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search.filters.applied.f.access: openAccess × End date: 2021 × Start date: 2020 × Has files: Yes × Subject: human ×

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    Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection
    (San Francisco, California, US : PLOS, 2021) Mohamed, Hager; Clemen, Ramona; Freund, Eric; Lackmann, Jan-Wilm; Wende, Kristian; Connors, Jennifer; Haddad, Elias K.; Dampier, Will; Wigdahl, Brian; Miller, Vandana; Bekeschus, Sander; Krebs, Fred C.; Kashanchi, Fatah
    Effective control of infection by human immunodeficiency virus type 1 (HIV-1), the causative agent of the acquired immunodeficiency syndrome (AIDS), requires continuous and life-long use of anti-retroviral therapy (ART) by people living with HIV-1 (PLWH). In the absence of ART, HIV-1 reemergence from latently infected cells is ineffectively suppressed due to suboptimal innate and cytotoxic T lymphocyte responses. However, ART-free control of HIV-1 infection may be possible if the inherent immunological deficiencies can be reversed or restored. Herein we present a novel approach for modulating the immune response to HIV-1 that involves the use of non-thermal plasma (NTP), which is an ionized gas containing various reactive oxygen and nitrogen species (RONS). J-Lat cells were used as a model of latent HIV-1 infection to assess the effects of NTP application on viral latency and the expression of pro-phagocytic and pro-chemotactic damage-associated molecular patterns (DAMPs). Exposure of J-Lat cells to NTP resulted in stimulation of HIV-1 gene expression, indicating a role in latency reversal, a necessary first step in inducing adaptive immune responses to viral antigens. This was accompanied by the release of pro-inflammatory cytokines and chemokines including interleukin-1β (IL-1β) and interferon-γ (IFN-γ); the display of pro-phagocytic markers calreticulin (CRT), heat shock proteins (HSP) 70 and 90; and a correlated increase in macrophage phagocytosis of NTP-exposed J-Lat cells. In addition, modulation of surface molecules that promote or inhibit antigen presentation was also observed, along with an altered array of displayed peptides on MHC I, further suggesting methods by which NTP may modify recognition and targeting of cells in latent HIV-1 infection. These studies represent early progress toward an effective NTP-based ex vivo immunotherapy to resolve the dysfunctions of the immune system that enable HIV-1 persistence in PLWH.
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    PDA Indolylmaleimides Induce Anti-Tumor Effects in Prostate Carcinoma Cell Lines Through Mitotic Death
    (Lausanne : Frontiers Research Foundation, 2021) Schille, Jan Torben; Nolte, Ingo; Beck, Julia; Jilani, Daria; Roolf, Catrin; Pews-Davtyan, Anahit; Rolfs, Arndt; Henze, Larissa; Beller, Matthias; Brenig, Bertram; Junghanss, Christian; Schütz, Ekkehard; Murua Escobar, Hugo
    Castrate resistant prostate cancer in men shares several characteristics with canine prostate cancer (PCa). Due to current insufficient therapies, evaluating novel therapeutic agents for late-stage PCa is of considerable interest for both species. PDA indolylmaleimides showed anticancer effects in several neoplastic cell lines. Herein, a comparative characterization of PDA-66 and PDA-377 mediated effects was performed in human and canine PCa cell lines, which is also the first detailed characterization of these agents on cells derived from solid tumors in general. While PDA-377 showed only weak growth inhibition on human PCa cell lines, PDA-66 inhibited proliferation and induced apoptosis in human and canine cell lines with concentrations in the low micromolar range. Morphological characterization and whole transcriptome sequencing revealed that PDA-66 induces mitotic death through its microtubule-depolymerizing ability. PDA-66 appears to be a worthwhile anti-mitotic agent for further evaluation. The similarities in cellular and molecular response observed in the cell lines of both origins form a solid basis for the use of canine PCa in vivo models to gain valuable interchangeable data to the advantage of both species.
