Paired NLR receptors: Interplay of RPS4 and RRS1 in Arabidopsis immunity

Plants have evolved intracellular NLR receptors to recognize pathogen effectors and trigger a robust immune response (ETI). The Arabidopsis NLR gene pair RPS4 (Resistance to Pseudomonas syringae 4) and RRS1 (Resistance to Ralstonia solanacearum 1) cooperates genetically and physically to recognize, amongst others, the Pseudomonas syringae effector AvrRps4. A second RPS4/RRS1-like gene pair (RPS4b/RRS1b) contributes to AvrRps4 recognition. Transient or stable overexpression of RPS4, but not RRS1 induces immunity, and RPS4, but not RRS1 depends on a canonical ATP-binding pocket for its function. Also, RRS1 interacts with both RPS4 and pathogen effectors, suggesting a model where RRS1 as a sensor recognizes effectors and conveys the information to the executor RPS4, releasing it from RRS1 negative regulation to trigger immunity. However, RRS1 contributes to effector-independent autoimmunity in RPS4 overexpressing Arabidopsis, indicating an additional positive regulatory function apart from the suggested effector sensing. The work presented here re-evaluates the role of RRS1 in RPS4 induced signaling. In the absence of both RRS1a and RRS1b, RPS4 autoimmunity such as plant stunting and transcriptional reprogramming is decreased. Also, RPS4 protein accumulation is substantially reduced without RRS1, suggesting RRS1 positively contributes to RPS4 induced signaling by stabilizing RPS4 to allow sufficient immune complex formation. To gain insight into these RPS4-associated immune complexes and to connect RPS4 activation with defense outputs like cell death and transcriptional reprogramming, RPS4 co-purified proteins in pre- and post-activation complexes were analyzed by mass-spectrometry. Identified candidates are involved in processes such as protein synthesis and stability control, redox regulation and secretion. Their potential roles in immunity are discussed in this study. For several NLR receptors, nuclear localization is necessary for defense activation, and recently direct interactions between NLRs and transcription factors were reported, pointing at a close connection of these NLRs, including RPS4, to the chromatin. RRS1 contains a C-terminal WRKY transcription factor domain, and disruption of its DNA binding causes autoimmunity in the Arabidopsis slh1 mutant. To unravel the importance and dynamics of RRS1 DNA-association in plant immunity, transgenic RRS1 lines were characterized and used for chromatin-immunoprecipitation (ChIP). To allow conclusive evaluation of ChIP results, targeted mutations were inserted into RRS1 to generate loss- or gain-of-function alleles as ChIP controls. Summarizing published information and data obtained from this work, a new model of RPS4 and RRS1 interaction is discussed where distinct immune complexes are formed in different cellular compartments to mediate cell death in the cytoplasm and transcriptional reprogramming in the nucleus

Corona viruses: reaching far beyond the common cold

Background: Human coronaviruses (HCoVs) are one of the most common causes of the \u201ccommon cold\u201d. Some HCoV strains, however, can cause fatal respiratory disease. Some examples of these diseases are severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Coronavirus Disease 19 (COVID-19). This article will review the etiology, clinical features, diagnosis, and management of HCoVs. Methods: A systematic literature review was performed using the terms \u201chuman coronaviruses\u201d, \u201cMERS-CoV\u201d, \u201cSARSCoV\u201d, \u201cSARS-CoV2\u201d, \u201cCOVID-19\u201d, and \u201ccommon cold\u201d in OVID MEDLINE, PubMed, and Cochrane Library. Findings: Most HCoVs cause mild upper respiratory infections which resolve with supportive care and no sequelae. In recent decades, however, there have been outbreaks of novel HCoVs that cause more severe disease. This is largely due to HCoVs having large genomes which undergo frequent recombination events, leading to the emergence of novel and more virulent strains of the virus. These severe respiratory illnesses can lead to acute respiratory distress requiring invasive intervention, such as mechanical ventilation. These severe infections can lead to long-lasting sequelae in patients. Scientists continue to investigate potential treatments for these viruses, though supportive care remains the gold standard. Scientists have succeeded in developing numerous vaccines for the SARS-CoV-2 virus, and ongoing data collection and analysis will shed even more light on the next steps in fighting the COVID-19 pandemic. Conclusion: Due to the frequency of recombination events and the subsequent emergence of novel strains, HCoVs are becoming more prevalent, making them a global health concern as they can lead to epidemics and pandemics. Understanding the epidemiology, etiology, clinical features, diagnosis, and management of HCoVs is important, especially during this worldwide pandemic

Investigation, testing, and development of an electron-bombardment ion engine system final report, mar. 3 - dec. 14, 1964

Electron bombardment, mercury-fueled ion engine system - investigation, testing, and development progra

Spatial, temporal and interindividual epigenetic variation of functionally important DNA methylation patterns

DNA methylation is an epigenetic modification that plays an important role in gene regulation. It can be influenced by stochastic events, environmental factors and developmental programs. However, little is known about the natural variation of gene-specific methylation patterns. In this study, we performed quantitative methylation analyses of six differentially methylated imprinted genes (H19, MEG3, LIT1, NESP55, PEG3 and SNRPN), one hypermethylated pluripotency gene (OCT4) and one hypomethylated tumor suppressor gene (APC) in chorionic villus, fetal and adult cortex, and adult blood samples. Both average methylation level and range of methylation variation depended on the gene locus, tissue type and/or developmental stage. We found considerable variability of functionally important methylation patterns among unrelated healthy individuals and a trend toward more similar methylation levels in monozygotic twins than in dizygotic twins. Imprinted genes showed relatively little methylation changes associated with aging in individuals who are >25 years. The relative differences in methylation among neighboring CpGs in the generally hypomethylated APC promoter may not only reflect stochastic fluctuations but also depend on the tissue type. Our results are consistent with the view that most methylation variation may arise after fertilization, leading to epigenetic mosaicism