factors characterizing this cluster and under positive selection in other Mtb lineages. Four of the 61 isolates were distantly related and the remaining 57 isolates diverged ca. 1968 (95%HPD: 1945–1985). Isoniazid resistance arose once and rifampin resistance emerged subsequently at least three times. Emergence of other DR types occurred as recently as within the last year of sampling. We identified five cluster-defining SNPs potentially contributing to transmissibility. In conclusion, clusters (as defined by MIRU-VNTR typing) may be circulating for decades in a high-burden setting. WGS allows for an enhanced understanding of transmission, drug resistance, and bacterial fitness factors.
Coral Skeleton δ15N as a Tracer of Historic Nutrient Loading to a Coral Reef in Maui, Hawaii
Authors: Murray Joseph , Prouty Nancy G. , Peek Sara , Paytan Adina 
Published: April 2019

AbstractExcess nutrient loading to nearshore environments has been linked to declining water quality and ecosystem health. Macro-algal blooms, eutrophication, and reduction in coral cover have been observed in West Maui, Hawaii, and linked to nutrient inputs from coastal submarine groundwater seeps. Here, we present a forty-year record of nitrogen isotopes (δ15N) of intra-crystalline coral skeletal organic matter in three coral cores collected at this site and evaluate the record in terms of changes in nitrogen sources. Our results show a dramatic increase in coral δ15N values after 1995, corresponding with the implementation of biological nutrient removal at the nearby Lahaina Wastewater Reclamation Facility (LWRF). High δ15N values are known to be strongly indicative of denitrification and sewage effluent, corroborating a previously suggested link between local wastewater injection and degradation of the reef environment. This record demonstrates the power of coral skeletal δ15N as a tool for evaluating nutrient dynamics within coral reef environments.
Cascading phase transformations in high carbon steel resulting in the formation of inverse bainite: An atomic scale investigation
Authors: Kannan Rangasayee , Wang Yiyu , Poplawsky Jonathan , Babu Sudarsanam Suresh , Li Leijun 
Published: April 2019

AbstractAtom probe tomography (APT) has been used to understand the redistribution of solutes during the isothermal cascading phase transformations from supersaturated austenite resulting in the formation of inverse bainite. Different cascading reactions resulting in the formation of inverse bainite, namely the cementite midrib formation, ferrite formation, secondary cementite formation, and the degenerated microstructure of inverse bainite have been studied in detail. Solute profiles across the different transformation interfaces indicate Negligible Partitioning Local Equilibrium (NPLE) type growth kinetics for cementite midrib, whereas a transition in growth kinetics from Para Equilibrium (PE) to Negligible Partitioning Local Equilibrium (NPLE) is observed for secondary cementite and ferrite transformation. The results provide a strong indication that the inverse bainitic transformation occurs as a consequence of individual cascading phase transformations starting from parent austenite, and the transformation of inverse bainite occurs in a similar manner to Widmanstatten ferrite/bainitic ferrite with carbon diffusion-controlled growth, and without any reconstructive or long-range diffusion of substitutional solutes.
The new nano-enabled phase map of ZrO2-Al2O3
Authors: Koltsov Iwona , Kimmel Giora , Stelmakh Svitlana , Sobczak Kamil , Lojkowski Witold 
Published: April 2019

AbstractRapid development of nanotechnology often requires verification of existing phase diagrams, which were suitable for bulk materials. This work presents a new phase map (phase diagram) for Al2O3-ZrO2 crystalline powders including the role of the nanoscale particles. Al2O3-ZrO2 composites are relevant for industry for applications demanding high hardness. The nanopowders were manufactured via co-precipitation process followed by microwave hydrothermal synthesis (MHS) at 270 °C, drying at room temperature and annealing in the temperature range 300–1500 °C. The phase composition was investigated using X-ray diffraction (XRD) and Rietveld refinement analysis. The grain size and size distribution were calculated using Rietveld refinement analysis and using transmission electron microscopy (TEM). A particular feature of the composites was the nanoisolation, separation of different phases on a nanoscale. This feature limited grain growth during annealing and permitted the phase diagram for a nano-enabled system to be determined, which turned out to be different from that of conventional composites. In particular, considerable solubility of Al3+ in ZrO2 was found for temperatures less than 1000 °C.
When the statistical MMN meets the physical MMN
Authors: Tsogli Vera , Jentschke Sebastian , Daikoku Tatsuya , Koelsch Stefan 
Published: April 2019

AbstractHow do listeners respond to prediction errors within patterned sequence of sounds? To answer this question we carried out a statistical learning study using electroencephalography (EEG). In a continuous auditory stream of sound triplets the deviations were either (a) statistical, in terms of transitional probability, (b) physical, due to a change in sound location (left or right speaker) or (c) a double deviants, i.e. a combination of the two. Statistical and physical deviants elicited a statistical mismatch negativity and a physical MMN respectively. Most importantly, we found that effects of statistical and physical deviants interacted (the statistical MMN was smaller when co-occurring with a physical deviant). Results show, for the first time, that processing of prediction errors due to statistical learning is affected by prediction errors due to physical deviance. Our findings thus show that the statistical MMN interacts with the physical MMN, implying that prediction error processing due to physical sound attributes suppresses processing of learned statistical properties of sounds.
3D Synthetic Peptide-based Architectures for the Engineering of the Enteric Nervous System
Authors: Brun Paola , Zamuner Annj , Peretti Alessandro , Conti Jessica , Messina Grazia M. L. , Marletta Giovanni , Dettin Monica 
Published: April 2019

AbstractDamage of enteric neurons and partial or total loss of selective neuronal populations are reported in intestinal disorders including inflammatory bowel diseases and necrotizing enterocolitis. To develop three-dimensional scaffolds for enteric neurons we propose the decoration of ionic-complementary self-assembling peptide (SAP) hydrogels, namely EAK or EAbuK, with bioactive motives. Our results showed the ability of EAK in supporting neuronal cell attachment and neurite development. Therefore, EAK was covalently conjugated to: RGD, (GRGDSP)4K (fibronectin), FRHRNRKGY (h-vitronectin, named HVP), IKVAV (laminin), and type 1 Insulin-like Growth Factor (IGF-1). Chemoselective ligation was applied for the SAP conjugation with IGF-1 and the other longer sequences. Freshly isolated murine enteric neurons attached and grew on all functionalized EAK but IGF-1. Cell-cell contact was evident on hydrogels enriched with (GRGDSP)4K and HVP. Moreover (GRGDSP)4K significantly increased mRNA expression of neurotrophin-3 and nerve growth factor, two trophic factors supporting neuronal survival and differentiation, whereas IKVAV decoration specifically increased mRNA expression of acetylcholinesterase and choline acetyltransferase, genes involved in synaptic communication between cholinergic neurons. Thus, decorated hydrogels are proposed as injectable scaffolds to supportin locosurvival of enteric neurons, foster synaptic communication, or drive the differentiation of neuronal subtypes.