bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune lymphocytes halt replication of Francisella tularensis LVS within the cytoplasm of infected macrophages
Authors: Bradford Mary Katherine , Elkins Karen L. 
Published: July 2020

AbstractFrancisella tularensisis a highly infectious intracellular bacterium that causes tularemia by invading and replicating in mammalian myeloid cells.Francisellaprimarily invades host macrophages, where it escapes phagosomes within a few hours and replicates in the cytoplasm. Less is known about howFrancisellatraffics within macrophages or exits into the extracellular environment for further infection. Immune T lymphocytes control the replication ofFrancisellawithin macrophages in vitro by a variety of mechanisms, but nothing is known about intracellular bacterial trafficking in the face of such immune pressure. Here we used a murine model of infection with aFrancisellaattenuated live vaccine strain (LVS), which is under study as a human vaccine, to evaluate the hypothesis that immune T cells control intramacrophage bacterial growth by re-directing bacteria into toxic intracellular compartments of infected macrophages. We visualized the interactions of lymphocytes and LVS-infected macrophages using confocal microscopy and characterized LVS intramacrophage trafficking when co-cultured with immune lymphocytes. We focused on the late stages of infection after bacteria escape from phagosomes, through bacterial replication and the death of macrophages. We found that the majority of LVS remained cytosolic in the absence of immune pressure, eventually resulting in macrophage death. In contrast, co-culture of LVS-infected macrophages with LVS-immune lymphocytes halted LVS replication and inhibited the spread of LVS infection between macrophages, but bacteria did not return to vacuoles such as lysosomes or autophagosomes and macrophages did not die. Therefore, immune lymphocytes directly limit intracellular bacterial replication within the cytoplasm of infected macrophages.
Mechanically driven strategies to improve electromechanical behaviour of printed stretchable electronic systems
Authors: Di Vito Donato , Mosallaei Milad , Khorramdel Behnam , Kanerva Mikko , Mäntysalo Matti 
Published: July 2020

AbstractStretchable electronics promise to extend the application range of conventional electronics by enabling them to keep their electrical functionalities under system deformation. Within this framework, development of printable silver-polymer composite inks is making possible to realize several of the expected applications for stretchable electronics, which range from seamless sensors for human body measurement (e.g. health patches) to conformable injection moulded structural electronics. However, small rigid electric components are often incorporated in these devices to ensure functionality. Under mechanical loading, these rigid elements cause strain concentrations and a general deterioration of the system’s electrical performance. This work focuses on different strategies to improve electromechanical performance by investigating the deformation behaviour of soft electronic systems comprising rigid devices through Finite Element analyses. Based on the deformation behaviour of a simple stretchable device under tensile loading, three general strategies were proposed: local component encapsulation, direct component shielding, and strain dispersion. The FE behaviour achieved using these strategies was then compared with the experimental results obtained for each design, highlighting the reasons for their different resistance build-up. Furthermore, crack formation in the conductive tracks was analysed under loading to highlight its link with the evolution of the system electrical performance.
Selective protection of human cardiomyocytes from anthracycline cardiotoxicity by small molecule inhibitors of MAP4K4
Authors: Golforoush Pelin A. , Narasimhan Priyanka , Chaves-Guerrero Patricia P. , Lawrence Elsa , Newton Gary , Yan Robert , Harding Sian E. , Perrior Trevor , Chapman Kathryn L. , Schneider Michael D. 
Published: July 2020

AbstractGiven the poor track record to date of animal models for creating cardioprotective drugs, human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have been proposed as a therapeutically relevant human platform to guide target validation and cardiac drug development. Mitogen-Activated Protein Kinase Kinase Kinase Kinase-4 (MAP4K4) is an “upstream” member of the MAPK superfamily that is implicated in human cardiac muscle cell death from oxidative stress, based on gene silencing and pharmacological inhibition in hPSC-CMs. A further role for MAP4K4 was proposed in heart muscle cell death triggered by cardiotoxic anti-cancer drugs, given its reported activation in failing human hearts with doxorubicin (DOX) cardiomyopathy, and its activation acutely by DOX in cultured cardiomyocytes. Here, we report successful protection from DOX in two independent hPSC-CM lines, using two potent, highly selective MAP4K4 inhibitors. The MAP4K4 inhibitors enhanced viability and reduced apoptosis at otherwise lethal concentrations of DOX, and preserved cardiomyocyte function, as measured by spontaneous calcium transients, at sub-maximal ones. Notably, in contrast, no intereference was seen in tumor cell killing, caspase activation, or mitochondrial membrane dissipation by DOX, in human cancer cell lines. Thus, MAP4K4 is a plausible, tractable, selective therapeutic target in DOX-induced human heart muscle cell death.
Functional and morphological cardiovascular alterations associated with neurofibromatosis 1
Authors: Cutruzzolà Antonio , Irace Concetta , Frazzetto Marco , Sabatino Jolanda , Gullace Rosa , De Rosa Salvatore , Spaccarotella Carmen , Concolino Daniela , Indolfi Ciro , Gnasso Agostino 
Published: July 2020

