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Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection

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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Computational design and optimization of electro-physiological sensors

2021, Nittala, Aditya Shekhar, Karrenbauer, Andreas, Khan, Arshad, Kraus, Tobias, Steimle, JĂĽrgen

Electro-physiological sensing devices are becoming increasingly common in diverse applications. However, designing such sensors in compact form factors and for high-quality signal acquisition is a challenging task even for experts, is typically done using heuristics, and requires extensive training. Our work proposes a computational approach for designing multi-modal electro-physiological sensors. By employing an optimization-based approach alongside an integrated predictive model for multiple modalities, compact sensors can be created which offer an optimal trade-off between high signal quality and small device size. The task is assisted by a graphical tool that allows to easily specify design preferences and to visually analyze the generated designs in real-time, enabling designer-in-the-loop optimization. Experimental results show high quantitative agreement between the prediction of the optimizer and experimentally collected physiological data. They demonstrate that generated designs can achieve an optimal balance between the size of the sensor and its signal acquisition capability, outperforming expert generated solutions.

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The 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

2021, Scholz, Juliane, Wetzker, Wibke, Licht, Annika, Heintzmann, Rainer, Scherag, André, Weis, Sebastian, Pletz, Mathias, Betsch, Cornelia, Bauer, Michael, Dickmann, Petra, Frey, Rosemary

Background: 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.

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Climate change and specialty coffee potential in Ethiopia

2021, Chemura, Abel, Mudereri, Bester Tawona, Yalew, Amsalu Woldie, Gornott, Christoph

Current climate change impact studies on coffee have not considered impact on coffee typicities that depend on local microclimatic, topographic and soil characteristics. Thus, this study aims to provide a quantitative risk assessment of the impact of climate change on suitability of five premium specialty coffees in Ethiopia. We implement an ensemble model of three machine learning algorithms to predict current and future (2030s, 2050s, 2070s, and 2090s) suitability for each specialty coffee under four Shared Socio-economic Pathways (SSPs). Results show that the importance of variables determining coffee suitability in the combined model is different from those for specialty coffees despite the climatic factors remaining more important in determining suitability than topographic and soil variables. Our model predicts that 27% of the country is generally suitable for coffee, and of this area, only up to 30% is suitable for specialty coffees. The impact modelling showed that the combined model projects a net gain in coffee production suitability under climate change in general but losses in five out of the six modelled specialty coffee growing areas. We conclude that depending on drivers of suitability and projected impacts, climate change will significantly affect the Ethiopian speciality coffee sector and area-specific adaptation measures are required to build resilience.

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Reply to Bhowmik et al.: Democratic climate action and studying extreme climate risks are not in tension

2022, Kemp, Luke, Xu, Chi, Depledge, Joanna, Ebi, Kristie L., Gibbins, Goodwin, Kohler, Timothy A., Rockström, Johan, Scheffer, Marten, Schellnhuber, Hans Joachim, Steffen, Will, Lenton, Timothy M.

[no abstract available]

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We need biosphere stewardship that protects carbon sinks and builds resilience

2021, Rockström, Johan, Beringer, Tim, Hole, David, Griscom, Bronson, Mascia, Michael B., Folke, Carl, Creutzig, Felix

[no abstract available]

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Reply to Burgess et al: Catastrophic climate risks are neglected, plausible, and safe to study

2022, Kemp, Luke, Xu, Chi, Depledge, Joanna, Ebi, Kristie L., Gibbins, Goodwin, Kohler, Timothy A., Rockström, Johan, Scheffer, Marten, Schellnhuber, Hans Joachim, Steffen, Will, Lenton, Timothy M.

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Research data management in agricultural sciences in Germany: We are not yet where we want to be

2022, Senft, Matthias, Stahl, Ulrike, Svoboda, Nikolai

To 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.

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Scanning electron microscopy preparation of the cellular actin cortex: A quantitative comparison between critical point drying and hexamethyldisilazane drying

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.

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Intestinal epithelial barrier integrity investigated by label-free techniques in ulcerative colitis patients

2023, Quansah, Elsie, Gardey, Elena, Ramoji, Anuradha, Meyer-Zedler, Tobias, Goehrig, Bianca, Heutelbeck, Astrid, Hoeppener, Stephanie, Schmitt, Michael, Waldner, Maximillian, Stallmach, Andreas, Popp, JĂĽrgen

The intestinal epithelial barrier, among other compartments such as the mucosal immune system, contributes to the maintenance of intestinal homeostasis. Therefore, any disturbance within the epithelial layer could lead to intestinal permeability and promote mucosal inflammation. Considering that disintegration of the intestinal epithelial barrier is a key element in the etiology of ulcerative colitis, further assessment of barrier integrity could contribute to a better understanding of the role of epithelial barrier defects in ulcerative colitis (UC), one major form of chronic inflammatory bowel disease. Herein, we employ fast, non-destructive, and label-free non-linear methods, namely coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG), two-photon excited fluorescence (TPEF), and two-photon fluorescence lifetime imaging (2P-FLIM), to assess the morpho-chemical contributions leading to the dysfunction of the epithelial barrier. For the first time, the formation of epithelial barrier gaps was directly visualized, without sophisticated data analysis procedures, by the 3D analysis of the colonic mucosa from severely inflamed UC patients. The results were compared with histopathological and immunofluorescence images and validated using transmission electron microscopy (TEM) to indicate structural alterations of the apical junction complex as the underlying cause for the formation of the epithelial barrier gaps. Our findings suggest the potential advantage of non-linear multimodal imaging is to give precise, detailed, and direct visualization of the epithelial barrier in the gastrointestinal tract, which can be combined with a fiber probe for future endomicroscopy measurements during real-time in vivo imaging.