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    Accurate in vivo tumor detection using plasmonic-enhanced shifted-excitation Raman difference spectroscopy (SERDS)
    (Wyoming, NSW : Ivyspring, 2021) Strobbia, Pietro; Cupil-Garcia, Vanessa; Crawford, Bridget M.; Fales, Andrew M.; Pfefer, T. Joshua; Liu, Yang; Maiwald, Martin; Sumpf, Bernd; Vo-Dinh, Tuan
    For the majority of cancer patients, surgery is the primary method of treatment. In these cases, accurately removing the entire tumor without harming surrounding tissue is critical; however, due to the lack of intraoperative imaging techniques, surgeons rely on visual and physical inspection to identify tumors. Surface-enhanced Raman scattering (SERS) is emerging as a non-invasive optical alternative for intraoperative tumor identification, with high accuracy and stability. However, Raman detection requires dark rooms to work, which is not consistent with surgical settings. Methods: Herein, we used SERS nanoprobes combined with shifted-excitation Raman difference spectroscopy (SERDS) detection, to accurately detect tumors in xenograft murine model. Results: We demonstrate for the first time the use of SERDS for in vivo tumor detection in a murine model under ambient light conditions. We compare traditional Raman detection with SERDS, showing that our method can improve sensitivity and accuracy for this task. Conclusion: Our results show that this method can be used to improve the accuracy and robustness of in vivo Raman/SERS biomedical application, aiding the process of clinical translation of these technologies. © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
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    Monsoon forced evolution of savanna and the spread of agro-pastoralism in peninsular India
    ([London] : Macmillan Publishers Limited, part of Springer Nature, 2021) Riedel, Nils; Fuller, Dorian Q.; Marwan, Norbert; Poretschkin, Constantin; Basavaiah, Nathani; Menzel, Philip; Ratnam, Jayashree; Prasad, Sushma; Sachse, Dirk; Sankaran, Mahesh; Sarkar, Saswati; Stebich, Martina
    An unresolved issue in the vegetation ecology of the Indian subcontinent is whether its savannas, characterized by relatively open formations of deciduous trees in C4-grass dominated understories, are natural or anthropogenic. Historically, these ecosystems have widely been regarded as anthropogenic-derived, degraded descendants of deciduous forests. Despite recent work showing that modern savannas in the subcontinent fall within established bioclimatic envelopes of extant savannas elsewhere, the debate persists, at least in part because the regions where savannas occur also have a long history of human presence and habitat modification. Here we show for the first time, using multiple proxies for vegetation, climate and disturbances from high-resolution, well-dated lake sediments from Lonar Crater in peninsular India, that neither anthropogenic impact nor fire regime shifts, but monsoon weakening during the past ~ 6.0 kyr cal. BP, drove the expansion of savanna at the expense of forests in peninsular India. Our results provide unambiguous evidence for a climate-induced origin and spread of the modern savannas of peninsular India at around the mid-Holocene. We further propose that this savannization preceded and drove the introduction of agriculture and development of sedentism in this region, rather than vice-versa as has often been assumed.
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    Articulating the effect of food systems innovation on the Sustainable Development Goals
    (Amsterdam : Elsevier, 2021) Herrero, Mario; Thornton, Philip K.; Mason-D'Croz, Daniel; Palmer, Jeda; Bodirsky, Benjamin L.; Pradhan, Prajal; Barrett, Christopher B.; Benton, Tim G.; Hall, Andrew; Pikaar, Ilje; Bogard, Jessica R.; Bonnett, Graham D.; Bryan, Brett A.; Campbell, Bruce M.; Christensen, Svend; Clark, Michael; Fanzo, Jessica; Godde, Cecile M.; Jarvis, Andy; Loboguerrero, Ana Maria; Mathys, Alexander; McIntyre, C. Lynne; Naylor, Rosamond L.; Nelson, Rebecca; Obersteiner, Michael; Parodi, Alejandro; Popp, Alexander; Ricketts, Katie; Smith, Pete; Valin, Hugo; Vermeulen, Sonja J.; Vervoort, Joost; van Wijk, Mark; van Zanten, Hannah HE; West, Paul C.; Wood, Stephen A.; Rockström, Johan
    Food system innovations will be instrumental to achieving multiple Sustainable Development Goals (SDGs). However, major innovation breakthroughs can trigger profound and disruptive changes, leading to simultaneous and interlinked reconfigurations of multiple parts of the global food system. The emergence of new technologies or social solutions, therefore, have very different impact profiles, with favourable consequences for some SDGs and unintended adverse side-effects for others. Stand-alone innovations seldom achieve positive outcomes over multiple sustainability dimensions. Instead, they should be embedded as part of systemic changes that facilitate the implementation of the SDGs. Emerging trade-offs need to be intentionally addressed to achieve true sustainability, particularly those involving social aspects like inequality in its many forms, social justice, and strong institutions, which remain challenging. Trade-offs with undesirable consequences are manageable through the development of well planned transition pathways, careful monitoring of key indicators, and through the implementation of transparent science targets at the local level.
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    A network-based microfoundation of Granovetter’s threshold model for social tipping
    ([London] : Macmillan Publishers Limited, part of Springer Nature, 2020) Wiedermann, Marc; Smith, E. Keith; Heitzig, Jobst; Donges, Jonathan F.
