Untersuchung von Chloroplastenfunktion mit Hilfe differentieller Genexpressionsanalyse

Die Chloroplasten haben als Folge ihrer Entwicklung vom ehemals frei lebenden Cyanobakterium hin zum biosynthetischen Zellorganell einer eukaryotischen Zelle die Fähigkeit verloren, alle zum Leben beziehungsweise zum Überleben benötigten Proteine selbstständig zu synthetisieren. Die postendosymbiontische Evolution des Proto-Chloroplasten war geprägt von einem massiven Gentransfer in den Zellkern, so dass mehr als 90 % des Proteoms heutiger Chlorplasten kernkodiert und dadurch auch die Regulation der Chloroplastenfunktionen größtenteils auf den Zellkern übergegangen ist. Die Entwicklung eines vollständig funktionellen Chloroplasten ist somit abhängig von der koordinierten Expression von kernkodierten und plastomkodierten Genen als Antwort auf sowohl entwicklungsspezifische als auch umgebungsbedingte Signale. Die Regulation der Transkription dieser Gene ist eine effektive Methode, um Einfluss auf die Funktionen des Chloroplasten zu nehmen. Die Transkriptionsregulation einer Reihe von Genen des Kerns, insbesondere des zu annähernd gleichen Teilen im Kern und Plastom kodierten photosynthetischen Apparates, ist abhängig von der Präsenz funktioneller Plastiden in der Zelle und beinhaltet retrograde Signale, die vom Chloroplasten zum Zellkern gerichtet sind. In dieser Arbeit wurde durch einen Makroarray die differentielle Expression von 3292 nukleären Genen, die größtenteils Proteine des Plastiden kodieren und fast das vollständige kernkodierte Transkriptom des Chloroplasten darstellen, unter 101 verschiedenen Bedingungen untersucht. Eine gemeinsame Schnittmenge von 1616 konstitutiv exprimierten Genen zeigte nur drei übergeordnete Hauptklassen der transkriptionellen Antwort. Die meisten der getesteten Stimuli resultieren in entweder vorherrschend induzierte Transkription oder aber vorherrschend reprimierte Transkription der meisten und überwiegend jeweils identischen Gene dieses Teils des plastidären Transkriptoms. Anscheinend existiert ein integrativer Hauptschalter, der das nukleäre Transkriptom des Chloroplasten als ein Ganzes reguliert. Anhand ihres Expressionsverhaltens ließen sich die 1616 Gene in 25 voneinander separierte, ko-exprimierte Gruppen (Regulons) einteilen. Ausgenommen der Regulons SOM 4-1 und SOM 5-1 sind alle anderen Regulons heterogen und beinhalten Gene, die Proteine unterschiedlicher subzellulärer Lokalisationen und verschiedener bioche-mischer Funktionen kodieren. Das lässt darauf schließen, dass die verschiedenen Zellorganellen und/oder verschiedenste Stoffwechselwege der Zelle zumindest auf der Ebene der Transkription im Zellkern koordiniert sind. Die Ausnahme sind die Gene des Kerngenoms, die die Untereinheiten des Photosynthese-Apparates oder aber Proteine, die beteiligt sind an der Transkriptions- und Translationsmaschinerie der plastomkodierten Gene (insbesondere Ribosomen-Untereinheiten) (Regulon SOM 4-1 und Regulon SOM 5-1) kodieren. Die Ko-Expression dieser Gene deutet darauf hin, dass ein bisher unbekannter Mechanismus, möglicherweise über die nukleäre Kontrolle der Ribosomen-Abundanz im Cloroplasten, die Genexpression gerade des Teils des Proteoms koordiniert, der noch immer sowohl im Kern als auch im Plastom kodiert ist. Die Ergebnisse aus den Expressionsanalysen unterstützen zudem die Vermutung, dass die retrograden Signale vom Organell zum Zellkern an der Regulation der nukleären Transkription maßgeblich beteiligt sind. Die Ko-Regulation der Gene der Photosynthese und der ribosomalen Proteine des Chloroplasten entzieht sich der oben dargestellten generellen Expressionsregulation von nukleären Chloroplastengenen, die kontrolliert wird durch einen kürzlich beschriebenen transkriptionellen Hauptschalter. Durch den Vergleich zu anderen Chloroplasten-funktionen zeigt diese Beobachtung die Existenz eines speziellen Modus der transkriptionellen Regulation der Photosynthese an. Aus der evolutionären Sicht deuten diese Ergebnisse darauf hin, dass die funktionelle Integration des Proto-Chloroplasten in die eukaryotische Wirtszelle mit der Etablierung von verschiedenen Ebenen der nukleären Kontrolle der Transkription einherging

Inferring Feature Relevances From Metric Learning

Schulz A, Mokbel B, Biehl M, Hammer B. Inferring Feature Relevances From Metric Learning. In: 2015 IEEE Symposium Series on Computational Intelligence. Piscataway, NJ: IEEE; 2015

Tissue- and development-stage-specific mRNA and heterogeneous CNV signatures of human ribosomal proteins in normal and cancer samples.

