Structure-Function Analysis of STRUBBELIG, an Arabidopsis Atypical Receptor-Like Kinase Involved in Tissue Morphogenesis

Tissue morphogenesis in plants requires the coordination of cellular behavior across clonally distinct histogenic layers. The underlying signaling mechanisms are presently being unraveled and are known to include the cell surface leucine-rich repeat receptor-like kinase STRUBBELIG in Arabidopsis. To understand better its mode of action an extensive structure-function analysis of STRUBBELIG was performed. The phenotypes of 20 EMS and T-DNA-induced strubbelig alleles were assessed and homology modeling was applied to rationalize their possible effects on STRUBBELIG protein structure. The analysis was complemented by phenotypic, cell biological, and pharmacological investigations of a strubbelig null allele carrying genomic rescue constructs encoding fusions between various mutated STRUBBELIG proteins and GFP. The results indicate that STRUBBELIG accepts quite some sequence variation, reveal the biological importance for the STRUBBELIG N-capping domain, and reinforce the notion that kinase activity is not essential for its function in vivo. Furthermore, individual protein domains of STRUBBELIG cannot be related to specific STRUBBELIG-dependent biological processes suggesting that process specificity is mediated by factors acting together with or downstream of STRUBBELIG. In addition, the evidence indicates that biogenesis of a functional STRUBBELIG receptor is subject to endoplasmic reticulum-mediated quality control, and that an MG132-sensitive process regulates its stability. Finally, STRUBBELIG and the receptor-like kinase gene ERECTA interact synergistically in the control of internode length. The data provide genetic and molecular insight into how STRUBBELIG regulates intercellular communication in tissue morphogenesis

DETORQUEO, QUIRKY, and ZERZAUST Represent Novel Components Involved in Organ Development Mediated by the Receptor-Like Kinase STRUBBELIG in Arabidopsis thaliana

Intercellular signaling plays an important role in controlling cellular behavior in apical meristems and developing organs in plants. One prominent example in Arabidopsis is the regulation of floral organ shape, ovule integument morphogenesis, the cell division plane, and root hair patterning by the leucine-rich repeat receptor-like kinase STRUBBELIG (SUB). Interestingly, kinase activity of SUB is not essential for its in vivo function, indicating that SUB may be an atypical or inactive receptor-like kinase. Since little is known about signaling by atypical receptor-like kinases, we used forward genetics to identify genes that potentially function in SUB-dependent processes and found recessive mutations in three genes that result in a sub-like phenotype. Plants with a defect in DETORQEO (DOQ), QUIRKY (QKY), and ZERZAUST (ZET) show corresponding defects in outer integument development, floral organ shape, and stem twisting. The mutants also show sub-like cellular defects in the floral meristem and in root hair patterning. Thus, SUB, DOQ, QKY, and ZET define the STRUBBELIG-LIKE MUTANT (SLM) class of genes. Molecular cloning of QKY identified a putative transmembrane protein carrying four C2 domains, suggesting that QKY may function in membrane trafficking in a Ca2+-dependent fashion. Morphological analysis of single and all pair-wise double-mutant combinations indicated that SLM genes have overlapping, but also distinct, functions in plant organogenesis. This notion was supported by a systematic comparison of whole-genome transcript profiles during floral development, which molecularly defined common and distinct sets of affected processes in slm mutants. Further analysis indicated that many SLM-responsive genes have functions in cell wall biology, hormone signaling, and various stress responses. Taken together, our data suggest that DOQ, QKY, and ZET contribute to SUB-dependent organogenesis and shed light on the mechanisms, which are dependent on signaling through the atypical receptor-like kinase SUB

What We Learned about COVID-19 So Far? Notes from Underground

The novel coronavirus pandemic poses a major global threat to public health. Our knowledge concerning every aspect of COVID-19 is evolving rapidly, given the increasing data from all over the world. In this narrative review, the Turkish Thoracic Society Early Career Taskforce members aimed to provide a summary on recent literature regarding epidemiology, clinical findings, diagnosis, treatment, prevention, and control of COVID-19. Studies revealed that the genetic sequence of the novel coronavirus showed significant identity to SARS-CoV and MERS-CoV. Angiotensin-converting enzyme 2 receptor is an important target of the SARS-CoV-2 while entering an organism. Smokers were more likely to develop the disease and have a higher risk for ICU admission. The mean incubation period was 6.4 days, whereas asymptomatic transmission was reported up to 25 days after infection. Fever and cough were the most common symptoms, and cardiovascular diseases and hypertension were reported to be the most common comorbidities among patients. Clinical manifestations range from asymptomatic and mild disease to severe acute respiratory distress syndrome. Several patients showed typical symptoms and radiological changes with negative RT-PCR but positive IgG and IgM antibodies. Although radiological findings may vary, bilateral, peripherally distributed, ground-glass opacities were typical of COVID-19. Poor prognosis was associated with older age, higher Sequential Organ Failure Assessment score, and high D-dimer level. Chloroquine was found to be effective in reducing viral replication in vitro. Likewise, protease inhibitors, including lopinavir/ritonavir, favipiravir, and nucleoside analogue remdesivir were proposed to be the potential drug candidates in COVID-19 management. Despite these efforts, we still have much to learn regarding the transmission, treatment, and prevention of COVID-19