AbstractSubjects with Neurofibromatosis 1 (NF1) develop vascular complications. The protein product of the gene affected in NF1, neurofibromin, physiologically modulates endothelial function and preserves vascular and myocardial structure. Our study aimed to verify whether subjects with NF1 have early, preclinical abnormalities of carotid artery structure, brachial artery function, and cardiac function. We recruited 22 NF1 subjects without previous cardiovascular events and 22 healthy control subjects. All subjects underwent measurement of carotid artery intima-media thickness (IMT), evaluation of brachial artery endothelial function after ischemia and exercise, and cardiac function. Mean IMT was 543 ± 115 μ in NF1 subjects and 487 ± 70 μ in Controls (p < 0.01). Endothelial function was significantly dumped in NF1 subjects. The dilation after ischemia and exercise was respectively 7.5(± 4.8)% and 6.7(± 3.0)% in NF1 versus 10.5(± 1.2)% and 10.5(± 2.1)% in control subjects (p < 0.02; p < 0.002). Left ventricular systolic function assessed by Global Longitudinal Strain was significantly different between NF1 subjects and Controls: − 19.3(± 1.7)% versus − 21.5(± 2.7)% (p < 0.008). These findings demonstrate that NF1 patients have early morphological and functional abnormalities of peripheral arteries and systolic cardiac impairment and suggest the need for a tight cardiovascular risk evaluation and primary prevention in subjects with NF1.
Cardanol derived P, Si and N based precursors to develop flame retardant phenolic foam
Authors: Bo Caiying , Shi Zhongyu , Hu Lihong , Pan Zheng , Hu Yun , Yang Xiaohui , Jia Puyou , Ren Xiaoli , Zhang Meng , Zhou Yonghong 
Published: July 2020

AbstractA novel eco-friendly halogen-free cardanol-based flame retardant with P, Si, and N on the chain backbone (PSNCFR) was synthesized and incorporated into phenolic foams (PFs). PSNCFR was comprehensively investigated via Fourier transform infrared spectroscopy and nuclear magnetic resonance. PSNCFR endowed PFs with flame retardancy, contributed to generating a composite char defense against flames, and efficiently prevented smoking from PFs. PSNCFR introduction improved the flexural strength of the PFs to approximately 155% of that of pristine PF. PSNCFR-modified PFs displayed a high limiting oxygen index value of 41.9%. The results of cone calorimeter show that the mean heat release rate, mean effective heat of combustion, and total heat release of the PSNCFR-modified PFs reduced by 26.92%, 35.71%, and 31.25%, respectively. In particular, the total smoke production of the PSNCFR-modified PFs decreased by 64.55%, indicating excellent smoke inhibition. As for the mechanism, the condensation and gas phases during pyrolysis were responsible for the synergistic flame retardancy in the modified PFs. The findings demonstrate that PSNCFR can be used in PF preparation to overcome their drawbacks of internal brittleness and flammability.
Conservation of Cdc14 phosphatase specificity in plant fungal pathogens: implications for antifungal development
Authors: DeMarco Andrew G. , Milholland Kedric L. , Pendleton Amanda L. , Whitney John J. , Zhu Peipei , Wesenberg Daniel T. , Nambiar Monessha , Pepe Antonella , Paula Stefan , Chmielewski Jean , Wisecaver Jennifer H. , Tao W. Andy , Hall Mark C. 
Published: July 2020

