Dielectric Properties of Materials Used for Microwave-Based NOx Gas Dosimeters.

Nitrogen oxides (NOx), primarily generated from combustion processes, pose significant health and environmental risks. To improve the coordination of measures against excessive NOx emissions, it is necessary to effectively monitor ambient NOx concentrations, which requires the development of precise and cost-efficient detection methods. This study focuses on developing a microwave- or radio frequency (RF)-based gas dosimeter for NOx detection and addresses the optimization of the dosimeter design by examining the dielectric properties of LTCC-based (Low-Temperature Co-fired Ceramics) sensor substrates and barium-based NOx storage materials. The measurements taken utilizing the Microwave Cavity Perturbation (MCP) method revealed that these materials exhibit more pronounced changes in dielectric losses when storing NOx at elevated temperatures. Consequently, operating such a dosimeter at high temperatures (above 300 °C) is recommended to maximize the sensor signal. To evaluate their high-temperature applicability, LTCC substrates were analyzed by measuring their dielectric losses at temperatures up to 600 °C. In terms of NOx storage materials, coating barium on high-surface-area alumina resolved issues related to limited NOx adsorption in pure barium carbonate powders. Additionally, the adsorption of both NO and NO2 was enabled by the application of a platinum catalyst. The change in dielectric losses, which provides the main signal for an RF-based gas dosimeter, only depends on the stored amount of NOx and not on the specific type of nitrogen oxide. Although the change in dielectric losses increases with the temperature, the maximum storage capacity of the material decreases significantly. In addition, at temperatures above 350 °C, NOx is mostly weakly bound, so it will desorb in the absence of NOx. Therefore, in the future development of a reliable RF-based NOx dosimeter, the trade-off between the sensor signal strength and adsorption behavior must be addressed.

ROCK1/2 signaling contributes to corticosteroid-refractory acute graft-versus-host disease.

Patients with corticosteroid-refractory acute graft-versus-host disease (aGVHD) have a low one-year survival rate. Identification and validation of novel targetable kinases in patients who experience corticosteroid-refractory-aGVHD may help improve outcomes. Kinase-specific proteomics of leukocytes from patients with corticosteroid-refractory-GVHD identified rho kinase type 1 (ROCK1) as the most significantly upregulated kinase. ROCK1/2 inhibition improved survival and histological GVHD severity in mice and was synergistic with JAK1/2 inhibition, without compromising graft-versus-leukemia-effects. ROCK1/2-inhibition in macrophages or dendritic cells prior to transfer reduced GVHD severity. Mechanistically, ROCK1/2 inhibition or ROCK1 knockdown interfered with CD80, CD86, MHC-II expression and IL-6, IL-1ß, iNOS and TNF production in myeloid cells. This was accompanied by impaired T cell activation by dendritic cells and inhibition of cytoskeletal rearrangements, thereby reducing macrophage and DC migration. NF-κB signaling was reduced in myeloid cells following ROCK1/2 inhibition. In conclusion, ROCK1/2 inhibition interferes with immune activation at multiple levels and reduces acute GVHD while maintaining GVL-effects, including in corticosteroid-refractory settings.

Soot Monitoring of Gasoline Particulate Filters Using a Radio-Frequency-Based Sensor.

Owing to increasingly stringent emission limits, particulate filters have become mandatory for gasoline-engine vehicles. Monitoring their soot loading is necessary for error-free operation. The state-of-the-art differential pressure sensors suffer from inaccuracies due to small amounts of stored soot combined with exhaust gas conditions that lead to partial regeneration. As an alternative approach, radio-frequency-based (RF) sensors can accurately measure the soot loading, even under these conditions, by detecting soot through its dielectric properties. However, they face a different challenge as their sensitivity may depend on the engine operation conditions during soot formation. In this article, this influence is evaluated in more detail. Various soot samples were generated on an engine test bench. Their dielectric properties were measured using the microwave cavity perturbation (MCP) method and compared with the corresponding sensitivity of the RF sensor determined on a lab test bench. Both showed similar behavior. The values for the soot samples themselves, however, differed significantly from each other. A way to correct for this cross-sensitivity was found in the influence of exhaust gas humidity on the RF sensor, which can be correlated with the engine load. By evaluating this influence during significant humidity changes, such as fuel cuts, it could be used to correct the influence of the engineon the RF sensor.

