bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination of irreversible electroporation with sustained release of a synthetic membranolytic polymer for enhanced cancer cell killing
Authors: Hanson Samuel M. , Forsyth Bruce , Wang Chun 
Published: May 2021

AbstractIrreversible electroporation (IRE) is used clinically as a focal therapy to ablate solid tumors. A critical disadvantage of IRE as a monotherapy for cancer is the inability of ablating large tumors, because the electric field strength required is often too high to be safe. Previous reports indicate that cells exposed to certain cationic small molecules and surfactants are more vulnerable to IRE at lower electric field strengths. However, low-molecular-weight IRE sensitizers may suffer from suboptimal bioavailability due to poor stability and a lack of control over spatiotemporal accumulation in the tumor tissue. Here, we show that a synthetic membranolytic polymer, poly(6-aminohexyl methacrylate) (PAHM), synergizes with IRE to achieve enhanced cancer cell killing. The enhanced efficacy of the combination therapy is attributed to PAHM-mediated sensitization of cancer cells to IRE and to the direct cell killing by PAHM through membrane lysis. We further demonstrate sustained release of PAHM from embolic beads over 1 week in physiological medium. Taken together, combining IRE and a synthetic macromolecular sensitizer with intrinsic membranolytic activity and sustained bioavailability may present new therapeutic opportunities for a wide range of solid tumors.
Estimating the impact of control measures to prevent outbreaks of COVID-19 associated with air travel into a COVID-19-free country
Authors: Wilson Nick , Baker Michael G. , Blakely Tony , Eichner Martin 
Published: May 2021

AbstractWe aimed to estimate the risk of COVID-19 outbreaks associated with air travel to a COVID-19-free country [New Zealand (NZ)]. A stochastic version of the SEIR model CovidSIM v1.1, designed specifically for COVID-19 was utilised. We first considered historical data for Australia before it eliminated COVID-19 (equivalent to an outbreak generating 74 new cases/day) and one flight per day to NZ with no interventions in place. This gave a median time to an outbreak of 0.2 years (95% range of simulation results: 3 days to 1.1 years) or a mean of 110 flights per outbreak. However, the combined use of a pre-flight PCR test of saliva, three subsequent PCR tests (on days 1, 3 and 12 in NZ), and various other interventions (mask use and contact tracing) reduced this risk to one outbreak after a median of 1.5 years (20 days to 8.1 years). A pre-flight test plus 14 days quarantine was an even more effective strategy (4.9 years; 2,594 flights). For a much lower prevalence (representing only two new community cases per week in the whole of Australia), the annual risk of an outbreak with no interventions was 1.2% and had a median time to an outbreak of 56 years. In contrast the risks associated with travellers from Japan and the United States was very much higher and would need quarantine or other restrictions. Collectively, these results suggest that multi-layered interventions can markedly reduce the risk of importing the pandemic virus via air travel into a COVID-19-free nation. For some low-risk source countries, there is the potential to replace 14-day quarantine with alternative interventions. However, all approaches require public and policy deliberation about acceptable risks, and continuous careful management and evaluation.
Impacts of sheep versus cattle livestock systems on birds of Mediterranean grasslands
Authors: Ramos Rita F. , Diogo João A. , Santana Joana , Silva João P. , Reino Luís , Schindler Stefan , Beja Pedro , Lomba Angela , Moreira Francisco 
Published: May 2021

AbstractMediterranean pastures are experiencing strong changes in management, involving shifts from sheep to cattle-based livestock systems. The impacts of such shifts on biodiversity are still poorly understood. Here, we sought to contrast the grazing regime, vegetation structure, bird species richness and abundance, between sheep and cattle grazed parcels, to understand the mechanisms through which management decisions impact farmland birds. During spring 2019, we characterized livestock management, bird populations and sward structure in 23 cattle and 27 sheep grazed parcels. We used a Structural Equation Model to infer the direct and indirect effects of sheep and cattle grazing on birds. Although no effects were found on overall species richness, there were species-specific responses to sheep and cattle grazed systems. Grazing pressure (variable integrating stocking rate and the number of days in the parcel) had negative impacts on the prevalence/abundance of Zitting Cisticola, Corn Bunting and Little Bustard, either directly or indirectly, through the effects of grazing pressure on vegetation height. Animal density and vegetation cover had direct positive effects in Galerida spp. and Common Quail, respectively. Zitting Cisticola and Little Bustard also showed a direct response to livestock type. Our study emphasizes the importance of grazing pressure as a driver of negative impacts for bird populations in Mediterranean grasslands. Since the ongoing transition from sheep to cattle-based systems involves increases in stocking rate, and therefore potentially higher grazing pressure, we propose a policy change to cap the maximum allowed grazing pressure. At the landscape scale, a mix of sheep and cattle grazed fields would be beneficial for maintaining bird diversity.
Development of a novel method for the in-situ dechlorination of immovable iron elements: optimization of Cl− extraction yield through experimental design
Authors: Veneranda Marco , Prieto-Taboada Nagore , Carrero Jose Antonio , Costantini Ilaria , Larrañaga Aitor , Castro Kepa , Arana Gorka , Madariaga Juan Manuel 
Published: May 2021

AbstractThe conservation of iron objects exposed to marine aerosol is threatened by the formation of akaganeite, a highly unstable Cl-bearing corrosion phase. As akaganeite formation is responsible of the exfoliation of the rust layer, chlorides trigger a cyclic alteration phenomenon that often ends with the total consumption of the iron core. To prevent this degradation process, movable iron elements (e.g. archaeometallurgical artefacts) are generally immersed in alkaline dechlorination baths. Aiming to transfer this successful method to the treatment of immovable iron objects, we propose the in-situ application of alkaline solutions through the use of highly absorbent wraps. As first step of this novel research line, the present work defines the best desalination solution to be used and optimizes its extraction yield. After literature review, a screening experimental design was performed to understand the single and synergic effects of common additives used for NaOH baths. Once the most effective variables were selected, an optimization design was carried out to determine the optimal conditions to be set during treatment. According to the experimental work here presented, the use of 0.7 M NaOH solutions applied at high temperatures (above 50 °C) is recommended. Indeed, these conditions enhance chloride extraction and iron leaching inhibition, while promoting corrosion stabilization.
hTERT-immortalized gingival fibroblasts respond to cytokines but fail to mimic primary cell responses to Porphyromonas gingivalis
Authors: Lagosz-Cwik Katarzyna B. , Wielento Aleksandra , Lipska Weronika , Kantorowicz Malgorzata , Darczuk Dagmara , Kaczmarzyk Tomasz , Gibbs Susan , Potempa Jan , Grabiec Aleksander M. 
Published: May 2021

AbstractIn periodontitis, gingival fibroblasts (GFs) interact with and respond to oral pathogens, significantly contributing to perpetuation of chronic inflammation and tissue destruction. The aim of this study was to determine the usefulness of the recently released hTERT-immortalized GF (TIGF) cell line for studies of host–pathogen interactions. We show that TIGFs are unable to upregulate expression and production of interleukin (IL)-6, IL-8 and prostaglandin E2 upon infection with Porphyromonas gingivalis despite being susceptible to adhesion and invasion by this oral pathogen. In contrast, induction of inflammatory mediators in TNFα- or IL-1β-stimulated TIGFs is comparable to that observed in primary GFs. The inability of TIGFs to respond directly to P. gingivalis is caused by a specific defect in Toll-like receptor-2 (TLR2) expression, which is likely driven by TLR2 promoter hypermethylation. Consistently, TIGFs fail to upregulate inflammatory genes in response to the TLR2 agonists Pam2CSK4 and Pam3CSK4. These results identify important limitations of using TIGFs to study GF interaction with oral pathogens, though these cells may be useful for studies of TLR2-independent processes. Our observations also emphasize the importance of direct comparisons between immortalized and primary cells prior to using cell lines as models in studies of any biological processes.
Adsorption of bio-organic eco-corona molecules reduces the toxic response to metallic nanoparticles in Daphnia magna
Authors: Ekvall Mikael T. , Hedberg Jonas , Odnevall Wallinder Inger , Malmendal Anders , Hansson Lars-Anders , Cedervall Tommy 
Published: May 2021

AbstractAs the use of engineered nanomaterials increases, so does the risk of them spreading to natural ecosystems. Hitherto, knowledge regarding the toxic properties of nanoparticles (NP’s) and their potential interactions with natural bio-organic molecules adsorbed to them, and thereby forming surface coronas, is limited. However, we show here that the toxic effect of NPs of tungsten carbide cobalt (WC–Co) and cobalt (Co) on the crustacean Daphnia magna is postponed in the presence of natural biological degradation products (eco-corona biomolecules). For Daphnia exposed to WC–Co NPs the survival time increased with 20–25% and for Co NPs with 30–47% after mixing the particles with a solution of eco-corona biomolecules before exposure. This suggests that an eco-corona, composed of biomolecules always present in natural ecosystems, reduces the toxic potency of both studied NPs. Further, the eco-coronas did not affect the particle uptake, suggesting that the reduction in toxicity was related to the particle-organism interaction after eco-corona formation. In a broader context, this implies that although the increasing use and production of NPs may constitute a novel, global environmental threat, the acute toxicity and long-term effects of some NPs will, at least under certain conditions, be reduced as they enter natural ecosystems.
Prematurity alters the progenitor cell program of the upper respiratory tract of neonates
Authors: Shui Jessica E. , Wang Wei , Liu Helu , Stepanova Anna , Liao Grace , Qian Jun , Ai Xingbin , Ten Vadim , Lu Jining , Cardoso Wellington V. 
Published: May 2021

AbstractThe impact of prematurity on human development and neonatal diseases, such as bronchopulmonary dysplasia, has been widely reported. However, little is known about the effects of prematurity on the programs of stem cell self-renewal and differentiation of the upper respiratory epithelium, which is key for adaptation to neonatal life. We developed a minimally invasive methodology for isolation of neonatal basal cells from nasopharyngeal (NP) aspirates and performed functional analysis in organotypic cultures to address this issue. We show that preterm NP progenitors have a markedly distinct molecular signature of abnormal proliferation and mitochondria quality control compared to term progenitors. Preterm progenitors had lower oxygen consumption at baseline and were unable to ramp up consumption to the levels of term cells when challenged. Although they formed a mucociliary epithelium, ciliary function tended to decline in premature cells as they differentiated, compared to term cells. Together, these differences suggested increased sensitivity of preterm progenitors to environmental stressors under non-homeostatic conditions.
Addressing the COVID-19 transmission in inner Brazil by a mathematical model
Authors: Almeida G. B. , Vilches T. N. , Ferreira C. P. , Fortaleza C. M. C. B. 
Published: May 2021

AbstractIn 2020, the world experienced its very first pandemic of the globalized era. A novel coronavirus, SARS-CoV-2, is the causative agent of severe pneumonia and has rapidly spread through many nations, crashing health systems and leading a large number of people to death. In Brazil, the emergence of local epidemics in major metropolitan areas has always been a concern. In a vast and heterogeneous country, with regional disparities and climate diversity, several factors can modulate the dynamics of COVID-19. What should be the scenario for inner Brazil, and what can we do to control infection transmission in each of these locations? Here, a mathematical model is proposed to simulate disease transmission among individuals in several scenarios, differing by abiotic factors, social-economic factors, and effectiveness of mitigation strategies. The disease control relies on keeping all individuals’ social distancing and detecting, followed by isolating, infected ones. The model reinforces social distancing as the most efficient method to control disease transmission. Moreover, it also shows that improving the detection and isolation of infected individuals can loosen this mitigation strategy. Finally, the effectiveness of control may be different across the country, and understanding it can help set up public health strategies.
Direct gas-in-place measurements prove much higher production potential than expected for shale formations
Authors: Mahzari Pedram , Mitchell Thomas M. , Jones Adrian P. , Westacott Donald , Striolo Alberto 
Published: May 2021

AbstractShale gas exploitation has been the game-changer in energy development of the past decade. However, the existing methods of estimating gas in place in deep formations suffer from large uncertainties. Here, we demonstrate, by using novel high-pressure experimental techniques, that the gas in place within deep shale gas reservoirs can be up to five times higher than that estimated by implementing industry standard approaches. We show that the error between our laboratory approach and the standard desorption test is higher for gases with heavier compositions, which are of strongest commercial interests. The proposed instrumentation is reliable for deep formations and, provides quick assessment of the potential for the gas in place, which could be useful for assessing hydrocarbon reservoirs, and the potential for geological carbon sequestration of a given formation.
The early drift of the Indian plate
Authors: Jokat Wilfried , Altenbernd Tabea , Eagles Graeme , Geissler Wolfram H. 
Published: May 2021