COVID-19 Pandemic and the Global Perspective of Turkish Thoracic Society

It has been more than 3 months now since the first case of COVID-19 was reported in Turkey. Globally, the number of confirmed cases and deaths reached 9,653,048 and 491,128 respectively, as reported by 216 countries by June 27, 2020. Turkey had 1,396 new cases, 194,511 total cases, and 5,065 deaths by the same date. From the first case until today, the Turkish Thoracic Society (TTS) has been very proactive in educating doctors, increasing public awareness, undertaking academic studies, and assisting with public health policies. In the present report, social, academic, and management perspectives of the pandemic are presented under appropriate subtitles. During this critical public health crisis, TTS has once again demonstrated its readiness and constructive stance by supporting public health, healthcare workers, and the environment. This review summarizes the perspective of TTS on each aspect of the COVID-19 pandemic and casts light on its contributions

Eligibility of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator therapies: cohort of cystic fibrosis registry of Türkiye

Background. Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) variants are essential for determining eligibility for CFTR modulator drugs (CFTRms). In contrast to Europe and the USA, the treatment eligibility profile of cystic fibrosis (CF) patients in T & uuml;rkiye is not known. In this study we aimed to determine the eligibility of CF patients in T & uuml;rkiye for the CFTRms. Methods. The Cystic Fibrosis Registry of T & uuml;rkiye (CFrT) data was used to determine the age of patients in the year 2021 and the genetic variants they were carrying. Age- and CFTR-variant appropriate modulator therapies were determined using the Vertex (R) algorithm. Results. Among a total of 1930 registered patients, CTFR gene analysis was performed on a total of 1841 (95.4%) patients. Mutations were detected in one allele in 10.7% (198 patients), and in both alleles in 79% (1455 patients) of patients. A total of 855 patients (51.7% for whom at least 1 mutation was detected) were eligible for the drugs. The most appropriate drug among genotyped patients was found to be elexacaftor/tezacaftor/ivacaftor for 486 patients (26.4%), followed by ivacaftor for 327 patients (17.7%) and lumacaftor/ivacaftor for 42 patients (2%). Conclusions. Only half of patients registered in CFrT were eligible for CFTRms, which is a significant difference from the CFTR variant profile seen in USA and Europe. However, access to treatment is hampered for some patients whose genes are not analysed. Further studies in CF populations, where rare mutations are relatively more common, will contribute to the field of CFTR modulator treatments for such rare mutations

An extracellular network of Arabidopsis leucine-rich repeat receptor kinases

The cells of multicellular organisms receive extracellular signals using surface receptors. The extracellular domains (ECDs) of cell surface receptors function as interaction platforms, and as regulatory modules of receptor activation1,2. Understanding how interactions between ECDs produce signal-competent receptor complexes is challenging because of their low biochemical tractability3,4. In plants, the discovery of ECD interactions is complicated by the massive expansion of receptor families, which creates tremendous potential for changeover in receptor interactions5. The largest of these families in Arabidopsis thaliana consists of 225 evolutionarily related leucine-rich repeat receptor kinases (LRR-RKs)5, which function in the sensing of microorganisms, cell expansion, stomata development and stem-cell maintenance6,7,8,9. Although the principles that govern LRR-RK signalling activation are emerging1,10, the systems-level organization of this family of proteins is unknown. Here, to address this, we investigated 40,000 potential ECD interactions using a sensitized high-throughput interaction assay3, and produced an LRR-based cell surface interaction network (CSILRR) that consists of 567 interactions. To demonstrate the power of CSILRR for detecting biologically relevant interactions, we predicted and validated the functions of uncharacterized LRR-RKs in plant growth and immunity. In addition, we show that CSILRR operates as a unified regulatory network in which the LRR-RKs most crucial for its overall structure are required to prevent the aberrant signalling of receptors that are several network-steps away. Thus, plants have evolved LRR-RK networks to process extracellular signals into carefully balanced responses