Malnutrition in Head and Neck Cancer: A Patient-reported Outcome Study.

BACKGROUND/AIM: Head and neck cancer (HNC) is associated with a high risk of malnutrition. Malnutrition is defined as acute weight loss greater than 5% and increases mortality 1.7-fold for HNC patients. The aim of the study was to investigate the social and nutritional impairments that patients face throughout cancer-survivorship. PATIENTS AND METHODS: The study was conducted nationwide via the self-help network and in a single oncological center. We analysed 134 patient reported outcome (PRO) questionnaires with a mean age of 65.5±9.4 years, including 88 males, 36 females, and ten participants of undisclosed sex. The questionnaire contained 47 items enquiring about demography, weight development, and how treatment impaired nutrition. RESULTS: The patient data showed a weight loss of 8% after surgery, 13% after (chemo)radiotherapy [(C)RT] and a return to baseline weight in convalescence. However, patients with a baseline weight >100 kilogram (kg), had a 22% weight loss after (C)RT (p<0.0001) and this remained permanent at 11% (p=0.0041). Treatment-associated side-effects gradually decreased in the course compared to the time of treatment: loss of taste (55% to 21%), xerostomia (56% to 42%), dysphagia (57% to 43%), and dental problems (33%/ to 21%). (C)RT immediately led to more loss of taste (p=0.0461) and dysphagia (p=0.0334), and surgery as a singular modality scored the lowest odds ratio for side-effects. Social Impact: mood, supporting networks, and supplement satisfaction were rated "good" (Likert Scale). CONCLUSION: Malnutrition is common among HNC patients. High baseline weight and extensive multimodal treatment are important risk factors that require enhanced stewardship.

High phosphate-induced progressive proximal tubular injury is associated with the activation of Stat3/Kim-1 signaling pathway and macrophage recruitment.

Dietary phosphate intake in the Western population greatly exceeds the recommended dietary allowance and is linked to enhanced cardiovascular and all-cause mortality. It is unclear whether a chronic high phosphate diet (HPD) causes kidney injury in healthy individuals. Here, we show that feeding a 2% HPD in C57BL/6N mice for one up to six months resulted in hyperphosphatemia, hyperphosphaturia, increased plasma levels of fibroblast growth factor (FGF) 23, and parathyroid hormone (PTH) compared to mice on a 0.8% phosphate diet. Kidney injury was already noted after two months of HPD characterized by loss of proximal tubular (PT) cell polarity, flattened epithelia, disruption of brush border membranes, vacuolization, increased PT cell proliferation, marked interstitial mononuclear infiltration, and progressive accumulation of collagen fibers. HPD increased Stat3 activation and Kim-1 expression in PT epithelial cells and enhanced renal synthesis of chemokines recruiting monocytes and macrophages as well as macrophage related factors. Enhanced recruitment of F4/80+ macrophages around injured PT lesions was timely associated with increased Kim-1 synthesis, tubular MCP-1 expression, and degree of PT injury score. Likewise, tubulointerstitial fibrosis was associated with activation of Stat3/Kim-1 signaling pathway. The stimulation of human proximal tubular cells with high phosphate activated Stat3 signaling and induced HAVCR1 and CCL2 expression. We conclude that high phosphate results in progressive proximal tubular injury, indicating that high dietary phosphate intake may affect kidney health and therefore represents an underestimated health problem for the general population.

Mixing Rules for an Exact Determination of the Dielectric Properties of Engine Soot Using the Microwave Cavity Perturbation Method and Its Application in Gasoline Particulate Filters.