AbstractPlate kinematic models propose that India and Sri Lanka (INDSRI) separated from Antarctica by extremely slow seafloor spreading that started in early Cretaceous times, and that a long-distance ridge jump left a continental fragment stranded off the Antarctic margin under the Southern Kerguelen Plateau 1-3. Here, we present newly acquired magnetic and deep wide-angle seismic data that require a fundamental re-evaluation of these concepts. The new data clearly define the onset of oceanic crust in the Enderby Basin and off southern Sri Lanka, and date its formation with unprecedented confidence. The revised timing indicates that India and Sri Lanka detached from Antarctica earlier in the east than in the west. Furthermore, no compelling evidence for an extinct spreading axis is found in the Enderby Basin. A refined plate motion model indicates that India and Sri Lanka departed from Antarctica without major rift jumps, but by the action of three spreading ridges with different timings and velocities that must have been accommodated by significant intracontinental deformation.
Folliculin haploinsufficiency causes cellular dysfunction of pleural mesothelial cells
Authors: Okamoto Shouichi , Ebana Hiroki , Kurihara Masatoshi , Mitani Keiko , Kobayashi Etsuko , Hayashi Takuo , Sekimoto Yasuhito , Nishino Koichi , Otsuji Mizuto , Kumasaka Toshio , Takahashi Kazuhisa , Seyama Kuniaki 
Published: May 2021

AbstractBirt–Hogg–Dubé syndrome (BHDS), an autosomal dominant inheritance disease caused by folliculin (FLCN) mutations, is associated with lung cysts and spontaneous pneumothorax. The possibility of FLCN haploinsufficiency in pleural mesothelial cells (PMCs) contributing to development of pneumothorax has not yet been clarified. Electron microscopy revealed exposed intercellular boundaries between PMCs on visceral pleura and decreased electron density around the adherens junctions in BHDS. To characterize cellular function of PMCs in BHDS patients (BHDS-PMCs), during surgery for pneumothorax, we established the flow cytometry-based methods of isolating high-purity PMCs from pleural lavage fluid. BHDS-PMCs showed impaired cell attachment and a significant decrease in proliferation and migration, but a significant increase in apoptosis compared with PMCs from primary spontaneous pneumothorax (PSP) patients (PSP-PMCs). Microarray analysis using isolated PMCs revealed a significant alteration in the expression of genes belonging to Gene Ontology terms “cell–cell adhesion junction” and “cell adhesion molecule binding”. Gene set enrichment analysis demonstrated that CDH1, encoding E-cadherin, was identified in the down-regulated leading edge of a plot in BHDS-PMCs. AMPK and LKB1 activation were significantly impaired in BHDS-PMCs compared with PSP-PMCs. Our findings indicate that FLCN haploinsufficiency may affect the E-cadherin-LKB1-AMPK axis and lead to abnormal cellular function in BHDS-PMCs.
Unravelling the fatty acid profiles of different polychaete species cultured under integrated multi-trophic aquaculture (IMTA)
Authors: Jerónimo Daniel , Lillebø Ana Isabel , Maciel Elisabete , Domingues M. Rosário M. , Cremades Javier , Calado Ricardo 
Published: May 2021

AbstractPolychaetes can be successfully employed to recover otherwise wasted nutrients present in particulate organic matter (POM) of aquaculture effluents. The present study describes the fatty acid (FA) profile of four different polychaete species cultured in sand filters supplied with effluent water from a marine fish farm. The FA profile of cultured and wild Hediste diversicolor was compared and revealed a ≈ 24.2% dissimilarity, with cultured biomass displaying a higher content in two essential n-3 highly unsaturated FA (HUFA) (EPA [20:5 n-3] and DHA [22:6 n-3]—eicosapentaenoic and docosahexaenoic acid, respectively). The comparison of the FA profile of cultured H. diversicolor with that of other polychaete species whose larvae successfully settled on the sand filters (Diopatra neapolitana, Sabella cf. pavonina and Terebella lapidaria) revealed that their FA profile, which is here described for the first time, displayed high levels of EPA and DHA (≈ 1.5–4.8 and 1.0–1.1 µg mg−1 DW, respectively). The highest concentration of total FA per biomass of polychaete was recorded in H. diversicolor and T. lapidaria, with both species being the ones whose FA profiles revealed a lowest level of dissimilarity and more closely resembled that of the aquafeed used in the fish farm. In the present work it was demonstrated that it is possible to produce polychaetes biomass with high nutritional value through an eco-design concept such as integrated multi-trophic aquaculture (IMTA). Indeed, this framework promotes a cleaner production and, in this specific case, allowed to recover essential fatty acids that are commonly wasted in aquaculture effluents.
Estimates of gene ensemble noise highlight critical pathways and predict disease severity in H1N1, COVID-19 and mortality in sepsis patients
Authors: de Jong Tristan V. , Guryev Victor , Moshkin Yuri M. 
Published: May 2021