Panda A, Yadav A, Yeerna H, et al. Tissue- and development-stage-specific mRNA and heterogeneous CNV signatures of human ribosomal proteins in normal and cancer samples. Nucleic acids research. 2020.We give results from a detailed analysis of human Ribosomal Protein (RP) levels in normal and cancer samples and cell lines from large mRNA, copy number variation and ribosome profiling datasets. After normalizing total RP mRNA levels per sample, we find highly consistent tissue specific RP mRNA signatures in normal and tumor samples. Multiple RP mRNA-subtypes exist in several cancers, with significant survival and genomic differences. Some RP mRNA variations among subtypes correlate with copy number loss of RP genes. In kidney cancer, RP subtypes map to molecular subtypes related to cell-of-origin. Pan-cancer analysis of TCGA data showed widespread single/double copy loss of RP genes, without significantly affecting survival. In several cancer cell lines, CRISPR-Cas9 knockout of RP genes did not affect cell viability. Matched RP ribosome profiling and mRNA data in humans and rodents stratified by tissue and development stage and were strongly correlated, showing that RP translation rates were proportional to mRNA levels. In a small dataset of human adult and fetal tissues, RP protein levels showed development stage and tissue specific heterogeneity of RP levels. Our results suggest that heterogeneous RP levels play a significant functional role in cellular physiology, in both normal and disease states. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research

Formative sociology and ethico-political imaginaries: opening up transnational responses to Palestine–Israel

Recent contributors to this journal have sought to radicalise sociology by exploring how the discipline might expand political imaginaries and take up non-reductionist notions of everyday ethics. In a related move, sociologists are exploring the performative potential of sociological practices and sensibilities, while anthropologists are reframing the relationship of ethnography to theory. This article contributes to these projects by focusing on an acute case in which an expanded political imaginary is urgently needed; the tensions between political solidarity and ethical violence in transnational communications around Palestine–Israel. Drawing on an ethnographic study of conflicting activist groups in Britain, I highlight a profound ethical problem: that claims for justice appear to entail a violent refusal to acknowledge ‘the other’. The article examines how the dualistic logics structuring sociological imaginaries have occluded and reproduced this impasse, and focuses on an attempt by activists to create non-violent modes of solidarity. Articulating a role for ethnography in opening up this alternative, I show how responsive and creative sociological methods can bring new languages, imaginaries and political formations into being

The makeshift city: towards a global geography of squatting

This paper introduces a set of analytical frames that explore the possibilities of conceiving, researching and writing a global geography of squatting. The paper argues that it is possible to detect, in the most tenuous of urban settings, ways of thinking about and living urban life that have the potential to reanimate the city as a key site of geographical inquiry. The paper develops a modest theory of ‘urban combats’ to account for the complexity and provisionality of squatting as an informal set of practices, as a makeshift approach to housing and as a precarious form of inhabiting the city

Medical borderlands: engineering the body with plastic surgery and hormonal therapies in Brazil

"This paper explores medical borderlands where health and enhancement practices are entangled. It draws on fieldwork carried out in the context of two distinct research projects in Brazil on plastic surgery and sex hormone therapies. (...)

Implementation of a Virtual Interprofessional ICU Learning Collaborative: Successes, Challenges, and Initial Reactions From the Structured Team- Based Optimal Patient-Centered Care for Virus COVID-19 Collaborators

