Selection of Contrasting Parents for Drought Tolerance in Sunflower (Helianthus Annuus L.)

The aim of this research was select the best combination of contrasting parents to develop a mapping population for drought tolerance, based on phenotypic and genotypic data. Phenotyping was conducted in a greenhouse during 16 days at vegetative stage under well-watered (WW) and water-deficit (WD) conditions. Traits evaluated were: gain of leaf area (GLA), total water use (TWU), net assimilation rate (NAR), water use efficiency (WUE) and transpiration rate (TR) response to vapor pressure deficit (VPD) (slope and breakpoint). Genotyping was performed with 127 SSR markers and a cluster analyses was conducted. An important interaction was observed for NAR, WUE and breakpoint in the VPD response. Under WD conditions, all genotypes showed lower GLA and TWU, whereas NAR and WUE increased its values. All genotypes showed reduction of the slope and breakpoint in high VPD response on WD. PCA analysis explains the 80% of the total variability. PC1 discriminated HA89 and R419 due to a lower slope and higher breakpoint, while PC2 separated by water treatment based on the WUE and TWU values. Nighty nine SSR marker were amplified detecting 262 alleles. Cluster analyzes showed two main groups, one including HAR4 and B59 and the other one including five remaining genotypes. According to these results, only R419xHA64 and HA89xHAR4 had a greater genetic distance (1.08), besides a high polymorphism level between ILs (about 60%). Therefore, we conclude that these would be the best combination of contrasting parents to develop mapping populations for drought tolerance in sunflower.

Discovery of a Novel MyD88 Inhibitor M20 and Its Protection Against Sepsis-Mediated Acute Lung Injury

Myeloid differentiation factor 88 (MyD88) is a hub protein in the Toll-like receptor signaling pathway, which acts as a master switch for numerous inflammatory diseases, including acute lung injury (ALI). Although this protein is considered as a crucial therapeutic target, there are currently no clinically approved MyD88-targeting drugs. Based on previous literature, here we report the discovery via computer-aided drug design (CADD) of a small molecule, M20, which functions as a novel MyD88 inhibitor to efficiently relieve lipopolysaccharide-induced inflammation both in vitro and in vivo. Computational chemistry, surface plasmon resonance detection (SPR) and biological experiments demonstrated that M20 forms an important interaction with the MyD88-Toll/interleukin-1 receptor domain and thereby inhibits the protein dimerization. Taken together, this study found a MyD88 inhibitor, M20, with a novel skeleton, which provides a crucial understanding in the development and modification of MyD88 inhibitors. Meanwhile, the favorable bioactivity of the hit compound is also conducive to the treatment of acute lung injury or other more inflammatory diseases.

Molecular understanding of GPR120 agonist binding using homology modeling and molecular dynamics

The toll of type-2 diabetes and associated complications are continues, efforts to identify possible targets are ongoing. Free fatty acid receptor 4 (FFAR4/GPR120) has been recently identified to be a promising therapeutic target for a group of metabolic associated disorders. For the prevention of type 2 diabetes, significant scientific and commercial interest has been developed around GPR120 and its role. Due to the unavailability of a crystal structure, the interaction dynamics of GPR120 agonists were not yet determined to date. In the present study, we constructed the homology model for GPR120 and validated using available mutational data and molecular dynamics simulation, and explored its binding modes with known small molecule agonists. So, sixteen propionic acid derivatives as GPR120 agonists were collected to elucidate their binding modes. Experiential and theoretical studies suggested that the carboxylic group of ligands interact with Arg99, which is an important interaction for GPR120 activation. However, earlier reports also suggest that this interaction is not stable during the molecular dynamics simulation, which contradicts the experimental observations. Evidently, to refute this, we got a stable interaction of Arg99 with TUG891 and other recently reported 15 GPR120 agonists. In addition, we have also observed that in 1 µs molecular dynamics simulation Arg183 present in ECL2 tends to come inside and interact with ligand. Molecular dynamics simulation study provides a list of key hotspot residues which play an important role in ligand binding. The homology model and results provides could be further utilized as a powerful template to accelerate the research in this field.

