Morphological, Metabolomic and Genomic Evidences on Drought Stress Protective Functioning of the Endophyte Bacillus safensis Ni7.

The metabolomic and genomic characterization of an endophytic Bacillus safensis Ni7 was carried out in this study. This strain has previously been isolated from the xerophytic plant Nerium indicum L. and reported to enhance the drought tolerance in Capsicum annuum L. seedlings. The effects of drought stress on the morphology, biofilm production, and metabolite production of B. safensis Ni7 are analyzed in the current study. From the results obtained, the organism was found to have multiple strategies such as aggregation and clumping, robust biofilm production, and increased production of surfactin homologues under the drought induced condition when compared to non-stressed condition. Further the whole genome sequencing (WGS) based analysis has demonstrated B. safensis Ni7 to have a genome size of 3,671,999 bp, N50 value of 3,527,239, and a mean G+C content of 41.58%. Interestingly the organism was observed to have the presence of various stress-responsive genes (13, 20U, 16U,160, 39, 17M, 18, 26, and ctc) and genes responsible for surfactin production (srfAA, srfAB, srfAC, and srfAD), biofilm production (epsD, epsE, epsF, epsG, epsH, epsI, epsK, epsL, epsM, epsN, and pel), chemotaxis (cheB_1, cheB_2, cheB_3, cheW_1, cheW_2 cheR, cheD, cheC, cheA, cheY, cheV, and cheB_4), flagella synthesis (flgG_1, flgG_2, flgG_3, flgC, and flgB) as supportive to the drought tolerance. Besides these, the genes responsible for plant growth promotion (PGP), including the genes for nitrogen (nasA, nasB, nasC, nasD, and nasE) and sulfur assimilation (cysL_1&L_2, cysI) and genes for phosphate solubilization (phoA, phoP_1& phoP_2, and phoR) could also be predicted. Along with the same, the genes for catalase, superoxide dismutase, protein homeostasis, cellular fitness, osmoprotectants production, and protein folding could also be predicted from its WGS data. Further pan-genome analysis with plant associated B. safensis strains available in the public databases revealed B. safensis Ni7 to have the presence of a total of 5391 gene clusters. Among these, 3207 genes were identified as core genes, 954 as shell genes and 1230 as cloud genes. This variation in gene content could be taken as an indication of evolution of strains of Bacillus safensis as per specific conditions and hence in the case of B. safensis Ni7 its role in habitat adaptation of plant is well expected. This diversity in endophytic bacterial genes may attribute its role to support the plant system to cope up with stress conditions. Overall, the study provides genomic evidence on Bacillus safensis Ni7 as a stress alleviating microbial partner in plants.

Femtomolar detection of SARS-CoV-2 via peptide beacons integrated on a miniaturized TIRF microscope.

The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) continues to pose a substantial global health threat. Along with vaccines and targeted therapeutics, there is a critical need for rapid diagnostic solutions. In this work, we use computational protein modeling tools to suggest molecular beacon architectures that function as conformational switches for high-sensitivity detection of the SARS-CoV-2 spike protein receptor binding domain (S-RBD). Integrating these beacons on a miniaturized total internal reflection fluorescence (mini-TIRF) microscope, we detect the S-RBD and pseudotyped SARS-CoV-2 with limits of detection in the femtomolar range. We envision that our designed mini-TIRF platform will serve as a robust platform for point-of-care diagnostics for SARS-CoV-2 and future emergent viral threats.

Epstein-Barr Virus Reactivation After Paediatric Haematopoietic Stem Cell Transplantation: Risk Factors and Sensitivity Analysis of Mathematical Model.

