C(4)-alkyl substituted furanyl cyclobutenediones as potent, orally bioavailable CXCR2 and CXCR1 receptor antagonists

A novel series of cyclobutenedione centered C(4)-alkyl substituted furanyl analogs was developed as potent CXCR2 and CXCR1 antagonists. Compound 16 exhibits potent inhibitory activities against IL-8 binding to the receptors (CXCR2 Ki=1 nM, IC(50)=1.3 nM; CXCR1 Ki=3 nM, IC(50)=7.3 nM), and demonstrates potent inhibition against both Gro-alpha and IL-8 induced hPMN migration (chemotaxis: CXCR2 IC(50)=0.5 nM, CXCR1 IC(50)=37 nM). In addition, 16 has shown good oral pharmacokinetic profiles in rat, mouse, monkey, and dog.     

Steroidal C-21 heteroaryl thioethers (Part 2): discovery of orally bioavailable selective glucocorticoid receptor modulators (dissociated steroids)

The prednisolone C-21 heteroaryl thioethers have been synthesized and evaluated in cell based transrepression and transactivation assays. Most of the compounds demonstrated weak transactivational activity in both human and rat tyrosineaminotransferase functional assay while keeping potent anti-inflammatory activity. The benzimidazole thioether 7 exhibited comparable anti-inflammatory activity and improved safety profile compared to the classical oral steroid prednisolone.     

A standard set of polymorphic microsatellites for threatened mountain ungulates (Caprini,Artiodactyla)

Nearly 70% of the world's mountain ungulate taxa are endangered. The availability of a standard set of DNA markers for forensic and molecular ecology studies would help to establish conservation programs and detect poaching activities of these endangered taxa. We tested 60 published microsatellite primer pairs from bovids (cattle, sheep and goat) on 49 individuals from 11 taxa including six wild goat‐like species (Capra spp.), three divergent wild sheep (Ovis spp.), and two chamois (Rupicapra spp.) species. Approximately 30 microsatellites amplified a microsatellite‐like PCR product in all three genera, and with the exception of ILST097, nearly all the loci were polymorphic within most of the 11 species.     

Complete chloroplast genome of the medicinal plant Evolvulus alsinoides: comparative analysis,identification of mutational hotspots and evolutionary dynamics with species of Solanales

Evolvulus alsinoides, belonging to the family Convolvulaceae, is an important medicinal plant widely used as a nootropic in the Indian traditional medicine system. In the genus Evolvulus, no research on the chloroplast genome has been published. Hence, the present study focuses on annotation, characterization, identification of mutational hotspots, and phylogenetic analysis in the complete chloroplast genome (cp) of E. alsinoides. Genome comparison and evolutionary dynamics were performed with the species of Solanales. The cp genome has 114 genes (80 protein-coding genes, 30 transfer RNA, and 4 ribosomal RNA genes) that were unique with total genome size of 157,015 bp. The cp genome possesses 69 RNA editing sites and 44 simple sequence repeats (SSRs). Predicted SSRs were randomly selected and validated experimentally. Six divergent hotspots such as trnQ-UUG, trnF-GAA, psaI, clpP, ndhF, and ycf1 were discovered from the cp genome. These microsatellites and divergent hot spot sequences of the Taxa ‘Evolvulus’ could be employed as molecular markers for species identification and genetic divergence investigations. The LSC area was found to be more conserved than the SSC and IR region in genome comparison. The IR contraction and expansion studies show that nine genes rpl2, rpl23, ycf1, ycf2, ycf1, ndhF, ndhA, matK, and psbK were present in the IR-LSC and IR-SSC boundaries of the cp genome. Fifty-four protein-coding genes in the cp genome were under negative selection pressure, indicating that they were well conserved and were undergoing purifying selection. The phylogenetic analysis reveals that E. alsinoides is closely related to the genus Cressa with some divergence from the genus Ipomoea. This is the first time the chloroplast genome of the genus Evolvulus has been published. The findings of the present study and chloroplast genome data could be a valuable resource for future studies in population genetics, genetic diversity, and evolutionary relationship of the family Convolvulaceae.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12298-021-01051-w.     