Interactions between microbial diversity and substrate chemistry determine the fate of carbon in soil

Microbial decomposition drives the transformation of plant-derived substrates into microbial products that form stable soil organic matter (SOM). Recent theories have posited that decomposition depends on an interaction between SOM chemistry with microbial diversity and resulting function (e.g., enzymatic capabilities, growth rates). Here, we explicitly test these theories by coupling quantitative stable isotope probing and metabolomics to track the fate of 13C enriched substrates that vary in chemical composition as they are assimilated by microbes and transformed into new metabolic products in soil. We found that differences in forest nutrient economies (e.g., nutrient cycling, microbial competition) led to arbuscular mycorrhizal (AM) soils harboring greater diversity of fungi and bacteria than ectomycorrhizal (ECM) soils. When incubated with 13C enriched substrates, substrate type drove shifts in which species were active decomposers and the abundance of metabolic products that were reduced or saturated in the highly diverse AM soils. The decomposition pathways were more static in the less diverse, ECM soil. Importantly, the majority of these shifts were driven by taxa only present in the AM soil suggesting a strong link between microbial identity and their ability to decompose and assimilate substrates. Collectively, these results highlight an important interaction between ecosystem-level processes and microbial diversity; whereby the identity and function of active decomposers impacts the composition of decomposition products that can form stable SOM.

In silico screening of TMPRSS2 SNPs that affect its binding with SARS-CoV2 spike protein and directly involved in the interaction affinity changes

In this paper, we used in silico analysis to shed light on the possible interaction between TMPRSS2 and SARS-CoV2 spike (S) protein by examining the role of TMPRSS2 single nucleotide polymorphisms (SNPs) in relation with susceptibility and inter-individual variability of SARS-CoV2 infection. First, we used molecular docking of human TMPRSS2 protein to predict the binding site of TMPRSS2, especially the TMPRSS2 link loops, in order to assess the effect TMPRSS2 SNPs. The latter lead to missense variants on the interaction between TMPRSS2 and SARS-CoV2 S protein. In a second step, we further refine our analysis by performing a structure-function analysis of the complexes using PyMol software, and finally by MD simulations to validate the as-obtained results. Our findings show that 17 SNPs among the 692 natural TMPRSS2 coding variants are in positions to influence the binding of TMPRSS2 with the viral S protein. All of them give more important interaction energy as assessed by docking. Among the 17 SNPs, four missense variants E389A, K392Q, T393S and Q438E lead to "directly increasing" the interaction affinity and 2 missense variants R470I and Y416C cause it "directly decreasing". The R470I and Y416C present in African and American population, respectively. While the other 4 SNP variants (E389A; K392Q; T393S and Q438E) are present only in the European population, which could link the viral infection susceptibility to demographic, geographic and genetic factors.

Taxation and the Quality of Government

In this chapter we explore the connection between taxation and quality of government. Taxation represents an important interaction between citizens and the state, thus the way in which tax policies are organized has important implications for the quality of government. The first part of the chapter describes three different perspectives on quality of government: The first relates to administrative impartiality, the second to state size and economic growth, and the last to democracy. It then explores how each perspective holds distinct prescriptions for the design of tax policy. The latter part of the chapter applies the conclusions on the three perspectives to discuss exemplary cases of each over different historical periods. It concludes with a discussion of path dependence and the difficulty of maintaining a high quality of government in the long run.

Non-Symmetrical W-potential in Nonlinear Biophysics of Microtubules

In this work, we study nonlinear dynamics of microtubules. An important interaction among constitutive particles is modeled using W-potential. We compare a symmetric potential with two kinds of non-symmetric ones. An advantage of the latter ones is demonstrated.

Synthesis of 1-(2-Fluorophenyl)pyrazoles by 1,3-Dipolar Cycloaddition of the Corresponding Sydnones

3-Arylsydnones bearing fluorine and bromine atoms on the benzene ring were synthesized from N-nitroso-2-fluorophenylglycines and characterized by NMR spectroscopy. These were employed further in synthesis of the corresponding 1-(2-fluorophenyl)pyrazoles by 1,3-dipolar cycloaddition reaction with dimethyl acetylenedicarboxylate (DMAD) as activated dipolarophile. The sydnones as reaction intermediates were characterized by single crystal X-ray diffraction analysis showing interesting features such as halogen bonding as an important interaction in modeling the crystal structure.