In recent years, particulate filters have become mandatory in almost all gasoline-powered vehicles to comply with emission standards regarding particulate number. In contrast to diesel applications, monitoring gasoline particulate filters (GPFs) by differential pressure sensors is challenging due to lower soot masses to be deposited in the GPFs. A different approach to determine the soot loading of GPFs is a radio frequency-based sensor (RF sensor). To facilitate sensor development, in previous work, a simulation model was created to determine the RF signal at arbitrary engine operating points. To ensure accuracy, the exact dielectric properties of the soot need to be known. This work has shown how small samples of soot-loaded filter are sufficient to determine the dielectric properties of soot itself using the microwave cavity perturbation method. For this purpose, mixing rules were determined through simulation and measurement, allowing the air and substrate fraction of the sample to be considered. Due to the different geometry of filter substrates compared to crushed soot samples, a different mixing rule had to be derived to calculate the effective filter properties required for the simulation model. The accuracy of the determined mixing rules and the underlying simulation model could be verified by comparative measurements on an engine test bench.

Tumor patients' fears and worries and perceived changes of specific attitudes, perceptions and behaviors due to the COVID-19 pandemic are still relevant.

OBJECTIVE: During the COVID-19 pandemic, tumor patients not only perceived fears and worries but were experiencing also positive changes as the perception of nature and silence, moments of wondering awe, and more intense relationships. We intended to analyze whether these perceptions may differ between patients from waves 1 and 2 of the pandemic. METHODS: Cross-sectional study at two time periods (May to June, sample 1) and September to November 2020 (sample 2) with standardized questionnaires (i.e. WHO-5, MLQ, PCQ-12). RESULTS: Patients from sample 1 (n = 292) and sample 2 (n = 221) did not differ with respect to gender, age, partner or tumor status. Most are still "irritated by statements about danger and course of the infection" (58%) and are "worrying to be infected and to have complicated course of disease" (55%). Neither their well-being nor meaning in life nor fears and worries were significantly different. In sample 2 patients, Worrying reflections and loneliness scored significantly lower, while their Perception of nature and silence was lower in trend only; more intense relationships are still relevant. Moments of wondering awe and religious trust were perceived less often during wave 2. Particularly religious patients scored stronger for Perception of nature and silence and Worrying reflections and loneliness. CONCLUSION: Oncologists/psychologist have to know that patients' situation has not changed within the time of pandemic and that they still require information, close support and encouragement to rely on their resources to cope. Perceived changes are reflecting coping strategies that could be trained to increase patients' resilience during further pandemic waves.

Take care or "German Angst"? Lessons from cancer care during COVID-19 pandemic in spring 2020.

OBJECTIVE: While the second wave of COVID-19 has started in Europe, data are still missing on the consequences of the first one for patients with cancer. The aim of our study was to learn more about the experiences of German patients and staff in the oncology services. MATERIALS AND METHODS: An anonymous online survey was conducted among cancer patients and their therapists (physicians, medical staff, psychologists, spiritual care givers) in Germany between April and May 2020 asking about burden, fears, and perceived changes in German oncology service system. Besides answer frequencies of different stakeholders, uni- and multivariate analyses were performed for selected items to identify areas of high impact. RESULTS: In total 752 participants were included. All groups have identified high mental burden as central problem. A majority was confused about varying information policies and strategies against the pandemic. Patient reported restricted visits, isolation and delay of treatment as central fears and problems. The majority of fears could be coped by the health care workers. The patients describe processes at the oncology services during the first wave. Personal experiences with COVID-19 have had no influence on the felt burden of the patients. Physicians, medical staff, psychologists and spiritual care givers were extremely stressed but repressed their own burden. They await financial, physical and mental problems for their own future. CONCLUSIONS: The presented personal views and experiences allow focusing the discussions about heath care systems during the on-going pandemic. Support for health care workers, as much routine as possible in oncology services, and transparency in information will be the keys for good management in futural situations of crisis.

EU-27 Public Opinion on Brexit.