IMPORTANCE: Initial Society of Critical Care Medicine Discovery Viral Infection and Respiratory illness Universal Study (VIRUS) Registry analysis suggested that improvements in critical care processes offered the greatest modifiable opportunity to improve critically ill COVID-19 patient outcomes. OBJECTIVES: The Structured Team-based Optimal Patient-Centered Care for Virus COVID-19 ICU Collaborative was created to identify and speed implementation of best evidence based COVID-19 practices. DESIGN, SETTING, AND PARTICIPANTS: This 6-month project included volunteer interprofessional teams from VIRUS Registry sites, who received online training on the Checklist for Early Recognition and Treatment of Acute Illness and iNjury approach, a structured and systematic method for delivering evidence based critical care. Collaborators participated in weekly 1-hour videoconference sessions on high impact topics, monthly quality improvement (QI) coaching sessions, and received extensive additional resources for asynchronous learning. MAIN OUTCOMES AND MEASURES: Outcomes included learner engagement, satisfaction, and number of QI projects initiated by participating teams. RESULTS: Eleven of 13 initial sites participated in the Collaborative from March 2, 2021, to September 29, 2021. A total of 67 learners participated in the Collaborative, including 23 nurses, 22 physicians, 10 pharmacists, nine respiratory therapists, and three nonclinicians. Site attendance among the 11 sites in the 25 videoconference sessions ranged between 82% and 100%, with three sites providing at least one team member for 100% of sessions. The majority reported that topics matched their scope of practice (69%) and would highly recommend the program to colleagues (77%). A total of nine QI projects were initiated across three clinical domains and focused on improving adherence to established critical care practice bundles, reducing nosocomial complications, and strengthening patient- and family-centered care in the ICU. Major factors impacting successful Collaborative engagement included an engaged interprofessional team; an established culture of engagement; opportunities to benchmark performance and accelerate institutional innovation, networking, and acclaim; and ready access to data that could be leveraged for QI purposes. CONCLUSIONS AND RELEVANCE: Use of a virtual platform to establish a learning collaborative to accelerate the identification, dissemination, and implementation of critical care best practices for COVID-19 is feasible. Our experience offers important lessons for future collaborative efforts focused on improving ICU processes of care

2019 Proceedings of the 2nd International Conference on Trauma Surgery Technology in Giessen (Germany)

It is now for a second time that we can invite researchers to come to Giessen for an international exchange of the latest research and a discussion of ideas. This year again, the Deutsche Forschungsgemeinschaft (DFG) is sponsoring the event. The main topic for 2019 is 'Vibration in antibacterial and oncological therapy'. Many effects of mechanical vibration on tissue have been discovered so far. Clinical applications relying on vibration exist for a variety of conditions. The intracellular processes, however, are still largely not understood. And reproducibility remains a matter of potential for improvement. DFG funds for the 3rd conference in 2020 have already been approved for a focus on multifunctional trauma surgery implants.Deutsche Forschungsgemeischaft (DFG), German

Global, regional, and national sex-specific burden and control of the HIV epidemic, 1990-2019, for 204 countries and territories: the Global Burden of Diseases Study 2019

Background: The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic. Methods: To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal care-clinic sentinel surveillance data were available. For the remaining 156 of 204 locations, we developed a cohort-incidence bias adjustment to derive incidence as a function of cause-of-death data from vital registration systems. The incidence was input to a custom Spectrum model. To assess progress, we measured the percentage change in incident cases and deaths between 2010 and 2019 (threshold >75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold <0·03), and the ratio of incident cases to deaths (incidence-to-mortality ratio threshold <1·0). Findings: In 2019, there were 36·8 million (95% uncertainty interval [UI] 35·1–38·9) people living with HIV worldwide. There were 0·84 males (95% UI 0·78–0·91) per female living with HIV in 2019, 0·99 male infections (0·91–1·10) for every female infection, and 1·02 male deaths (0·95–1·10) per female death. Global progress in incident cases and deaths between 2010 and 2019 was driven by sub-Saharan Africa (with a 28·52% decrease in incident cases, 95% UI 19·58–35·43, and a 39·66% decrease in deaths, 36·49–42·36). Elsewhere, the incidence remained stable or increased, whereas deaths generally decreased. In 2019, the global incidence-to-prevalence ratio was 0·05 (95% UI 0·05–0·06) and the global incidence-to-mortality ratio was 1·94 (1·76–2·12). No regions met suggested thresholds for progress. Interpretation: Sub-Saharan Africa had both the highest HIV burden and the greatest progress between 1990 and 2019. The number of incident cases and deaths in males and females approached parity in 2019, although there remained more females with HIV than males with HIV. Globally, the HIV epidemic is far from the UNAIDS benchmarks on progress metrics. Funding: The Bill & Melinda Gates Foundation, the National Institute of Mental Health of the US National Institutes of Health (NIH), and the National Institute on Aging of the NIH

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens