bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation Algorithm of Incident Sources' Stokes Parameters and 2‐D DOAs Based on Reduced Mutual Coupling Vector Sensor
Authors: Tao Jianwu , Yang Cheng‐zhi , Xu Cheng‐wei 
Published: August 2019

AbstractTo estimate Stokes parameters and two‐dimensional (2‐D) direction‐of‐arrival (DOA) of incident sources, a computational efficient algorithm is proposed based on reduced mutual coupling vector sensor. The biquaternion‐based output model of reduced mutual coupling vector sensor is presented. The contribution in this paper is mainly on the estimation of Stokes parameters. By exploiting the information in both the covariance matrix and the pseudo‐covariance matrix of the biquaternion‐based sensor's output, the Stokes parameters and 2‐D DOAs of partially polarized source can be extracted in closed form. Comparing with the Jone's formulation, the Stokes' formulation can characterize both completely polarized waves and partially polarized waves. Thus, the proposed algorithm is also applicable to completely polarized source. Because the proposed algorithm presents in closed form and does not require the search or iterative process, it is computationally more efficient. Simulations are used to verify the performance of the proposed algorithm.
Autophagy inhibition-mediated epithelial–mesenchymal transition augments local myofibroblast differentiation in pulmonary fibrosis
Authors: Hill Charlotte , Li Juanjuan , Liu Dian , Conforti Franco , Brereton Christopher J. , Yao Liudi , Zhou Yilu , Alzetani Aiman , Chee Serena J. , Marshall Ben G. , Fletcher Sophie V. , Hancock David , Ottensmeier Christian H. , Steele Andrew J. , Downward Julian , Richeldi Luca , Lu Xin , Davies Donna E. , Jones Mark G. , Wang Yihua 
Published: August 2019

AbstractIdiopathic pulmonary fibrosis (IPF), the prototypic progressive fibrotic interstitial lung disease, is thought to be a consequence of repetitive micro-injuries to an ageing, susceptible alveolar epithelium. Ageing is a risk factor for IPF and incidence has been demonstrated to increase with age. Decreased (macro)autophagy with age has been reported extensively in a variety of systems and diseases, including IPF. However, it is undetermined whether the role of faulty autophagy is causal or coincidental in the context of IPF. Here, we report that in alveolar epithelial cells inhibition of autophagy promotes epithelial–mesenchymal transition (EMT), a process implicated in embryonic development, wound healing, cancer metastasis and fibrosis. We further demonstrate that this is attained, at least in part, by increased p62/SQSTM1 expression that promotes p65/RELA mediated-transactivation of an EMT transcription factor, Snail2 (SNAI2), which not only controls EMT but also regulates the production of locally acting profibrogenic mediators. Our data suggest that reduced autophagy induces EMT of alveolar epithelial cells and can contribute to fibrosis via aberrant epithelial–fibroblast crosstalk.
Quantitative fermentation of unpretreated transgenic poplar by Caldicellulosiruptor bescii
Authors: Straub Christopher T. , Khatibi Piyum A. , Wang Jack P. , Conway Jonathan M. , Williams-Rhaesa Amanda M. , Peszlen Ilona M. , Chiang Vincent L. , Adams Michael W. W. , Kelly Robert M. 
Published: August 2019

AbstractMicrobial fermentation of lignocellulosic biomass to produce industrial chemicals is exacerbated by the recalcitrant network of lignin, cellulose and hemicelluloses comprising the plant secondary cell wall. In this study, we show that transgenic poplar (Populus trichocarpa) lines can be solubilized without any pretreatment by the extreme thermophile Caldicellulosiruptor bescii that has been metabolically engineered to shift its fermentation products away from inhibitory organic acids to ethanol. Carbohydrate solubilization and conversion of unpretreated milled biomass is nearly 90% for two transgenic lines, compared to only 25% for wild-type poplar. Unexpectedly, unpretreated intact poplar stems achieved nearly 70% of the fermentation production observed with milled poplar as the substrate. The nearly quantitative microbial conversion of the carbohydrate content of unpretreated transgenic lignocellulosic biomass bodes well for full utilization of renewable biomass feedstocks.
Allele specific repair of splicing mutations in cystic fibrosis through AsCas12a genome editing
Authors: Maule Giulia , Casini Antonio , Montagna Claudia , Ramalho Anabela S. , De Boeck Kris , Debyser Zeger , Carlon Marianne S. , Petris Gianluca , Cereseto Anna 
Published: August 2019

AbstractCystic fibrosis (CF) is an autosomal recessive disease caused by mutations in theCFTR gene. The 3272–26A>G and 3849+10kbC>TCFTRmutations alter the correct splicing of theCFTRgene, generating new acceptor and donor splice sites respectively. Here we develop a genome editing approach to permanently correct these genetic defects, using a single crRNA and theAcidaminococcus sp. BV3L6, AsCas12a. This genetic repair strategy is highly precise, showing very strong discrimination between the wild-type and mutant sequence and a complete absence of detectable off-targets. The efficacy of this gene correction strategy is verified in intestinal organoids and airway epithelial cells derived from CF patients carrying the 3272–26A>G or 3849+10kbC>T mutations, showing efficient repair and complete functional recovery of the CFTR channel. These results demonstrate that allele-specific genome editing with AsCas12a can correct aberrantCFTRsplicing mutations, paving the way for a permanent splicing correction in genetic diseases.
Supramolecular trap for catching polyamines in cells as an anti-tumor strategy
Authors: Chen Junyi , Ni Hanzhi , Meng Zhao , Wang Jing , Huang Xiayang , Dong Yansheng , Sun Chao , Zhang Yadan , Cui Lei , Li Jian , Jia Xueshun , Meng Qingbin , Li Chunju 
Published: August 2019

AbstractPolyamines are essential for the growth of eukaryotic cells and can be dysregulated in tumors. Here we describe a strategy to deplete polyamines through host–guest encapsulation using a peptide-pillar[5]arene conjugate (P1P5A, P1 = RGDSK(N3)EEEE) as a supramolecular trap. The RGD in the peptide sequence allows the molecule to bind to integrin αvβ3-overexpressing tumor cells. The negative charged glutamic acid residues enhance the inclusion affinities between the pillar[5]arene and cationic polyamines via electrostatic interactions and facilitate the solubility of the conjugate in aqueous media. The trap P1P5A efficiently encapsulates polyamines with association constants of 105–106 M−1. We show that P1P5A has a wide spectrum of antitumor activities, and induces apoptosis via affecting the polyamine biosynthetic pathway. Experiments in vivo show that P1P5A effectively inhibits the growth of breast adenocarcinoma xenografts in female nude mice. This work reveals an approach for suppressing tumor growth by using supramolecular macrocycles to trap polyamines in tumor cells.
Origin of nanoscale heterogeneity in the surface oxide film protecting stainless steel against corrosion
Authors: Ma Li , Wiame Frédéric , Maurice Vincent , Marcus Philippe 
Published: August 2019

AbstractStainless steels are widely used as metal components owing to self-protection in aggressive environments, provided by an extremely thin surface oxide film enriched in chromium oxide. Yet, despite decades of research, the mechanisms distributing the chromium enrichment at small length scale are poorly understood, although it may cause loss of stability and local failure of the corrosion resistance. Here, we apply high resolution surface analysis to investigate at small time and length scales the nucleation and growth mechanisms of the surface oxide on a model stainless steel. Starting from an oxide-free surface, we report the direct observation of the oxide nucleation and local oxidation of chromium, which governs the nanoscale heterogeneity of the growing surface oxide by chromium pumping from the atomic terraces to the steps for preferential Cr(III) oxide nucleation and subsequently by segregation from the atomic planes below to grow the Cr(III) layer incompletely saturating the stainless steel surface. This work provides new insight on corrosion chemistry, by evidencing local chemical and structural defects self-generated at the nanoscale by the building process of the protective oxide barrier, and affecting the passive film stability.
MRI of Whole Rat Brain Perivascular Network Reveals Role for Ventricles in Brain Waste Clearance
Authors: Magdoom Kulam Najmudeen , Brown Alec , Rey Julian , Mareci Thomas H. , King Michael A. , Sarntinoranont Malisa 
Published: August 2019