Although there has been much interest in British public opinion on Brexit, much less is known about how EU-27 Europeans view the Brexit negotiations. This is surprising, because Brexit confronts the EU-27 with difficult choices. Whereas accommodating the UK carries the risk of encouraging further countriesto leave the EU, an uncompromising negotiation stance increases the economic and social costs of Brexit. Using original survey data from 39,000 respondents in all EU-27 countries collected between the start of the Brexit negotiations and December 2018, this article shows that exposure to the economic risks of Brexit makes respondents more willing to accommodate the UK, whereas a positive opinion of the EU decreases their willingness to compromise. Moreover, many Europeans face an accommodation dilemma that moderates these preferences. Overall, the EU-27 public unsentimentally supports a Brexit negotiation line that safeguards their own interests best.

[Oncology Services for Patients with Head Neck Cancer during Corona-Times - Patients' Perspective]. / Auswirkungen der COVID-19-Pandemie auf die Versorgung von HNO-Tumoren ­ die Patientenperspektive.

OBJECTIVE: COVID-19 pandemic has impact on the oncology service system for tumor patients. What is the view of head and neck cancer patients (HNC) on this situation and which coping strategies were developed? MATERIAL & METHODS: In study 1 PRIO asked 433 tumor patients regarding their impressions/fears during the lockdown between April 15 and May 15, 2020 (online, standardized questionnaire). In 2nd study 292 tumor patients reported their pandemic-induced perceived changes and coping strategies by established questionnaires (WHO-5, MLQ, GrAw-7). An analysis of the HNC-data obtained by standardized questionnaires was performed. RESULTS: Study 1 had 91 HNC, study 2-84 HNC. Study 1 shows high stress levels for the majority of HNC (53,8 %). Personal fears regarding the own disease and therapies (39.6 %) are a central problem. The participants await physical (24.7 %) as well as psychological (21.3 %) consequences due to the pandemic and its current management. During the lockdown the isolation (banned visitors at any hospital) was discussed as critical main point by 58.5 % of HNC patients. Study 2 (after lockdown) underlined the mental stress caused by pandemic. Intensified relations within the families (58/100 points) as well as more intensive experience of nature and silence (58/60 points) are the most perceived changes in corona-times. HNC showed increased own inactivity (MLQ) and depressed well-being (WHO-5) and attention to the moment (GrAw-7). CONCLUSIONS: HNC patients have had high burden and fears due to the COVID-19 pandemic in spring 2020. Their views are important for further strategies to organize and stabilize the oncology service system during further pandemic periods.

Assessment of Self-Efficacy as a Way to Help Identify Cancer Patients Who Might Benefit from Self-Help Group Attendance?

Participating in patient self-help groups is highly recommended to patients in cancer care. Yet, engagement is relatively rare. A total of 253 patients participated in our study conducted as a paper-and-pencil questionnaire. A binominal logistic regression, with interest in participation in self-help groups being the dependent variable, was run. General interest in self-help was high among the respondents. Female gender, higher age, higher education and low self-efficacy were found to significantly predict interest in self-help. Patients reported a lack of information provided by medical professionals. Self-efficacy as a predictor might contribute to characterizing patients who might benefit from self-help group participation.

Tumor Patients´ Perceived Changes of Specific Attitudes, Perceptions, and Behaviors Due to the COVID-19 Pandemic and Its Relation to Reduced Wellbeing.