    Social tipping, where minorities trigger larger populations to engage in collective action, has been suggested as one key aspect in addressing contemporary global challenges. Here, we refine Granovetter’s widely acknowledged theoretical threshold model of collective behavior as a numerical modelling tool for understanding social tipping processes and resolve issues that so far have hindered such applications. Based on real-world observations and social movement theory, we group the population into certain or potential actors, such that – in contrast to its original formulation – the model predicts non-trivial final shares of acting individuals. Then, we use a network cascade model to explain and analytically derive that previously hypothesized broad threshold distributions emerge if individuals become active via social interaction. Thus, through intuitive parameters and low dimensionality our refined model is adaptable to explain the likelihood of engaging in collective behavior where social-tipping-like processes emerge as saddle-node bifurcations and hysteresis. © 2020, The Author(s).
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    Ambient carbon monoxide and daily mortality: a global time-series study in 337 cities
    (Amsterdam : Elsevier, 2021) Chen, Kai; Breitner, Susanne; Wolf, Kathrin; Stafoggia, Massimo; Sera, Francesco; Vicedo-Cabrera, Ana M.; Guo, Yuming; Tong, Shilu; Lavigne, Eric; Matus, Patricia; Valdés, Nicolás; Kan, Haidong; Jaakkola, Jouni J. K.; Ryti, Niilo R. I.; Huber, Veronika; Scortichini, Matteo; Hashizume, Masahiro; Honda, Yasushi; Nunes, Baltazar; Madureira, Joana; Holobâcă, Iulian Horia; Fratianni, Simona; Kim, Ho; Lee, Whanhee; Tobias, Aurelio; Íñiguez, Carmen; Forsberg, Bertil; Åström, Christofer; Ragettli, Martina S.; Guo, Yue-Liang Leon; Chen, Bing-Yu; Li, Shanshan; Milojevic, Ai; Zanobetti, Antonella; Schwartz, Joel; Bell, Michelle L.; Gasparrini, Antonio; Schneider, Alexandra
    Background Epidemiological evidence on short-term association between ambient carbon monoxide (CO) and mortality is inconclusive and limited to single cities, regions, or countries. Generalisation of results from previous studies is hindered by potential publication bias and different modelling approaches. We therefore assessed the association between short-term exposure to ambient CO and daily mortality in a multicity, multicountry setting. Methods We collected daily data on air pollution, meteorology, and total mortality from 337 cities in 18 countries or regions, covering various periods from 1979 to 2016. All included cities had at least 2 years of both CO and mortality data. We estimated city-specific associations using confounder-adjusted generalised additive models with a quasi-Poisson distribution, and then pooled the estimates, accounting for their statistical uncertainty, using a random-effects multilevel meta-analytical model. We also assessed the overall shape of the exposure–response curve and evaluated the possibility of a threshold below which health is not affected. Findings Overall, a 1 mg/m3 increase in the average CO concentration of the previous day was associated with a 0·91% (95% CI 0·32–1·50) increase in daily total mortality. The pooled exposure–response curve showed a continuously elevated mortality risk with increasing CO concentrations, suggesting no threshold. The exposure–response curve was steeper at daily CO levels lower than 1 mg/m3, indicating greater risk of mortality per increment in CO exposure, and persisted at daily concentrations as low as 0·6 mg/m3 or less. The association remained similar after adjustment for ozone but was attenuated after adjustment for particulate matter or sulphur dioxide, or even reduced to null after adjustment for nitrogen dioxide. Interpretation This international study is by far the largest epidemiological investigation on short-term CO-related mortality. We found significant associations between ambient CO and daily mortality, even at levels well below current air quality guidelines. Further studies are warranted to disentangle its independent effect from other traffic-related pollutants.
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    Decay radius of climate decision for solar panels in the city of Fresno, USA
    ([London] : Macmillan Publishers Limited, part of Springer Nature, 2021) Barton-Henry, Kelsey; Wenz, Leonie; Levermann, Anders
    To design incentives towards achieving climate mitigation targets, it is important to understand the mechanisms that affect individual climate decisions such as solar panel installation. It has been shown that peer effects are important in determining the uptake and spread of household photovoltaic installations. Due to coarse geographical data, it remains unclear whether this effect is generated through geographical proximity or within groups exhibiting similar characteristics. Here we show that geographical proximity is the most important predictor of solar panel implementation, and that peer effects diminish with distance. Using satellite imagery, we build a unique geo-located dataset for the city of Fresno to specify the importance of small distances. Employing machine learning techniques, we find the density of solar panels within the shortest measured radius of an address is the most important factor in determining the likelihood of that address having a solar panel. The importance of geographical proximity decreases with distance following an exponential curve with a decay radius of 210 meters. The dependence is slightly more pronounced in low-income groups. These findings support the model of distance-related social diffusion, and suggest priority should be given to seeding panels in areas where few exist.