AbstractInvestigating the mechanisms by which metabolic wastes are cleared from nervous tissue is important for understanding natural function and the pathophysiology of several neurological disorders including Alzheimer’s disease. Recent evidence suggests clearance may be the function of annular spaces around cerebral blood vessels, called perivascular spaces (PVS), through which cerebrospinal fluid (CSF) is transported from the subarachnoid space into brain parenchyma to exchange with interstitial fluid (also known as the glymphatic system). In this work, an MRI-based methodology was developed to reconstruct the PVS network in whole rat brain to better elucidate both PVS uptake and clearance pathways. MR visible tracer (Gd-albumin) was infused in vivo into the CSF-filled lateral ventricle followed by ex vivo high-resolution MR imaging at 17.6 T with an image voxel volume two orders of magnitude smaller than previously reported. Imaged tracer distribution patterns were reconstructed to obtain a more complete brain PVS network. Several PVS connections were repeatedly highlighted across different animals, and new PVS connections between ventricles and different parts of the brain parenchyma were revealed suggesting a possible role for the ventricles as a source or sink for solutes in the brain. In the future, this methodology may be applied to understand changes in the PVS network with disease.
C mobilisation in disturbed tropical peat swamps: old DOC can fuel the fluvial efflux of old carbon dioxide, but site recovery can occur
Authors: Waldron Susan , Vihermaa Leena , Evers Stephanie , Garnett Mark H. , Newton Jason , Henderson Andrew C. G. 
Published: August 2019

AbstractSoutheast-Asian peat swamp forests have been significantly logged and converted to plantation. Recently, to mitigate land degradation and C losses, some areas have been left to regenerate. Understanding how such complex land use change affects greenhouse gas emissions is essential for modelling climate feedbacks and supporting land management decisions. We carried out field research in a Malaysian swamp forest and an oil palm plantation to understand how clear-felling, drainage, and illegal and authorized conversion to oil palm impacted the C cycle, and how the C cycle may change if such logging and conversion stopped. We found that both the swamp forest and the plantation emit centuries-old CO2 from their drainage systems in the managed areas, releasing sequestered C to the atmosphere. Oil palm plantations are an iconic symbol of tropical peatland degradation, but CO2 efflux from the recently-burnt, cleared swamp forest was as old as from the oil palm plantation. However, in the swamp forest site, where logging had ceased approximately 30 years ago, the age of the CO2 efflux was modern, indicating recovery of the system can occur. 14C dating of the C pool acted as a tracer of recovery as well as degradation and offers a new tool to assess efficacy of restoration management. Methane was present in many sites, and in higher concentrations in slow-flowing anoxic systems as degassing mechanisms are not strong. Methane loading in freshwaters is rarely considered, but this may be an important C pool in restored drainage channels and should be considered in C budgets and losses.
Association between dynamic resting-state functional connectivity and ketamine plasma levels in visual processing networks
Authors: Spies Marie , Klöbl Manfred , Höflich Anna , Hummer Allan , Vanicek Thomas , Michenthaler Paul , Kranz Georg S. , Hahn Andreas , Winkler Dietmar , Windischberger Christian , Kasper Siegfried , Lanzenberger Rupert 
Published: August 2019

AbstractNumerous studies demonstrate ketamine’s influence on resting-state functional connectivity (rsFC). Seed-based and static rsFC estimation methods may oversimplify FC. These limitations can be addressed with whole-brain, dynamic rsFC estimation methods. We assessed data from 27 healthy subjects who underwent two 3 T resting-state fMRI scans, once under subanesthetic, intravenous esketamine and once under placebo, in a randomized, cross-over manner. We aimed to isolate only highly robust effects of esketamine on dynamic rsFC by using eight complementary methodologies derived from two dynamic rsFC estimation methods, two functionally defined atlases and two statistical measures. All combinations revealed a negative influence of esketamine on dynamic rsFC within the left visual network and inter-hemispherically between visual networks (p < 0.05, corrected), hereby suggesting that esketamine’s influence on dynamic rsFC is highly stable in visual processing networks. Our findings may be reflective of ketamine’s role as a model for psychosis, a disorder associated with alterations to visual processing and impaired inter-hemispheric connectivity. Ketamine is a highly effective antidepressant and studies have shown changes to sensory processing in depression. Dynamic rsFC in sensory processing networks might be a promising target for future investigations of ketamine’s antidepressant properties. Mechanistically, sensitivity of visual networks for esketamine’s effects may result from their high expression of NMDA-receptors.
Plumbagin-induced oxidative stress leads to inhibition of Na+/K+-ATPase (NKA) in canine cancer cells
Authors: Alharbi Yousef , Kapur Arvinder , Felder Mildred , Barroilhet Lisa , Stein Timothy , Pattnaik Bikash R. , Patankar Manish S. 
Published: August 2019