BACKGROUND: During the COVID-19 pandemic, the Working Group "Prevention and Integrative Oncology" (PRIO) in the German Cancer Society has initiated flash interviews and surveys. One of these stated increasing rates of fears and mental stress of tumor patients. Now we aimed to analyze whether tumor patients did perceive changes in their attitudes and behaviors related to their relationships, awareness of nature and quietness, interest in spiritual issues, or feelings of worries and isolation. A further point of interest was how these perceived changes could be predicted, either by meaning in life, spirituality as a resource to cope, perceived fears and worries, or particularly by their wellbeing. MATERIALS AND METHODS: Online survey with standardized questionnaires (i.e., WHO-Five Well-being Index (WHO5), Meaning in Life Questionnaire (MLQ), Spiritual and Religious Attitudes to cope with illness (SpREUK-15), Gratitude/Awe scale (GrAw-7)) among 292 tumor patients (72% men; mean age 66.7 ± 10.8 years; 25% < 60 years, 33% 60-70 years, 41% > 70 years) from Germany between May 6 to June 10, 2020. RESULTS: Patients´ wellbeing (WHO5) scores were in the lower range (14.7 ± 6.0); 35% scored < 13, indicating depressive states. Wellbeing was significantly higher in older persons and lower in younger ones (F=11.1, p<.0001). Most were irritated by different statements about the danger and the course of the corona infection in the public media (60%), and 57% were worrying to be infected and to have a complicated course of disease. Because of the restrictions, patients noticed changes in their attitudes and behaviors (measured with the 12-item Perceptions of Change Scale): 1) Perception of nature and silence (Cronbach´s alpha = .82), 2) Worrying reflections and loneliness (Cronbach´s alpha = .80), 3) Interest in spirituality (Cronbach´s alpha = .91), 4) Intense relationships (Cronbach´s alpha = .64). These perceptions of change were similar in women and men, age groups and also with respect to tumor stages. Regression analyses revealed that the factor Perception of nature and silence was predicted best by patients´ ability to value and experience the 'wonder' of the present moment (in terms of wondering awe and gratitude) and by patients´ search for meaning in life. The factor Worrying reflections and loneliness was predicted best by their search for meaning in life and by feelings of being under pressure because of the Corona pandemic. Interest in spirituality was predicted best by search for an access to a spiritual source and by frequency of praying. Intense relationships were explained with weak predictive power by patients´ ability to reflect life concerns. Patients´ wellbeing during the Corona pandemic was predicted (R2 =.57) by a mix of disease and pandemic related stressor, and by available resources (meaning in life and religious trust). CONCLUSION: In this study among tumor patients from a secular society the topics meaning in life, having (religious) trust, stable relationships, mindful encounter with nature, and times of reflection were found to be of importance. To overcome tumor patients´ feelings of isolation, depressive states, and insecurity about future perspectives, further support is needed, particularly in their socio-spatial surrounding. These are the domains of psychotherapy and spiritual care. The planned integration of structured access to spiritual care seems to be important, not only for the field of cancer care. As the findings refer to patients´ self-perceptions, longitudinal studies are required to substantiate these perceived changes.

Determination of the Dielectric Properties of Storage Materials for Exhaust Gas Aftertreatment Using the Microwave Cavity Perturbation Method.

Recently, a laboratory setup for microwave-based characterization of powder samples at elevated temperatures and different gas atmospheres was presented. The setup is particularly interesting for operando investigations on typical materials for exhaust gas aftertreatment. By using the microwave cavity perturbation method, where the powder is placed inside a cavity resonator, the change of the resonant properties provides information about changes in the dielectric properties of the sample. However, determining the exact complex permittivity of the powder samples is not simple. Up to now, a simplified microwave cavity perturbation theory had been applied to estimate the bulk properties of the powders. In this study, an extended approach is presented which allows to determine the dielectric properties of the powder materials more correctly. It accounts for the electric field distribution in the resonator, the depolarization of the sample and the effect of the powder filling. The individual method combines findings from simulations and recognized analytical approaches and can be used for investigations on a wide range of materials and sample geometries. This work provides a more accurate evaluation of the dielectric powder properties and has the potential to enhance the understanding of the microwave behavior of storage materials for exhaust gas aftertreatment, especially with regard to the application of microwave-based catalyst state diagnosis.

Modelling the Influence of Different Soot Types on the Radio-Frequency-Based Load Detection of Gasoline Particulate Filters.

