SNF1-RELATED KINASE 1 and TARGET OF RAPAMYCIN control light-responsive splicing events and developmental characteristics in etiolated Arabidopsis seedlings.

The kinases SNF1-RELATED KINASE 1 (SnRK1) and TARGET OF RAPAMYCIN (TOR) are central sensors of the energy status, linking this information via diverse regulatory mechanisms to plant development and stress responses. Despite the well-studied functions of SnRK1 and TOR under conditions of limited or ample energy availability, respectively, little is known about the extent to which the 2 sensor systems function and how they are integrated in the same molecular process or physiological context. Here, we demonstrate that both SnRK1 and TOR are required for proper skotomorphogenesis in etiolated Arabidopsis (Arabidopsis thaliana) seedlings, light-induced cotyledon opening, and regular development in light. Furthermore, we identify SnRK1 and TOR as signaling components acting upstream of light- and sugar-regulated alternative splicing events, expanding the known action spectra for these 2 key players in energy signaling. Our findings imply that concurring SnRK1 and TOR activities are required throughout various phases of plant development. Based on the current knowledge and our findings, we hypothesize that turning points in the activities of these sensor kinases, as expected to occur upon illumination of etiolated seedlings, instead of signaling thresholds reflecting the nutritional status may modulate developmental programs in response to altered energy availability.

Alternative Splicing Substantially Diversifies the Transcriptome during Early Photomorphogenesis and Correlates with the Energy Availability in Arabidopsis.

Plants use light as source of energy and information to detect diurnal rhythms and seasonal changes. Sensing changing light conditions is critical to adjust plant metabolism and to initiate developmental transitions. Here, we analyzed transcriptome-wide alterations in gene expression and alternative splicing (AS) of etiolated seedlings undergoing photomorphogenesis upon exposure to blue, red, or white light. Our analysis revealed massive transcriptome reprogramming as reflected by differential expression of ∼20% of all genes and changes in several hundred AS events. For more than 60% of all regulated AS events, light promoted the production of a presumably protein-coding variant at the expense of an mRNA with nonsense-mediated decay-triggering features. Accordingly, AS of the putative splicing factor REDUCED RED-LIGHT RESPONSES IN CRY1CRY2 BACKGROUND1, previously identified as a red light signaling component, was shifted to the functional variant under light. Downstream analyses of candidate AS events pointed at a role of photoreceptor signaling only in monochromatic but not in white light. Furthermore, we demonstrated similar AS changes upon light exposure and exogenous sugar supply, with a critical involvement of kinase signaling. We propose that AS is an integration point of signaling pathways that sense and transmit information regarding the energy availability in plants.

Bone evaluation study-2: update on the epidemiology of osteoporosis in Germany.

Osteoporosis is the most common bone disorder. Our data gives an estimate of around 5.87 million cases of osteoporosis in the general German population in 2018. Only 30% of insured individuals who suffered an osteoporotic fracture and/or had a confirmed diagnosis of osteoporosis, received an appropriate prescription. PURPOSE: Osteoporosis is the most common bone disorder. It particularly affects elderly people and increases the risk of atraumatic fractures. The aim of this study was to estimate the prevalence of osteoporosis in the general German population aged ≥ 50 years and to collect data on the frequency of prescription of osteoporosis-specific medication in order to assess the treatment gap. METHODS: Retrospective analysis of anonymized data of individuals aged ≥ 50 years insured under statutory healthcare schemes from the database of the Institute for Applied Health Research Berlin (InGef) for 2018 (study population). Insured individuals with osteoporosis were identified based on osteoporosis diagnoses, osteoporosis-specific prescriptions, or osteoporotic fractures. Thus, we estimated the prevalence of osteoporosis in the general German population aged ≥ 50 years. The prevalence of diagnoses, fractures, and prescriptions was determined for the study population and stratified by age and gender. RESULTS: Within the study population of 1,599,299 insured individuals, a prevalence of osteoporosis of 15.9% was determined. This estimated approximately 5.87 million cases of osteoporosis for the general German population. 81.6% of the cases were women. Osteoporosis-specific prescriptions were received by 30.0% of the insured individuals in the study population who had been diagnosed with osteoporosis and/or suffered an osteoporotic fracture. CONCLUSIONS: Germany has a high prevalence of osteoporosis. Only a small portion of individuals who may require osteoporosis-specific treatment actually receive it.

Epidemiology and treatment of pain associated with osteoarthritis of the knee in Germany: A retrospective health claims data analysis.

Objective: Osteoarthritis of the knee (knee OA) is a serious joint disease leading to pain and reduced quality of life. Pharmacological treatments include anti-inflammatories, analgesics, intraarticular hyaluronic acid, and intraarticular corticosteroids while for severe knee OA, knee replacement is an option. This study examined the incidence, prevalence, patient characteristics, and uptake of medical and surgical treatments in knee OA patients in Germany. Design: A non-interventional, retrospective health claims data analysis with anonymized data from the InGef database was performed. Patients ≥18 years were analyzed cross-sectionally for each year 2015-2020. Newly diagnosed patients in 2015 were also longitudinally analyzed until end of 2020. Results: Annual knee OA prevalence increased from 7.07 â€‹% in 2015 to 7.39 â€‹% in 2020. Annual incidence proportions ranged from 1.71 â€‹% in 2015 to 1.46 â€‹% in 2020. Knee replacement was the most common surgery, with rising patient numbers (e.g., 7918 patients in 2015 and 8975 patients in 2019). Approximately 62 â€‹% of patients newly diagnosed in 2015 received prescription pharmacological pain treatment during follow-up. Most (96.95 â€‹%) received non-opioid analgesics, followed by weak opioids (8.14 â€‹%) and strong opioids (3.00 â€‹%) as first-line treatment (combinations possible). Knee surgery was performed in 16.6 â€‹% of patients during follow-up. Median time from first diagnosis until surgery was 346 days for any knee surgery and 564 days for knee replacement. Conclusions: The number of patients with knee OA in Germany is steadily rising, along with an increasing number of surgical interventions, especially knee replacement. Time until first surgery and knee replacement is relatively short, even for newly diagnosed patients.