Epstein-Barr virus (EBV) establishes a lifelong latent infection in healthy humans, kept under immune control by cytotoxic T cells (CTLs). Following paediatric haematopoetic stem cell transplantation (HSCT), a loss of immune surveillance leads to opportunistic outgrowth of EBV-infected cells, resulting in EBV reactivation, which can ultimately progress to post-transplant lymphoproliferative disorder (PTLD). The aims of this study were to identify risk factors for EBV reactivation in children in the first 100 days post-HSCT and to assess the suitability of a previously reported mathematical model to mechanistically model EBV reactivation kinetics in this cohort. Retrospective electronic data were collected from 56 children who underwent HSCT at Great Ormond Street Hospital (GOSH) between 2005 and 2016. Using EBV viral load (VL) measurements from weekly quantitative PCR (qPCR) monitoring post-HSCT, a multivariable Cox proportional hazards (Cox-PH) model was developed to assess time to first EBV reactivation event in the first 100 days post-HSCT. Sensitivity analysis of a previously reported mathematical model was performed to identify key parameters affecting EBV VL. Cox-PH modelling revealed EBV seropositivity of the HSCT recipient and administration of anti-thymocyte globulin (ATG) pre-HSCT to be significantly associated with an increased risk of EBV reactivation in the first 100 days post-HSCT (adjusted hazard ratio (AHR) = 2.32, P = 0.02; AHR = 2.55, P = 0.04). Five parameters were found to affect EBV VL in sensitivity analysis of the previously reported mathematical model. In conclusion, we have assessed the effect of multiple covariates on EBV reactivation in the first 100 days post-HSCT in children and have identified key parameters in a previously reported mechanistic mathematical model that affect EBV VL. Future work will aim to fit this model to patient EBV VLs, develop the model to account for interindividual variability and model the effect of clinically relevant covariates such as rituximab therapy and ATG on EBV VL.

An Esterase with Increased Acetone Tolerance from Bacillus subtilis E9 over Expressed in E. coli BL21 Using pTac Bs-est Vector.

Bacillus subtilis E9 was identified as a potential strain producing esterase. The gene coding esterase from B. subtilis E9 was amplified using esterase-specific primers and the sequence was translated in silico. The presence of conserved catalytic triad amino acid residues (His-Ser-Asp/Glu) confirmed the functional nature of the esterase enzyme. Docking studies conducted with modeled protein and the ligand p-nitrophenyl acetate showed that the amino acid residues interacting with the ligand were Ser77, His76, and Gly103. The gene coding for esterase from B. subtilis E9 was cloned into an assembled vector having Tac promoter (pTac), pUC origin of replication, Ni-Histidine residues, ampicillin cassette, and T7 terminator using Golden gate DNA assembly method. The generated pTac Bs-est (4598 bp) recombinant plasmid was transformed and heterologously expressed in Escherichia coli BL21 (DE3) strain. The tagged recombinant protein was purified to yield 43.4% pure protein with specific activity of 772 U/mg. The purified recombinant protein was subjected to peptide sequencing and the identity was confirmed as esterase by peptide tandem mass fragmentation method using the LC-MS/MS analysis. The purified recombinant esterase was found to be organic solvent stable and tolerant up to 5 days retaining around 95% residual activity in 30-90% v/v Acetone. The recombinant esterase expressed in our study was found to exhibit better organic solvent stability and tolerance than compared to the original bacterial esterase from B. subtilis E9, a property which could be explored in the biocatalytic and synthetic transformation reactions for industrial applications.

Sub-Picomolar Detection of SARS-CoV-2 RBD via Computationally-Optimized Peptide Beacons

The novel coronavirus SARS-CoV-2 continues to pose a significant global health threat. Along with vaccines and targeted therapeutics, there is a critical need for rapid diagnostic solutions. In this work, we employ deep learning-based protein design to engineer molecular beacons that function as conformational switches for high sensitivity detection of the SARS-CoV-2 spike protein receptor binding domain (S-RBD). The beacons contain two peptides, together forming a heterodimer, and a binding ligand between them to detect the presence of S-RBD. In the absence of S-RBD (OFF), the peptide beacons adopt a closed conformation that opens when bound to the S-RBD and produces a fluorescence signal (ON), utilizing a fluorophore-quencher pair at the two ends of the heterodimer stems. Two candidate beacons, C17LC21 and C21LC21, can detect the S-RBD with limits of detection (LoD) in the sub-picomolar range. We envision that these beacons can be easily integrated with on-chip optical sensors to construct a point-of-care diagnostic platform for SARS-CoV-2.

Evaluation of facial and palatal alveolar bone thickness and sagittal root position of maxillary anterior teeth on cone beam computerized tomograms.