Gasoline particulate filters (GPFs) are an appropriate means to meet today's emission standards. As for diesel applications, GPFs can be monitored via differential pressure sensors or using a radio-frequency approach (RF sensor). Due to largely differing soot properties and engine operating modes of gasoline compared to diesel engines (e.g., the possibility of incomplete regenerations), the behavior of both sensor systems must be investigated in detail. For this purpose, extensive measurements on engine test benches are usually required. To simplify the sensor development, a simulation model was developed using COMSOL Multiphysics® that not only allowed for calculating the loading and regeneration process of GPFs under different engine operating conditions but also determined the impact on both sensor systems. To simulate the regeneration behavior of gasoline soot accurately, an oxidation model was developed. To identify the influence of different engine operating points on the sensor behavior, various samples generated at an engine test bench were examined regarding their kinetic parameters using thermogravimetric analysis. Thus, this compared the accuracy of soot mass determination using the RF sensor with the differential pressure method. By simulating a typical driving condition with incomplete regenerations, the effects of the soot kinetics on sensor accuracy was demonstrated exemplarily. Thereby, the RF sensor showed an overall smaller mass determination error, as well as a lower dependence on the soot kinetics.

Oncology services in corona times: a flash interview among German cancer patients and their physicians.

OBJECTIVE: Public discussion and health-care systems worldwide have been focusing on the COVID-19 pandemic. Does it have an impact on cancer care today? MATERIALS AND METHODS: The PRIO ("Prevention and Integrative Oncology") Working Group (German Cancer Society) has initiated an online survey for physicians, medical staff and patients on April 16, 2020. Between April 16 and April 19, 47 doctors and 146 patients filled in the questionnaires. The survey is ongoing. We present the first data. RESULTS: A majority of German patients (76%) and physicians (71%) report moderate or high restriction in their daily life. A minority (patients 25%, physicians 13%) was not worried that necessary treatments or diagnostics were restricted. Organizing cancer care needs more time and efforts for 56% of all reporting doctors. 98% of all oncologists think that restriction of family visits has a negative impact on the mental health of cancer patients. Half of all participants (patients 43%, physicians 47%) expect negative consequences on the physical status of our patients. Patients feel the existing emotional stress in 34% of their physicians. 52% of physicians fear mental and/or physical longtime consequences for themselves. CONCLUSION: There is a high level of mental and physical stress triggered by the present COVID-19 management. After only a few weeks, human resources are limited. They will be the most important key for further health-care services for patients with cancer and other chronic diseases.

Scientific networks on Twitter: Analyzing scientists' interactions in the climate change debate.

Scientific issues requiring urgent societal actions-such as climate change-have increased the need for communication and interaction between scientists and other societal actors. Social media platforms facilitate such exchanges. This study investigates who scientists interact with on Twitter, and whether their communication differs when engaging with actors beyond the scientific community. We focus on the climate change debate on Twitter and combine network analysis with automated content analysis. The results show that scientists interact most intensively with their peers, but also communication beyond the scientific community is important. The findings suggest that scientists adjust their communication style to their audience: They use more neutral language when communicating with other scientists, and more words expressing negative emotions when communicating with journalists, civil society, and politicians. Likewise, they stress certainty more when communicating with politicians, indicating that scientists use language strategically when communicating beyond the scientific community.

Exclusion from spheroid formation identifies loss of essential cell-cell adhesion molecules in colon cancer cells.

Many cell lines derived from solid cancers can form spheroids, which recapitulate tumor cell clusters and are more representative of the in vivo situation than 2D cultures. During spheroid formation, a small proportion of a variety of different colon cancer cell lines did not integrate into the sphere and lost cell-cell adhesion properties. An enrichment protocol was developed to augment the proportion of these cells to 100% purity. The basis for the separation of spheroids from non-spheroid forming (NSF) cells is simple gravity-sedimentation. This protocol gives rise to sub-populations of colon cancer cells with stable loss of cell-cell adhesion. SW620 cells lacked E-cadherin, DLD-1 cells lost α-catenin and HCT116 cells lacked P-cadherin in the NSF state. Knockdown of these molecules in the corresponding spheroid-forming cells demonstrated that loss of the respective proteins were indeed responsible for the NSF phenotypes. Loss of the spheroid forming phenotype was associated with increased migration and invasion properties in all cell lines tested. Hence, we identified critical molecules involved in spheroid formation in different cancer cell lines. We present here a simple, powerful and broadly applicable method to generate new sublines of tumor cell lines to study loss of cell-cell adhesion in cancer progression.