AbstractThe Na+/K+-ATPase (NKA) complex is the master regulator of membrane potential and a target for anti-cancer therapies. Here, we investigate the effect of drug-induced oxidative stress on NKA activity. The natural product, plumbagin increases oxygen radicals through inhibition of oxidative phosphorylation. As a result, plumbagin treatment results in decreased production of ATP and a rapid increase in intracellular oxygen radicals. We show that plumbagin induces apoptosis in canine cancer cells via oxidative stress. We use this model to test the effect of oxidative stress on NKA activity. Using whole-cell patch-clamp electrophysiology we demonstrate that short-term exposure (4 min) to plumbagin results in 48% decrease in outward current at +50 mV. Even when exogenous ATP was supplied to the cells, plumbagin treatment resulted in 46% inhibition of outward current through NKA at +50 mV. In contrast, when the canine cancer cells were pre-treated with the oxygen radical scavenger, N-acetylcysteine, the NKA inhibitory activity of plumbagin was abrogated. These experiments demonstrate that the oxidative stress-causing agents such as plumbagin and its analogues, are a novel avenue to regulate NKA activity in tumors.
Exploitation may influence the climate resilience of fish populations through removing high performance metabolic phenotypes
Authors: Duncan Murray I. , Bates Amanda E. , James Nicola C. , Potts Warren M. 
Published: August 2019

AbstractPhysiological rates and processes underpin the relationships between ectothermic organisms, such as fish, and their environment. The response and persistence of fish populations in an increasingly variable ocean is dependent on the distribution and diversity of physiological phenotypes. Growing evidence suggests that fisheries exploitation can selectively target certain physiological and behavioural phenotypes, which may shift exploited populations to altered physiological states. Here we test if commercial fisheries have the potential to do this in a “natural laboratory” along the South African coast. We compare metabolic traits of exploited and protected populations of the fish species, Chrysoblephus laticeps, which is a major component of the South African hook and line fishery. We find that high-performance aerobic scope phenotypes are reduced in the fished population. The most likely mechanism for this finding is a positive relationship between aerobic scope and capture vulnerability in passive-gear fisheries. Our results further highlight the selective nature of capture-fisheries and suggest that exploitation has the capacity to alter climate responses of fish populations on a physiological level. Our finding also implicates how Marine Protected Areas, through harbouring individuals with a greater diversity of physiological traits, may provide greater fish response diversity to environmental variability.
Endoplasmic reticulum stress disrupts lysosomal homeostasis and induces blockade of autophagic flux in human trophoblasts
Authors: Nakashima Akitoshi , Cheng Shi-Bin , Kusabiraki Tae , Motomura Kenichiro , Aoki Aiko , Ushijima Akemi , Ono Yosuke , Tsuda Sayaka , Shima Tomoko , Yoshino Osamu , Sago Haruhiko , Matsumoto Kenji , Sharma Surendra , Saito Shigeru 
Published: August 2019

AbstractPregnancy is a stress factor culminating into mild endoplasmic reticulum (ER) stress, which is necessary for placental development. However, excessive or chronic ER stress in pre-eclamptic placentas leads to placental dysfunction. The precise mechanisms through which excessive ER stress impacts trophoblasts are not well understood. Here, we showed that ER stress reduces the number of lysosomes, resulting in inhibition of autophagic flux in trophoblast cells. ER stress also disrupted the translocation of lysosomes to the surface of trophoblast cells, and inhibited lysosomal exocytosis, whereby the secretion of lysosomal-associated membrane protein 1 (LAMP1) into culture media was significantly attenuated. In addition, we found that serum LAMP1 and beta-galactosidase levels were significantly decreased in pre-eclampsia patients compared to normal pregnant women, potentially indicating lysosomal dysfunction through ER stress in pre-eclamptic placentas. Thus, we demonstrated that excessive ER stress essentially disrupts homeostasis in trophoblasts in conjunction with autophagy inhibition by lysosomal impairment.
The commensal Escherichia coli CEC15 reinforces intestinal defences in gnotobiotic mice and is protective in a chronic colitis mouse model
Authors: Escribano-Vazquez Unai , Verstraeten Sophie , Martin Rebeca , Chain Florian , Langella Philippe , Thomas Muriel , Cherbuy Claire 
Published: August 2019