AbstractCdc14 protein phosphatases play an important role in plant infection by several fungal pathogens. This and other properties of Cdc14 enzymes make them an intriguing target for development of new antifungal crop treatments. Active site architecture and substrate specificity of Cdc14 from the model fungusSaccharomyces cerevisiae(ScCdc14) are well-defined and unique among characterized phosphatases. Cdc14 appears absent from some model plants. However, the extent of conservation of Cdc14 sequence, structure, and specificity in fungal plant pathogens is unknown. We addressed this by performing a comprehensive phylogenetic analysis of the Cdc14 family and comparing the conservation of active site structure and specificity among a sampling of plant pathogen Cdc14 homologs. We show that Cdc14 was lost in the common ancestor of angiosperm plants but is ubiquitous in ascomycete and basidiomycete fungi. The unique substrate specificity of ScCdc14 was invariant in homologs from eight diverse species of dikarya, suggesting it is conserved across the lineage. A synthetic substrate mimetic inhibited diverse fungal Cdc14 homologs with similar low µMKivalues, but had little effect on related phosphatases. Our results justify future exploration of Cdc14 as a broad spectrum antifungal target for plant protection.
Structural and chemical evolution of Au-silica core–shell nanoparticles during 20 keV helium ion irradiation: a comparison between experiment and simulation
Authors: Mousley M. , Möller W. , Philipp P. , Hlawacek G. , Wirtz T. , Eswara S. 
Published: July 2020

AbstractAu-silica core–shell nanoparticles have been irradiated with 20 keV He+ ions up to a maximum fluence of 4.7 × 1017 ions/cm2. The nanoscale structural and crystallographic evolution induced by He+ ion irradiation was followed at various stages using Transmission Electron Microscopy (TEM). During irradiation satellite Au clusters are formed around the main Au core, which remained crystalline even after the maximum He+ ion fluence. The spherical silica shell deformed into a hemisphere due to He+ ion irradiation. Three dimensional Monte-Carlo simulations, based on the binary collision approximation, have been performed on stacked infinite layers and an individual particle. The stacked layers results show that the He+ beam interacts with most of the nanoparticle and Au migrates in the direction of beam incidence agreeing with experimental findings. The individual particle results match the experiment in terms of the volume which is sputtered away however additional mechanisms, not included in the simulations, are present in the experiment during the satellite formation and silica shell deformation. These results show the ability for 20 keV He+ ions to be used for the modification of nanostructures. Furthermore, these results contribute to a quantitative understanding of the dynamic evolution of materials observed using microscopy techniques based on He+ ions.
Cardio-postural interactions and muscle-pump baroreflex are severely impacted by 60-day bedrest immobilization
Authors: Xu Da , Tremblay Malcom F. , Verma Ajay K. , Tavakolian Kouhyar , Goswami Nandu , Blaber Andrew P. 
Published: July 2020

AbstractTo understand fundamental mechanisms associated with post-flight orthostatic intolerance we investigated the interaction between the cardiovascular and postural functions before and after 60 days of head down bedrest (HDBR). Twenty healthy young males (35.0 ± 1.7 years) were subjected to 60-day HDBR at 6˚ to simulate spaceflight-induced fluid shifts. A supine-to-stand (STS) test was conducted to evaluate cardio-postural control before and after (R) HDBR while an assessment of cardiovascular function was performed during HDBR. Beat-to-beat heart period, systolic blood pressure, and electromyography impulses were derived for wavelet transform coherence and causality analyses of the cardio-postural control and used to assess changes in the muscle-pump baroreflex. During quiet stand of the STS test, compared to baseline, heart rate was 50% higher on the day of exit from bedrest (R0) and 20% higher eight days later (R8). There was a 50% increase in deoxygenated hemoglobin on R0 and R8. Leg muscle activity reduced, and postural sway increased after HDBR. Causality of the muscle-pump baroreflex was reduced on R0 (0.73 ± 0.2) compared to baseline (0.87 ± 0.2) with complete recovery by R8. The muscle-pump baroreflex also had decreased gain and fraction time active following HDBR. Overall, our data show a significantly impaired muscle-pump baroreflex following bedrest.
Clinical and imaging features of intraosseous arteriovenous malformations in jaws: a 15-year experience of single centre
Authors: Li Xiao , Su Lixin , Wang Deming , Gui Zhipeng , Jiang Mengda , Yang Xitao , Han Yifeng , Zhang Liming , Zheng Lianzhou , Fan Xindong 
Published: July 2020