Planar Microstrip Ring Resonators for Microwave-Based Gas Sensing: Design Aspects and Initial Transducers for Humidity and Ammonia Sensing.

A planar microstrip ring resonator structure on alumina was developed using the commercial FEM software COMSOL. Design parameters were evaluated, eventually leading to an optimized design of a miniaturized microwave gas sensor. The sensor was covered with a zeolite film. The device was successfully operated at around 8.5 GHz at room temperature as a humidity sensor. In the next step, an additional planar heater will be included on the reverse side of the resonator structure to allow for testing of gas-sensitive materials under sensor conditions.

Comparison of cancer cells in 2D vs 3D culture reveals differences in AKT-mTOR-S6K signaling and drug responses.

Three-dimensional (3D) cancer models are used as preclinical systems to mimic physiologic drug responses. We provide evidence for strong changes of proliferation and metabolic capacity in three dimensions by systematically analyzing spheroids of colon cancer cell lines. Spheroids showed relative lower activities in the AKT, mammalian target of rapamycin (mTOR) and S6K (also known as RPS6KB1) signaling pathway compared to cells cultured in two dimensions. We identified spatial alterations in signaling, as the level of phosphorylated RPS6 decreased from the spheroid surface towards the center, which closely coordinated with the tumor areas around vessels in vivo These 3D models displayed augmented anti-tumor responses to AKT-mTOR-S6K or mitogen-activated protein kinase (MAPK) pathway inhibition compared to those in 2D models. Inhibition of AKT-mTOR-S6K resulted in elevated ERK phosphorylation in 2D culture, whereas under these conditions, ERK signaling was reduced in spheroids. Inhibition of MEK1 (also known as MAP2K1) led to decreased AKT-mTOR-S6K signaling in 3D but not in 2D culture. These data indicate a distinct rewiring of signaling in 3D culture and during treatment. Detached tumor-cell clusters in vessels, in addition to circulating single tumor cells, play a putative role in metastasis in human cancers. Hence, the understanding of signaling in spheroids and the responses in the 3D models upon drug treatment might be beneficial for anti-cancer therapies.

Symbiotic Fungi Control Plant Root Cortex Development through the Novel GRAS Transcription Factor MIG1.

In an approaching scenario of soil nutrient depletion, root association with soil microorganisms can be key for plant health and sustainability [1-3]. Symbiotic arbuscular mycorrhizal (AM) fungi are major players in helping plants growing under nutrient starvation conditions. They provide plants with minerals like phosphate and, furthermore, act as modulators of plant growth altering the root developmental program [4, 5]. However, the precise mechanisms involved in this latter process are not well understood. Here, we show that AM fungi are able to modulate root cortex development in Medicago truncatula by activating a novel GRAS-domain transcription factor, MIG1, that determines the size of cortical root cells. MIG1 expression peaks in arbuscule-containing cells, suggesting a role in cell remodeling during fungal accommodation. Roots ectopically expressing MIG1 become thicker due to an increase in the number and width of cortical cells. This phenotype is fully counteracted by gibberellin (GA) and phenocopied with a GA biosynthesis inhibitor or by expression of a dominant DELLA (Δ18DELLA1) protein. MIG1 downregulation leads to malformed arbuscules, a phenotype rescued by Δ18DELLA1, suggesting that MIG1 intersects with the GA signaling to control cell morphogenesis through DELLA1. DELLA1 was shown to be a central node controlling arbuscule branching [6-8]. Now we provide evidence that, together with MIG1, DELLA1 is responsible for radial cortical cell expansion during arbuscule development. Our data point toward DELLA proteins being not only longitudinal root growth repressors [9] but also positive regulators of cortical radial cell expansion, extending the knowledge of how DELLAs control root growth.