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- ItemNon-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, FatahEffective 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.
- ItemPDA 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, HugoCastrate 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.
- ItemAccurate 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, TuanFor 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.
- ItemArticulating 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, JohanFood 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.
- ItemDynamic fine-tuning of CAR-T cell therapy(London : Nature Publishing Group, 2023) Trehin, Pierre V.M.; Muñoz-Guamuro, Geisler; Weber, Wilfried[No abstract available]
- ItemAmbient 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, AlexandraBackground 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.
- ItemShort 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, HaidongObjective 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.
- ItemResearch data management in agricultural sciences in Germany: We are not yet where we want to be(San Francisco, California, US : PLOS, 2022) Senft, Matthias; Stahl, Ulrike; Svoboda, NikolaiTo meet the future challenges and foster integrated and holistic research approaches in agricultural sciences, new and sustainable methods in research data management (RDM) are needed. The involvement of scientific users is a critical success factor for their development. We conducted an online survey in 2020 among different user groups in agricultural sciences about their RDM practices and needs. In total, the questionnaire contained 52 questions on information about produced and (re-)used data, data quality aspects, information about the use of standards, publication practices and legal aspects of agricultural research data, the current situation in RDM in regards to awareness, consulting and curricula as well as needs of the agricultural community in respect to future developments. We received 196 (partially) completed questionnaires from data providers, data users, infrastructure and information service providers. In addition to the diversity in the research data landscape of agricultural sciences in Germany, the study reveals challenges, deficits and uncertainties in handling research data in agricultural sciences standing in the way of access and efficient reuse of valuable research data. However, the study also suggests and discusses potential solutions to enhance data publications, facilitate and secure data re-use, ensure data quality and develop services (i.e. training, support and bundling services). Therefore, our research article provides the basis for the development of common RDM, future infrastructures and services needed to foster the cultural change in handling research data across agricultural sciences in Germany and beyond.
- ItemScanning electron microscopy preparation of the cellular actin cortex: A quantitative comparison between critical point drying and hexamethyldisilazane drying(San Francisco, California, US : PLOS, 2021) Schu, Moritz; Terriac, Emmanuel; Koch, Marcus; Paschke, Stephan; Lautenschläger, Franziska; Flormann, Daniel A.D.The cellular cortex is an approximately 200-nm-thick actin network that lies just beneath the cell membrane. It is responsible for the mechanical properties of cells, and as such, it is involved in many cellular processes, including cell migration and cellular interactions with the environment. To develop a clear view of this dense structure, high-resolution imaging is essential. As one such technique, electron microscopy, involves complex sample preparation procedures. The final drying of these samples has significant influence on potential artifacts, like cell shrinkage and the formation of artifactual holes in the actin cortex. In this study, we compared the three most used final sample drying procedures: critical-point drying (CPD), CPD with lens tissue (CPD-LT), and hexamethyldisilazane drying. We show that both hexamethyldisilazane and CPD-LT lead to fewer artifactual mesh holes within the actin cortex than CPD. Moreover, CPD-LT leads to significant reduction in cell height compared to hexamethyldisilazane and CPD. We conclude that the final drying procedure should be chosen according to the reduction in cell height, and so CPD-LT, or according to the spatial separation of the single layers of the actin cortex, and so hexamethyldisilazane.
- ItemThe role of risk communication in public health interventions. An analysis of risk communication for a community quarantine in Germany to curb the SARS-CoV-2 pandemic(San Francisco, California, US : PLOS, 2021) Scholz, Juliane; Wetzker, Wibke; Licht, Annika; Heintzmann, Rainer; Scherag, André; Weis, Sebastian; Pletz, Mathias; Betsch, Cornelia; Bauer, Michael; Dickmann, Petra; Frey, RosemaryBackground: Separating ill or possibly infectious people from their healthy community is one of the core principles of non-pharmaceutical interventions. However, there is scarce evidence on how to successfully implement quarantine orders. We investigated a community quarantine for an entire village in Germany (Neustadt am Rennsteig, March 2020) with the aim of better understanding the successful implementation of quarantine measures. Methods: This cross-sectional survey was conducted in Neustadt am Rennsteig six weeks after the end of a 14-day mandatory community quarantine. The sample size consisted of 562 adults (64% of the community), and the response rate was 295 adults, or 52% (33% of the community). Findings: National television was reported as the most important channel of information. Contact with local authorities was very limited, and partners or spouses played a more important role in sharing information. Generally, the self-reported information level was judged to be good (211/289 [73.0%]). The majority of participants (212/289 [73.4%]) approved of the quarantine, and the reported compliance was 217/289 (75.1%). A self-reported higher level of concern as well as a higher level of information correlated positively with both a greater acceptance of quarantine and self-reported compliant behaviour. Interpretation: The community quarantine presented a rare opportunity to investigate a public health intervention for an entire community. In order to improve the implementation of public health interventions, public health risk communication activities should be intensified to increase both the information level (potentially leading to better compliance with community quarantine) and the communication level (to facilitate rapport and trust between public health authorities and their communities). © 2021 Scholz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.