AbstractIntraosseous arteriovenous malformations in jaws (j-AVMs) are rare congenital high-flow vascular anomalies with a high tendency of life-threatening haemorrhage and are regarded as one of the most dangerous haemorrhagic diseases in maxillofacial region. Pre-treatment clinical and imaging evaluations serve as the most important diagnostic modalities. A retrospective study involved 211 patients with j-AVMs from November 2003 to November 2017 was performed. The male-to-female ratio of j-AVMs was approximately 4:3. The mean age of the patients with j-AVMs is 21.86. Bleeding was the main complaint associated with j-AVMs. J-AVMs occurred in the mandible more often than in the maxilla (64.93% and 32.23%, respectively). Most j-AVMs (95.26%) occurred in the posterior teeth region. Classical imaging features of j-AVMs included: an unclear maxillary sinus with a mild ground-glass appearance (maxillary j-AVMs) and a clear oval or irregular lucency that is mostly centred on the root of the first molar (mandibular j-AVMs) on OPGs, enhancement in the cancellous bone on contrast-enhanced CTs. Other atypical features of j-AVMs were also concluded. A comprehensive diagnose system based on clinical and imaging features of j-AVMs could provide valuable reference data for clinical management of j-AVMs and help avoid improper iatrogenic trauma or delayed treatment.
Differences in the insect fauna associated to a monocultural pasture and a silvopasture in Southeastern Brazil
Authors: Paiva Iris Guedes , Auad Alexander Machado , Veríssimo Bruno Antonio , Silveira Luís Cláudio Paterno 
Published: July 2020

AbstractA major challenge for global agriculture is the reduction of the environmental impacts caused by meat and dairy production, and the conversion of monocultural pastures to silvopastoral systems has emerged as an important ally in this process. In order to understand the effects of this conversion we analysed 4 years of sampling of the insect fauna from a conventional monocultural pasture and a silvopastoral system in Minas Gerais, Brazil. We aimed to determine whether the changes caused by the conversion affected the abundance, richness and diversity of the insect orders found in the two systems. Total abundance, richness and diversity did not differ between the two systems, but we detected a significant difference in community composition. Several insect orders showed differences in either abundance, richness or diversity between the two systems, and several families of Hymenoptera, which contains pollinators and natural enemies, showed important increases in the silvopasture. Conversion of monocultural pastures to silvopastures can have important consequences on insect fauna involved in essential ecosystem functions, and the implementation of silvopastures at larger scales has the potential to benefit biodiversity conservation and ecosystem service provision at the landscape scale.
TIMP-3 facilitates binding of target metalloproteinases to the endocytic receptor LRP-1 and promotes scavenging of MMP-1
Authors: Carreca Anna P. , Pravatà Veronica M. , Markham Matthew , Bonelli Simone , Murphy Gillian , Nagase Hideaki , Troeberg Linda , Scilabra Simone D. 
Published: July 2020

AbstractMatrix metalloproteinases (MMPs) and the related families of disintegrin metalloproteinases (ADAMs) and ADAMs with thrombospondin repeats (ADAMTSs) play a crucial role in extracellular matrix (ECM) turnover and shedding of cell-surface molecules. The proteolytic activity of metalloproteinases is post-translationally regulated by their endogenous inhibitors, known as tissue inhibitors of metalloproteinases (TIMPs). Several MMPs, ADAMTSs and TIMPs have been reported to be endocytosed by the low-density lipoprotein receptor-related protein-1 (LRP-1). Different binding affinities of these proteins for the endocytic receptor correlate with different turnover rates which, together with differences in their mRNA expression, determines their nett extracellular levels. In this study, we used surface plasmon resonance to evaluate the affinity between LRP-1 and a number of MMPs, ADAMs, ADAMTSs, TIMPs and metalloproteinase/TIMP complexes. This identified MMP-1 as a new LRP-1 ligand. Among the proteins analyzed, TIMP-3 bound to LRP-1 with highest affinity (KD = 1.68 nM). Additionally, we found that TIMP-3 can facilitate the clearance of its target metalloproteinases by bridging their binding to LRP-1. For example, the free form of MMP-1 was found to have a KD of 34.6 nM for LRP-1, while the MMP-1/TIMP-3 complex had a sevenfold higher affinity (KD = 4.96 nM) for the receptor. TIMP-3 similarly bridged binding of MMP-13 and MMP-14 to LRP-1. TIMP-1 and TIMP-2 were also found to increase the affinity of target metalloproteinases for LRP-1, albeit to a lesser extent. This suggests that LRP-1 scavenging of TIMP/metalloproteinase complexes may be a general mechanism by which inhibited metalloproteinases are removed from the extracellular environment.
Climatological influences on major storm events during the last millennium along the Atlantic coast of France
Authors: Pouzet Pierre , Maanan Mohamed 
Published: July 2020