POS1494-HPR THE COLLABORATION OF RHEUMATOLOGY-DERMATOLOGY IN THE EVALUATION OF RHEUMATIC DISEASES PATIENTS: EXPERIENCE IN A UNIVERSITY HOSPITAL

Background:Dermatological manifestations are not rare in patients with rheumatic diseases (RD). Multidisciplinary management and direct interaction between these disciplines are essential. According to Dermatology-Rheumatology clinics, most diagnoses evaluated are systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), with dermatitis being the most common manifestation. It is important to be aware that skin problems in RD patients are not always related to the underlying condition(1). Nowadays, there is significant evidence to support the manifold advantages of the joint dermatology-rheumatology clinics, including improved quality of care for patients and multidisciplinary training for new physicians(2). This ongoing trend is intended to highlight the important interaction between specialties that treat overlapping conditions, and it has been incorporated in academic health centers to give a comprehensive approach to patients.Objectives:Our purpose was to describe the collaboration between the Rheumatology and Dermatology services during the evaluation of RD patients.Methods:An observational, retrospective study was performed in the Rheumatology Service of the University Hospital “Dr. Jose Eleuterio Gonzalez” in Monterrey, Mexico, between March 2019 and February 2020. All the patients with a Rheumatology or Dermatology consultation requested were included (hospitalized and outpatients). Demographic (age, gender, baseline diagnosis), the reason for consultation, specialty requested, type of treatment, final diagnoses, and agreement in final diagnosis were registered. Results are shown in descriptive statistics.Results:One hundred and seventy-four patients were included, 142 (81.6%) patients from the outpatient clinic and 32 (18.4%) patients hospitalized. The mean age was 45.1 (SD±15.8) years, 135 (77.6%) were females, 54 (31%) patients were under initial diagnosis evaluation, 30 (17.2%) had RA, 25 (14.4%) patients had SLE, 15 (8.6%) patients had psoriatic arthritis, 12 (6.9%) patients had systemic sclerosis, 6 (3.4%) patients had dermatomyositis. The main reasons for consultation in hospitalized patients were acute lupus (15.6%), subacute lupus (12.5%), purpura (12.5%), cutaneous vasculitis (9.4%), urticarial dermatitis (9.4%), dermatomyositis (6.3%) and others (34.3%). The consultation requested was: 156 (89.7%) to Dermatology and 18 (10.3%) to Rheumatology. The type of treatment prescribed was topic/local in 37 (21.3%) patients, systemic in 25 (14.4%) and both in 92 (52.9%) patients. The final diagnoses were related to the underlying disease in 102 (77%) patients and unrelated in 40 (23%) patients. The agreement between initial clinical suspicion and final diagnoses reached 75.9% between Rheumatology and Dermatology services. Figure 1.Conclusion:The collaboration between Rheumatology and Dermatology services are very important. Most of the patients were under initial evaluation. All the rheumatologists and dermatologists should be aware of the interdependence from both specialties to give the best quality of care to the patients.References:[1]Samycia M, McCourt C, Shojania K, Au S. Experiences From a Combined Dermatology and Rheumatology Clinic: A Retrospective Review. J Cutan Med Surg. 2016;20(5):486-489. doi:10.1177/1203475416649138.[2]Theodorakopoulou E, Dalamaga M, Katsimbri P, Boumpas DT, Papadavid E. How does the joint dermatology-rheumatology clinic benefit both patients and dermatologists?. Dermatol Ther. 2020;33(3):e13283. doi:10.1111/dth.13283Figure 1.Disclosure of Interests:None declared

How to Manipulate Through-Space Conjugation and Clusterolumi-nescence of Simple AIEgens with Isolated Phenyl Rings?

<a>Apart from the traditional through-bond conjugation (TBC), through-space conjugation (TSC) is gradually proved as another important interaction in photophysical processes, especially for the recent observation of clusteroluminescence from nonconjugated molecules. </a>Herein, <a>simple and nonconjugated triphenylmethane (TPM) and its derivatives with electron-donating and electron-withdrawing groups were synthesized</a>, and their photophysical properties were systematically studied. <a>TPM was characterized with visible clusteroluminescence due to the intramolecular TSC. Experimental and theoretical results showed that the introduction of electron-donating groups into TPM could </a><a>red-shift </a>the wavelength and increase the efficiency of clusteroluminescence simultaneously, due to the increased electronic density and stabilization of TSC. However, TPM derivatives with electron-withdrawing groups showed inefficient or even quenched clusteroluminescence caused by the vigorous excited-state intramolecular motion and intermolecular photoinduced electron transfer process. This work provides a reliable strategy to manipulate TSC and clusteroluminescence.