The distinct gene regulatory network of myoglobin in prostate and breast cancer

Myoglobin (MB) is not only strongly expressed in myocytes, but also at much lower levels in different cancer entities. 40% of breast tumors are MB-positive, with the globin being co-expressed with markers of tumor hypoxia in a proportion of cases. In breast cancer, MB expression is associated with a positive hormone receptor status and patient prognosis. In prostate cancer, another hormone-dependent cancer type, 53% of tumors were recently shown to express MB. Especially in more aggressive prostate cancer specimen MB expression also correlates with increased patient survival rates. Both findings might be due to tumor-suppressing properties of MB in cancer cells. In contrast to muscle, MB transcription in breast and prostate cancer mainly depends on a novel, alternative promoter site. We show here that its associated transcripts can be upregulated by hypoxia and downregulated by estrogens and androgens in MCF7 breast and LNCaP prostate cancer cells, respectively. Bioinformatic data mining of epigenetic histone marks and experimental verification reveal a hitherto uncharacterized transcriptional network that drives the regulation of the MB gene in cancer cells. We identified candidate hormone-receptor binding elements that may interact with the cancer-associated MB promoter to decrease its activity in breast and prostate cancer cells. Additionally, a regulatory element, 250 kb downstream of the promoter, acts as a hypoxia-inducible site within the transcriptional machinery. Understanding the distinct regulation of MB in tumors will improve unraveling the respiratory protein’s function in the cancer context and may provide new starting points for developing therapeutic strategies

Patient experiences of nurse-facilitated advance care planning in a general practice setting: a qualitative study

Background: Advance care planning (ACP) can offer benefits to patients and their families, especially when delivered in outpatient settings, but uptake remains low. Common barriers for health professionals include a perceived lack of time and adequate training, experience, and confidence in conducting ACP. Patient-reported barriers include a lack of awareness of ACP or discomfort initiating or engaging in discussions about end-of-life. Methods: We aimed to explore patients\u27 perspectives of an ACP intervention designed to address common barriers to uptake in the general practice setting. We provided training and support to doctors and general practice nurses (GPNs) to initiate and lead ACP discussions at their respective practices (2014 to 2015). Following the intervention, we conducted interviews with patients to explore their experience of engaging in ACP in the general practice setting. Thematic analysis was used to inductively code transcripts and identify key themes from semi-structured interviews with patients. Results: Six major themes relating to patient experiences of GPN-facilitated ACP were identified: Working through ideas, therapeutic relationship with nurses, significance of making wishes known, protecting family from burden, autonomy in decision-making, and challenges of family communication. The patients valued the opportunity to speak about issues that are important to them with the GPN who they found to be compassionate and caring. The patients felt that ACP would lead to significant benefits not only to themselves but also for their family. Despite encouragement to involve other family members, most patients attended the ACP discussions alone or as a couple; many did not see the relevance of their family being involved in the discussions. Some patients felt uncomfortable or reluctant in communicating the results of their discussion with their family. Conclusions: With adequate training and support, GPNs are able to initiate and facilitate ACP conversations with patients. Their involvement in ACP can have significant benefits for patients. Psychosocial and relational elements of care are critical to patient satisfaction. Our findings show that some patients may feel uncomfortable or reluctant to communicate the results of their ACP discussions with their family. A future larger study is required to verify the findings of this pilot study

Urinary neurotransmitter analysis and canine behavior assessment

Behavioral problems are highly prevalent in domestic dogs, negatively affecting the quality of life of dogs and their owners. In humans and dogs, neuropsychological or neurobehavioral disorders can be associated with deviations in various neurotransmitter systems. Previous evidence has revealed correlations between urinary neurotransmitters and various behavioral disorders; however, a causal relationship has not yet been conclusively demonstrated. Non-invasive urinary neurotransmitter analysis may identify specific biomarkers, which enable a more differentiated assessment of canine behavioral disorders in the future and contribute to more effective neuromodulatory treatment decisions and monitoring. This approach could offer new insights into underlying pathomechanisms of canine neurobehavioral disorders. This study assessed urinary neurotransmitter levels and the descriptive behavior profile of 100 dogs using established rating scales (Canine Behavioral Assessment and Research Questionnaire, Attention Deficit Hyperactivity Disorder Rating Scale, Dog Personality Questionnaire, Canine Cognitive Dysfunction Rating Scale), and explored relationships between these variables. No correlation was found between urinary neurotransmitters and the assessed behavior profiles; however, age-, sex- and neuter-related influences were identified. The lack of correlation could be explained by the many confounding factors influencing both behavior and urinary neurotransmitter excretion, including age, sex and neuter status effects, and methodological issues e.g., low discriminatory power between anxiety and aggression in the descriptive behavior evaluation. Urinary neurotransmitter testing could not be validated as a tool for canine behavior evaluation in this study. However, reliable assessment methods with low susceptibility to human biases could be valuable in the future to support behavioral-phenotype diagnoses