BACKGROUND: Amount of bone covering the facial and palatal surface of the root and the sagittal root position are important parameters while considering an immediate implant placement. AIMS: This study measures the distance from cement-enamel junction (CEJ) to alveolar crest and thickness of alveolar bone of maxillary anterior teeth facially and palatally at 5 different points. MATERIALS AND METHODS: CBCT scans of 79 systemically healthy patients were evaluated by two calibrated and independent examiners. Measurements like: 1) distance from CEJ to Crest. 2) Thickness of facial and palatal alveolar bone at five different points a) Crest, b) 2 mm from the crest, c) mid root level, d) apical 3rd, e) apex. 3) Sagittal root position. 4) Labiopalatal distance at the apex. 5) Length of the bone from apex to the nasal floor for incisors. 6) Presence of fenestrations and dehiscences were assessed. RESULTS: Healthy maxillary anteriors were evaluated and less than 2 mm bone was seen at all five points, 0.5 to 1 mm bone is seen in all anteriors at crest, 2 mm from crest, midroot, apical 3rd level. 1 to 2 mm is seen at apex. Labiopalatal width at apex ranged from 3 mm to 13 mm with a mean of 7.45 ± 2.24 mm for centrals, 7.69 ± 2.14 mm for lateral incisors, and 6.76 ± 2.42 mm for canines. CONCLUSION: The present study supports the finding of very thin facial bone over maxillary anteriors and frequent occurrence of fenestrations and dehiscences. Pre-treatment evaluation of alveolar bone surrounding the maxillary anteriors is important to avoid complications during implant placement.

Association of Serum Bilirubin with Acute Ischemic Stroke – An Observational Study

@#Introduction: Stroke is a common cause of mortality and morbidity and has an increasing prevalence across the world.1 Bilirubin is now being considered an antioxidant which increases in response to diseases associated with increased oxidative stress. Hence the present observational study was undertaken to assess the bilirubin levels with the outcome of acute ischemic stroke. Methods: This observational study was conducted from January 2018 to December 2018 on 64 ischemic stroke patients admitted at KLE’S Dr. Prabhakar kore hospital at Belagavi, Karnataka. All adult patients above 18 years of age presenting with cerebrovascular accident and proved as ischemic stroke on CT scan or MRI scan were included. The patients were empirically divided into different Groups based on the bilirubin level. They were then analysed with their NIHSS scores for assessing stroke severity. Results: A total of 64 patients were included in the final analysis. The mean total bilirubin level in the patients was 0.68±0.34 mg/dl ( mean±SD). 34.3% (22) of ischemic stroke patients in the study had serum total bilirubin levels 0.7 mg/dl or more. Mean NIHSS Score for Group 1(Low) total bilirubin group was 9.37 and for Group 2(High) bilirubin group was 10.9, which was statistically not significant. This indicates that there was no significant correlation between total bilirubin and severity of symptoms at the time of admission.There was no statistically significant correlation between NIHSS and direct bilirubin levels Conclusion: The current study has documented no association between the bilirubin levels and stroke severity and prognosis.

Nearest-neighbor NMR spectroscopy: categorizing spectral peaks by their adjacent nuclei.

Methyl-NMR enables atomic-resolution studies of structure and dynamics of large proteins in solution. However, resonance assignment remains challenging. The problem is to combine existing structural informational with sparse distance restraints and search for the most compatible assignment among the permutations. Prior classification of peaks as either from isoleucine, leucine, or valine reduces the search space by many orders of magnitude. However, this is hindered by overlapped leucine and valine frequencies. In contrast, the nearest-neighbor nuclei, coupled to the methyl carbons, resonate in distinct frequency bands. Here, we develop a framework to imprint additional information about passively coupled resonances onto the observed peaks. This depends on simultaneously orchestrating closely spaced bands of resonances along different magnetization trajectories, using principles from control theory. For methyl-NMR, the method is implemented as a modification to the standard fingerprint spectrum (the 2D-HMQC). The amino acid type is immediately apparent in the fingerprint spectrum. There is no additional relaxation loss or an increase in experimental time. The method is validated on biologically relevant proteins. The idea of generating new spectral information using passive, adjacent resonances is applicable to other contexts in NMR spectroscopy.