AbstractFinding novel biomarkers for human pathologies and predicting clinical outcomes for patients is challenging. This stems from the heterogeneous response of individuals to disease and is reflected in the inter-individual variability of gene expression responses that obscures differential gene expression analysis. Here, we developed an alternative approach that could be applied to dissect the disease-associated molecular changes. We define gene ensemble noise as a measure that represents a variance for a collection of genes encoding for either members of known biological pathways or subunits of annotated protein complexes and calculated within an individual. The gene ensemble noise allows for the holistic identification and interpretation of gene expression disbalance on the level of gene networks and systems. By comparing gene expression data from COVID-19, H1N1, and sepsis patients we identified common disturbances in a number of pathways and protein complexes relevant to the sepsis pathology. Among others, these include the mitochondrial respiratory chain complex I and peroxisomes. This suggests a Warburg effect and oxidative stress as common hallmarks of the immune host–pathogen response. Finally, we showed that gene ensemble noise could successfully be applied for the prediction of clinical outcome namely, the mortality of patients. Thus, we conclude that gene ensemble noise represents a promising approach for the investigation of molecular mechanisms of pathology through a prism of alterations in the coherent expression of gene circuits.
Antibiofilm and antivirulence potential of silver nanoparticles against multidrug-resistant Acinetobacter baumannii
Authors: Hetta Helal F. , Al-Kadmy Israa M. S. , Khazaal Saba Saadoon , Abbas Suhad , Suhail Ahmed , El-Mokhtar Mohamed A. , Ellah Noura H. Abd , Ahmed Esraa A. , Abd-ellatief Rasha B. , El-Masry Eman A. , Batiha Gaber El-Saber , Elkady Azza A. , Mohamed Nahed A. , Algammal Abdelazeem M. 
Published: May 2021

AbstractWe aimed to isolate Acinetobacter baumannii (A. baumannii) from wound infections, determine their resistance and virulence profile, and assess the impact of Silver nanoparticles (AgNPs) on the bacterial growth, virulence and biofilm-related gene expression. AgNPs were synthesized and characterized using TEM, XRD and FTIR spectroscopy. A. baumannii (n = 200) were isolated and identified. Resistance pattern was determined and virulence genes (afa/draBC, cnf1, cnf2, csgA, cvaC, fimH, fyuA, ibeA, iutA, kpsMT II, PAI, papC, PapG II, III, sfa/focDE and traT) were screened using PCR. Biofilm formation was evaluated using Microtiter plate method. Then, the antimicrobial activity of AgNPs was evaluated by the well-diffusion method, growth kinetics and MIC determination. Inhibition of biofilm formation and the ability to disperse biofilms in exposure to AgNPs were evaluated. The effect of AgNPs on the expression of virulence and biofilm-related genes (bap, OmpA, abaI, csuA/B, A1S_2091, A1S_1510, A1S_0690, A1S_0114) were estimated using QRT-PCR. In vitro infection model for analyzing the antibacterial activity of AgNPs was done using a co-culture infection model of A. baumannii with human fibroblast skin cell line HFF-1 or Vero cell lines. A. baumannii had high level of resistance to antibiotics. Most of the isolates harbored the fimH, afa/draBC, cnf1, csgA and cnf2, and the majority of A. baumannii produced strong biofilms. AgNPs inhibited the growth of A. baumannii efficiently with MIC ranging from 4 to 25 µg/ml. A. baumannii showed a reduced growth rate in the presence of AgNPs. The inhibitory activity and the anti-biofilm activity of AgNPs were more pronounced against the weak biofilm producers. Moreover, AgNPs decreased the expression of kpsMII , afa/draBC,bap, OmpA, and csuA/B genes. The in vitro infection model revealed a significant antibacterial activity of AgNPs against extracellular and intracellular A. baumannii. AgNPs highly interrupted bacterial multiplication and biofilm formation. AgNPs downregulated the transcription level of important virulence and biofilm-related genes. Our findings provide an additional step towards understanding the mechanisms by which sliver nanoparticles interfere with the microbial spread and persistence.