Sixty-seven species newly recorded for the flora of Angola: recent findings from vegetation surveys and herbarium collections

Angola is a tropical country with many biogeographical units and, therefore, has a high floristic diversity. Although an increasing number of floristic studies has been carried out in Angola in recent years, the country is still considered to be underinvestigated as many species being collected were previously unknown there. Several scientific groups working in different parts of Angola contributed to this paper their data from biodiversity assessments. With this we can add 67 species newly recorded for Angola, including two new generic records and five alien species, to the almost 7,300 vascular plant taxa known so far for Angola. Most of the new records for Angola are also present in different neighbouring countries, but they are little known, and their IUCN threat status has not been assessed yet. However, ongoing fieldwork and exploration are needed to complete the floristic knowledge of the understudied country

Can Urban Air Mobility become reality? Opportunities, challenges and selected research results

Urban Air Mobility (UAM) is a new air transportation system for passengers and cargo in urban environments, enabled by new technologies and integrated into multimodal transportation systems. The vision of UAM comprises the mass use in urban and suburban environments, complementing existing transportation systems and contributing to the decarbonization of the transport sector. Initial attempts to create a market for urban air transportation in the last century failed due to lack of profitability and community acceptance. Technological advances in numerous fields over the past few decades have led to a renewed interest in urban air transportation. UAM is expected to benefit users and to also have a positive impact on the economy by creating new markets and employment opportunities for manufacturing and operation of UAM vehicles and the construction of related ground infrastructure. However, there are also concerns about noise, safety and security, privacy and environmental impacts. Therefore, the UAM system needs to be designed carefully to become safe, affordable, accessible, environmentally friendly, economically viable and thus sustainable. This paper provides an overview of selected key research topics related to UAM and how the German Aerospace Center (DLR) contributed to this research in the project "HorizonUAM - Urban Air Mobility Research at the German Aerospace Center (DLR)". Selected research results that support the realization of the UAM vision are briefly presented.Comment: 20 pages, 7 figures, project HorizonUA

Coordinated RhoA signaling at the leading edge and uropod is required for T cell transendothelial migration

A biosensor for the RhoA GTPase illustrates its activation patterns in both the front and rear of migrating lymphocytes

Expert considerations and consensus for using dogs to detect human SARS-CoV-2-infections

Funding Information: This Open Access publication was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 491094227 “Open Access Publication Funding” and the University of Veterinary Medicine Hannover, Foundation.Peer reviewe

SU(VAR)3-7 Links Heterochromatin and Dosage Compensation in Drosophila

In Drosophila, dosage compensation augments X chromosome-linked transcription in males relative to females. This process is achieved by the Dosage Compensation Complex (DCC), which associates specifically with the male X chromosome. We previously found that the morphology of this chromosome is sensitive to the amounts of the heterochromatin-associated protein SU(VAR)3-7. In this study, we examine the impact of change in levels of SU(VAR)3-7 on dosage compensation. We first demonstrate that the DCC makes the X chromosome a preferential target for heterochromatic markers. In addition, reduced or increased amounts of SU(VAR)3-7 result in redistribution of the DCC proteins MSL1 and MSL2, and of Histone 4 acetylation of lysine 16, indicating that a wild-type dose of SU(VAR)3-7 is required for X-restricted DCC targeting. SU(VAR)3-7 is also involved in the dosage compensated expression of the X-linked white gene. Finally, we show that absence of maternally provided SU(VAR)3-7 renders dosage compensation toxic in males, and that global amounts of heterochromatin affect viability of ectopic MSL2-expressing females. Taken together, these results bring to light a link between heterochromatin and dosage compensation

Can Urban Air Mobility become reality? Opportunities and challenges of UAM as innovative mode of transport and DLR contribution to ongoing research

Urban Air Mobility (UAM) is a new air transportation system for passengers and cargo in urban environments, enabled by new technologies and integrated into multimodal transportation systems. The vision of UAM comprises the mass use in urban and suburban environments, complementing existing transportation systems and contributing to the decarbonization of the transport sector. Initial attempts to create a market for urban air transportation in the last century failed due to lack of profitability and community acceptance. Technological advances in numerous fields over the past few decades have led to a renewed interest in urban air transportation. UAM is expected to benefit users and to also have a positive impact on the economy by creating new markets and employment opportunities for manufacturing and operation of UAM vehicles and the construction of related ground infrastructure. However, there are also concerns about noise, safety and security, privacy and environmental impacts. Therefore, the UAM system needs to be designed carefully to become safe, affordable, accessible, environmentally friendly, economically viable and thus sustainable. This paper provides an overview of selected key research topics related to UAM and how the German Aerospace Center (DLR) contributed to this research in the project "HorizonUAM - Urban Air Mobility Research at the German Aerospace Center (DLR)". Selected research results on the topics of market potential and public acceptance, vehicle design (including battery degradation, onboard systems, cabin design, cabin simulation), infrastructure, operations (including U-space, safe autonomy, navigation, communication, cost modeling) and overall system modeling are briefly presented