Effect of prophylactic or therapeutic administration of paracetamol on immune response to DTwP-HepB-Hib combination vaccine in Indian infants.

BACKGROUND: Vaccination is considered as the most cost effective method for preventing infectious diseases. Low grade fever is a known adverse effect of vaccination. In India, it is a common clinical practice to prescribe paracetamol either prophylactically or therapeutically to manage fever. Some studies have shown that paracetamol interferes with antibody responses following immunization. This manuscript reports the outcome of a post hoc analysis of data from a clinical trial of a pentavalent vaccine in Indian infants where paracetamol was not used or was used either as prophylaxis or for treatment of fever. METHODS: Pre and post vaccine antibody levels against Diphtheria, Tetanus, Pertussis, Hepatitis B, Haemophilus influenzae type B were assessed in no paracetamol and paracetamol groups. The paracetamol group was further divided into prophylactic and treatment groups. RESULTS: Similar rates of seroprotection/seroresponse for anti-D, anti-T, anti-wP, anti-PT, anti-HBs and anti-PRP were observed in all the groups. There was no clear tendency for difference in percentage seroprotection/seroresponse and geometric mean (GM) titers in any of the groups. CONCLUSION: The study found no evidence that paracetamol usage either as prophylactic or for treatment impact immunological responses to DTwP-HepB-Hib combination vaccine. [Clinical trial registry of India (study registration number CTRI/2012/08/002872)].

Optimization of laccase production from Marasmiellus palmivorus LA1 by Taguchi method of Design of experiments.

BACKGROUND: Fungal laccase has profound applications in different fields of biotechnology due to its broad specificity and high redox potential. Any successful application of the enzyme requires large scale production. As laccase production is highly dependent on medium components and cultural conditions, optimization of the same is essential for efficient product production. RESULTS: Production of laccase by fungal strain Marasmiellus palmivorus LA1 under solid state fermentation was optimized by the Taguchi design of experiments (DOE) methodology. An orthogonal array (L8) was designed using Qualitek-4 software to study the interactions and relative influence of the seven selected factors by one factor at a time approach. The optimum condition formulated was temperature (28 °C), pH (5), galactose (0.8%w/v), cupric sulphate (3 mM), inoculum concentration (number of mycelial agar pieces) (6Nos.) and substrate length (0.05 m). Overall yield increase of 17.6 fold was obtained after optimization. Statistical optimization leads to the elimination of an insignificant medium component ammonium dihydrogen phosphate from the process and contributes to a 1.06 fold increase in enzyme production. A final production of 667.4 ± 13 IU/mL laccase activity paves way for the application of this strain for industrial applications. CONCLUSION: Study optimized lignin degrading laccases from Marasmiellus palmivorus LA1. This laccases can thus be used for further applications in different scales of production after analyzing the properties of the enzyme. Study also confirmed the use of taguchi method for optimizations of product production.

Disability and Quality of Life of Subjects with Bipolar Affective Disorder in Remission.

BACKGROUND: Despite significant advances in pharmacological and psychological therapies for bipolar disorder, many people continue to have less than optimal outcomes, which are associated with significant disability and poor quality of life (QOL). This study aimed to assess the disability and QOL and factors associated with such suboptimal outcomes in subjects with bipolar disorder in remission. METHODS: Consecutive patients diagnosed to have bipolar disorder in remission attending the Department of Psychiatry, MOSC Medical College, Kerala, India were recruited for the study. They were assessed using the International Classification of Diseases Diagnostic Criteria for Research-10, Hamilton Scale for Depression, Young's Mania Rating Scale, World Health Organization-QOL (WHO QOL-BREF), WHO-Disability Assessment Scale (WHO-DAS), and Kuppuswamy's scale for socioeconomic status assessment. RESULTS: Eighty-four patients were evaluated. The mean total WHO-DAS score was 19.2 ± 2.09, the maximum disability in domain 4 (getting along) followed by domain 2 (mobility). The mean total WHO-QOL BREF score was 54.26 ± 2.85, the lowest subscore in domain 3 (social interactions). Disability scores were significantly associated with increasing age, female gender, not being an earning member of the family, and lower QOL scores. Poorer QOL scores were significantly associated with increasing age and higher disability score. CONCLUSIONS: Many bipolar patients in remission have significant disability and poorer QOL. There is a need for longitudinal studies to explore such associations and develop interventions to reduce the disability thereby enhancing the QOL.