AbstractThis paper reviews the climatological influences on major past storm events in the North-east Atlantic. Analyses are based on a millenary record of sedimentological and historical impacts affecting coastal societies. The effects of 20 past storms have been found from sedimentary deposits from the last 1,000 years. Historical archives confirmed these events. This paper highlights five major storms that have markedly impacted coastal populations. They date back to 1351–1352, 1469, 1645, 1711 and 1751 AD. The 1351–1352 AD event is defined as a millennium storm that was “likely apocalyptical”, provoking serious damage and long lasting floods on much of the European coast. Major storm impacts have mostly been recorded during positive North Atlantic Oscillation phases. Four decreasing temperature phases are concomitant with 1300–1355, 1420–1470, 1560–1590 and 1690–1715 AD periods, during which much of the northern Atlantic coast of France underwent severe storm damages.
Harmonizing hybridization dissonance in conservation
Authors: Quilodrán Claudio S. , Montoya-Burgos Juan I. , Currat Mathias 
Published: July 2020

AbstractA dramatic increase in the hybridization between historically allopatric species has been induced by human activities. However, the notion of hybridization seems to lack consistency in two respects. On the one hand, it is inconsistent with the biological species concept, which does not allow for interbreeding between species, and on the other hand, it is considered either as an evolutionary process leading to the emergence of new biodiversity or as a cause of biodiversity loss, with conservation implications. In the first case, we argue that conservation biology should avoid the discussion around the species concept and delimit priorities of conservation units based on the impact on biodiversity if taxa are lost. In the second case, we show that this is not a paradox but an intrinsic property of hybridization, which should be considered in conservation programmes. We propose a novel view of conservation guidelines, in which human-induced hybridization may also be a tool to enhance the likelihood of adaptation to changing environmental conditions or to increase the genetic diversity of taxa affected by inbreeding depression. The conservation guidelines presented here represent a guide for the development of programmes aimed at protecting biodiversity as a dynamic evolutionary system.
Organophosphorus zwitterions engaged in a conjugated macrocycle on fullerene
Authors: Hashikawa Yoshifumi , Okamoto Shu , Murata Yasujiro 
Published: July 2020

AbstractOrganophosphorus zwitterions are one of the most important but elusive intermediates for carbon–carbon bond formation in synthetic chemistry and biology. However, a lack of isolated examples due to their lability has hampered in-depth understanding of structures and their reaction mechanisms. In this study, we crystallographically reveal the solid-state structure of a phosha-Michael adduct engaged in a cage-opened C60 skeleton, which is formed as a kinetic product. This compound exhibits dark brown colour in solution with an intense absorption band that extends to 1000 nm, reflecting intramolecular charge transfer transitions. From the 1,2-dicarbonyl moiety on the conjugated orifice, β-oxo-phosphorus ylide is formed as a thermodynamic product. The reaction mechanism that has long been disputed is examined by experimental and theoretical studies, showing a pathway which includes an SN2 reaction as a key step instead of the hitherto considered carbene pathway.
Time-reversal of an unknown quantum state
Authors: Lebedev A. V. , Vinokur V. M. 
Published: July 2020

AbstractFor decades, researchers have sought to understand how the irreversibility of the surrounding world emerges from the seemingly time-symmetric, fundamental laws of physics. Quantum mechanics conjectured a clue that final irreversibility is set by the measurement procedure and that the time-reversal requires complex conjugation of the wave function, which is overly complex to spontaneously appear in nature. Building on this Landau-Wigner conjecture, it became possible to demonstrate that time-reversal is exponentially improbable in a virgin nature and to design an algorithm artificially reversing a time arrow for a given quantum state on the IBM quantum computer. However, the implemented arrow-of-time reversal embraced only the known states initially disentangled from the thermodynamic reservoir. Here we develop a procedure for reversing the temporal evolution of an arbitrary unknown quantum state. This opens the route for general universal algorithms sending temporal evolution of an arbitrary system backward in time.