AbstractEscherichia coli is a regular inhabitant of the gut microbiota throughout life. However, its role in gut health is controversial. Here, we investigated the relationship between the commensal E. coli strain CEC15 (CEC), which we previously isolated, and the intestine in homeostatic and disease-prone settings. The impact of CEC was compared to that of the probiotic E. coli Nissle 1917 (Nissle) strain. The expression of ileal and colonic genes that play a key role in intestinal homeostasis was higher in CEC- and Nissle-mono-associated wild-type mice than in germfree mice. This included genes involved in the turnover of reactive oxygen species, antimicrobial peptide synthesis, and immune responses. The impact of CEC and Nissle on such gene expression was stronger in a disease-prone setting, i.e. in gnotobiotic IL10-deficient mice. In a chronic colitis model, CEC more strongly decreased signs of colitis severity (myeloperoxidase activity and CD3+ immune-cell infiltration) than Nissle. Thus, our study shows that CEC and Nissle contribute to increased expression of genes involved in the maintenance of gut homeostasis in homeostatic and inflammatory settings. We show that these E. coli strains, in particular CEC, can have a beneficial effect in a chronic colitis mouse model.
The potential role of scavengers in spreading African swine fever among wild boar
Authors: Probst Carolina , Gethmann Jörn , Amler Susanne , Globig Anja , Knoll Bent , Conraths Franz J. 
Published: August 2019

AbstractUnderstanding the transmission patterns of African swine fever (ASF) among wild boar (Sus scrofa) is an issue of major interest, especially in the wake of the current ASF epidemic. Given the high stability of ASF-virus, there is concern about scavengers spreading infectious carcass material in the environment. Here, we describe scavenging activities on 32 wild boar carcasses in their natural habitat in Germany. Using digital cameras, we detected 22 vertebrates at the study sites, thereof two mammal and three bird species scavenging. The most frequently detected species was the raccoon dog Nyctereutes procyonoides (44% of all visits). Raccoon dogs, red foxes (Vulpes vulpes), and buzzards (Buteo buteo) scavenged in the warm and the cold season, while ravens (Corvus corax) and white-tailed eagles (Haliaeetus albicilla) scavenged only in the cold season. In summer, however, insects removed most of the carcass biomass. Although most of the material was consumed on the spot, foxes, raccoon dogs and ravens left the study sites in rare cases with a small piece of meat in their mouths or beaks. We conclude that scavengers represent a minor risk factor for spreading ASF, but may contribute to reducing local virus persistence by metabolizing infected carcasses.
Ensilication Improves the Thermal Stability of the Tuberculosis Antigen Ag85b and an Sbi-Ag85b Vaccine Conjugate
Authors: Wahid A. A. , Doekhie A. , Sartbaeva A. , van den Elsen J. M. H 
Published: August 2019

AbstractThere is an urgent need for the development of vaccine thermostabilisation methodologies as the maintenance of a continuous and reliable cold chain remains a major hurdle to the global distribution of safe and effective vaccines. Ensilication, a method that encases proteins in a resistant silica cage has been shown to physically prevent the thermal denaturation of a number of model proteins. In this study we investigate the utility of this promising approach in improving the thermal stability of antigens and vaccine conjugates highly relevant to the development of candidate tuberculosis vaccines, including antigen 85b conjugated with theStaphylococcus aureus-protein based adjuvant Sbi. Here we analyse the sensitivity of these constructs to thermal denaturation and demonstrate for the first time the benefits of ensilication in conferring these vaccine-relevant proteins with protection against temperature-induced loss of structure and function without the need for refrigeration. Our results reveal the potential of ensilication in facilitating the storage and transport of vaccines at ambient temperatures in the future and therefore in delivering life-saving vaccines globally, and in particular to remote areas of developing countries where disease rates are often highest.