Structure, magnetic properties, catalase activity and DFT studies of [Mn2(μ-RCOO)2(μ-OR)2] type dinuclear manganese(III,III) complexes

Three Mn(III,III) complexes containing dibenzoylmethane (dbm), Mn₂(OMe)₂(dbm)₂(ClH₂CCOO)₂ (1), Mn₂(OMe)₂(dbm)₂(Cl₂HCCOO)₂ (2) and Mn₂(OMe)₂(dbm)₂(Cl₃CCOO)₂ (3) were synthesized. Crystal structure determination and magnetic characterization were done for 2. The Mn?Mn distance in complex 2 is 2.865 Å. It exhibits antiferromagnetic coupling with exchange parameter |J| = 20.4 cm⁻¹ (H = −2JS_AS_B). All three complexes, though insoluble in common solvents, catalyse the disproportionation of hydrogen peroxide when dispersed on silica gel with turnover numbers ∼150-300. DFT simulations showed that bridging moieties have remarkable effect on intermetallic distances in dimanganese(III,III) complexes.     

Comparison of Glucose and Lipid Metabolic Gene Expressions between Fat and Lean Lines of Rainbow Trout after a Glucose Load

Two experimental rainbow trout lines developed through divergent selection for low (Lean ‘L’ line) or high (Fat ‘F’ line) muscle fat content were used as models to study the genetic determinism of fat depots. Previous nutritional studies suggested that the F line had a better capability to use glucose than the L line during feeding trials. Based on that, we put forward the hypothesis that F line has a greater metabolic ability to clear a glucose load effectively, compared to L line. In order to test this hypothesis, 250 mg/kg glucose was intraperitoneally injected to the two rainbow trout lines fasted for 48 h. Hyperglycemia was observed after glucose treatment in both lines without affecting the phosphorylation of AMPK (cellular energy sensor) and Akt-TOR (insulin signaling) components. Liver glucokinase and glucose-6-phosphate dehydrogenase expression levels were increased by glucose, whereas mRNA levels of β-oxidation enzymes (CPT1a, CPT1b, HOAD and ACO) were down-regulated in the white skeletal muscle of both lines. Regarding the genotype effect, concordant with normoglycemia at 12 h after glucose treatment, higher muscle glycogen was found in F line compared to L line which exhibited hyperglycemia. Moreover, mRNA levels of hepatic glycolytic enzymes (GK, 6PFK and PK), gluconeogenic enzyme PEPCK and muscle fatty acid oxidation enzymes (CPT1a, CPT1b and HOAD) were concurrently higher in the F line. Overall, these findings suggest that F line may have a better ability to maintain glucose homeostasis than L line.     

Spectroscopic and photoluminescence characterization of Dy3+ in Sr0.5Ca0.5TiO3 phosphor

The spectroscopic and photoluminescence characteristics of trivalent dysprosium (Dy³⁺)‐doped Sr_0.5Ca_0.5TiO₃ phosphor materials synthesized via solid‐state reaction method were studied. The X‐ray diffraction profile confirmed the orthorhombic perovskite structure of the prepared samples. Judd–Ofelt analysis was carried out to obtain the intensity parameters and predicted radiative properties of Sr_0.5Ca_0.5TiO₃:2wt%Dy³⁺. The photoluminescence spectrum of Dy³⁺‐doped Sr_0.5Ca_0.5TiO₃ showed three emission peaks at 481, 574 and 638 nm corresponding to ⁴F_9/2→⁶H_15/2, ⁴F_9/2→⁶H_13/2 and ⁴F_9/2→⁶H_11/2 transitions respectively. The variation of luminescence intensity with different excitation wavelengths and Dy³⁺ concentrations is discussed. The decay profiles of ⁴F_9/2 excited levels of Dy³⁺ ions show bi‐exponential behaviour and also a decrease in average lifetime with increase in Dy³⁺ concentration. Yellow to blue luminescence intensity ratio, CIE chromaticity co‐ordinates and correlated color temperature were also calculated for different concentrations of Dy³⁺‐doped Sr_0.5Ca_0.5TiO₃ phosphor at different λ_ex. Copyright © 2015 John Wiley & Sons, Ltd.     

Toad radiation reveals into-India dispersal as a source of endemism in the Western Ghats-Sri Lanka biodiversity hotspot

Background  

High taxonomic level endemism in the Western Ghats-Sri Lanka biodiversity hotspot has been typically attributed to the subcontinent's geological history of long-term isolation. Subsequent out of – and into India dispersal of species after accretion to the Eurasian mainland is therefore often seen as a biogeographic factor that 'diluted' the composition of previously isolated Indian biota. However, few molecular studies have focussed on into-India dispersal as a possible source of endemism on the subcontinent. Using c. 6000 base pairs of mitochondrial and nuclear DNA, we investigated the evolutionary history and biogeography of true toads (Bufonidae), a group that colonized the Indian Subcontinent after the Indo-Asia collision.