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    Short term associations of ambient nitrogen dioxide with daily total, cardiovascular, and respiratory mortality: multilocation analysis in 398 cities
    (London : BMJ Publ. Group, 2021) Meng, Xia; Liu, Cong; Chen, Renjie; Sera, Francesco; Vicedo-Cabrera, Ana Maria; Milojevic, Ai; Guo, Yuming; Tong, Shilu; Coelho, Micheline de Sousa Zanotti Stagliorio; Saldiva, Paulo Hilario Nascimento; Lavigne, Eric; Correa, Patricia Matus; Ortega, Nicolas Valdes; Osorio, Samuel; Garcia, null; Kyselý, Jan; Urban, Aleš; Orru, Hans; Maasikmets, Marek; Jaakkola, Jouni J. K.; Ryti, Niilo; Huber, Veronika; Schneider, Alexandra; Katsouyanni, Klea; Analitis, Antonis; Hashizume, Masahiro; Honda, Yasushi; Ng, Chris Fook Sheng; Nunes, Baltazar; Teixeira, João Paulo; Holobaca, Iulian Horia; Fratianni, Simona; Kim, Ho; Tobias, Aurelio; Íñiguez, Carmen; Forsberg, Bertil; Åström, Christofer; Ragettli, Martina S.; Guo, Yue-Liang Leon; Pan, Shih-Chun; Li, Shanshan; Bell, Michelle L.; Zanobetti, Antonella; Schwartz, Joel; Wu, Tangchun; Gasparrini, Antonio; Kan, Haidong
    Objective To evaluate the short term associations between nitrogen dioxide (NO2) and total, cardiovascular, and respiratory mortality across multiple countries/regions worldwide, using a uniform analytical protocol. Design Two stage, time series approach, with overdispersed generalised linear models and multilevel meta-analysis. Setting 398 cities in 22 low to high income countries/regions. Main outcome measures Daily deaths from total (62.8 million), cardiovascular (19.7 million), and respiratory (5.5 million) causes between 1973 and 2018. Results On average, a 10 μg/m3 increase in NO2 concentration on lag 1 day (previous day) was associated with 0.46% (95% confidence interval 0.36% to 0.57%), 0.37% (0.22% to 0.51%), and 0.47% (0.21% to 0.72%) increases in total, cardiovascular, and respiratory mortality, respectively. These associations remained robust after adjusting for co-pollutants (particulate matter with aerodynamic diameter ≤10 μm or ≤2.5 μm (PM10 and PM2.5, respectively), ozone, sulfur dioxide, and carbon monoxide). The pooled concentration-response curves for all three causes were almost linear without discernible thresholds. The proportion of deaths attributable to NO2 concentration above the counterfactual zero level was 1.23% (95% confidence interval 0.96% to 1.51%) across the 398 cities. Conclusions This multilocation study provides key evidence on the independent and linear associations between short term exposure to NO2 and increased risk of total, cardiovascular, and respiratory mortality, suggesting that health benefits would be achieved by tightening the guidelines and regulatory limits of NO2.
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    Anti-correlation of HER2 and focal adhesion complexes in the plasma membrane
    (San Francisco : Public Library of Science, 2020) Weinberg, F.; Han, M.K.L.; Dahmke, I.N.; Campo, A.D.; de Jonge, N.
    Excess presence of the human epidermal growth factor receptor 2 (HER2) as well as of the focal adhesion protein complexes are associated with increased proliferation, migratory, and invasive behavior of cancer cells. A cross-regulation between HER2 and integrin signaling pathways has been found, but the exact mechanism remains elusive. Here, we investigated whether HER2 colocalizes with focal adhesion complexes on breast cancer cells overexpressing HER2. For this purpose, vinculin or talin green fluorescent protein (GFP) fusion proteins, both key constituents of focal adhesions, were expressed in breast cancer cells. HER2 was either extracellularly or intracellularly labeled with fluorescent quantum dots nanoparticles (QDs). The cell-substrate interface was analyzed at the location of the focal adhesions by means of total internal reflection fluorescent microscopy or correlative fluorescence- and scanning transmission electron microscopy. Expression of HER2 at the cell-substrate interface was only observed upon intracellular labeling, and was heterogeneous with both HER2-enriched and -low regions. In contrast to an expected enrichment of HER2 at focal adhesions, an anti-correlated expression pattern was observed for talin and HER2. Our findings suggest a spatial anti-correlation between HER2 and focal adhesion complexes for adherent cells.