Expression of Mx Gene in Cirrhinus mrigala (Hamilton, 1822) to OmpC Protein of Aeromonas hydrophila and Bacterial Infection.

The aims of this study were to identify alternative myxovirus (Mx) stimulatory compounds in Cirrhinus mrigala and to characterize the kinetics and intensity of their stimulated responses by semi-quantitative RT-PCR. Mx transcripts were measured in C. mrigala injected with Aeromonas OmpC (outer membrane protein) at a dose 0.4 mg/fish. At day 1, day 2, day 3, day 5, day 10, day 20 and day 30, samples were collected from kidney, spleen, liver, heart brain, gill, intestine and muscle for the study of Mx transcript and housekeeping gene ß-actin. Similarly, Mx gene expression was also studied in Aeromonas hydrophila-infected fish for a period of 10 days. Mx/ß-actin ratio was constitutively expressed from all the organs of OmpC-vaccinated fish. The expression was significantly highest (P ≤ 0.05) in spleen, followed by liver, kidney, intestine, gill, heart, muscle and brain. The expression was highest in day 2 except spleen (on day 3) and subsequently reduced up to day 30. Control fish also showed Mx expression. Similarly, A. hydrophila-infected fish showed Mx/ß-actin ratio upregulated significantly in the spleen and kidney on day 5, liver on day 2 and intestine on day 3. This study revealed that OmpC of A. hydrophila and its infection could stimulate the antiviral Mx gene of C. mrigala.

Electrochemical Performance of Electrophoretically Deposited Nanostructured LiMnPO4-Sucrose Derived Carbon Composite Electrodes for Lithium Ion Batteries.

The present study reports an approach by which thin films of sucrose added olivine type LiMnPO4-Ccomposite and pristine LiMnPO4 is made by a technique of electrophoretic co-deposition in which pristine and composite samples were synthesized by a sol-gel route. These thin films with enhanced surface area is used to fabricate cathodes for rechargeable Li ion batteries. XRD confirms phase pure single crystalline orthorhombic structure. Transmission Electron Microscopy (TEM) images shows the carbon coating over LiMnPO4 and the particle size restricted in the nano regime. The presence of sp2 hybridized carbon on LiMnPO4 particles is confirmed by X-ray Photon spectroscopy (XPS). To explore the electrochemical behavior, cyclic voltammetry (CV) and cycling studies were performed. The specific capacity for LiMnPO4-C is found to be increased by 43% in comparison to the pristine LiMnPO4. It also exhibited 86% retention in capacity compared to the pristine LiMnPO4 (52%). The result indicates that a proper carbon coating can significantly improve the electronic conductivity and hence the specific capacity.

Identification of chemical compounds present in different fractions of Annona reticulata L. leaf by using GC-MS.

GC-MS analysis of fractions prepared from hydro-alcoholic extract of Annona reticulata Linn (Family Annonaceae) leaf revealed the presence of 9,10-dimethyltricyclo[4.2.1.1(2,5)]decane-9,10-diol; 4-(1,5-dihydroxy-2,6,6-trimethylcyclohex-2-enyl)but-3-en-2-one; 3,7-dimethyl-6-nonen-1-ol acetate; 9-octadecenamide,(Z)-; glycerine; D-glucose,6-O-α-D-galactopyranosyl-; desulphosinigrin and α-methyl-D-mannopyranoside as few of the major compounds in different fractions. The presence of these compounds in the plant has been identified for the first time.

Identification of reproduction-related genes and SSR-markers through expressed sequence tags analysis of a monsoon breeding carp rohu, Labeo rohita (Hamilton).

Labeo rohita (Ham.) also called rohu is the most important freshwater aquaculture species on the Indian sub continent. Monsoon dependent breeding restricts its seed production beyond season indicating a strong genetic control about which very limited information is available. Additionally, few genomic resources are publicly available for this species. Here we sought to identify reproduction-relevant genes from normalized cDNA libraries of the brain-pituitary-gonad-liver (BPGL-axis) tissues of adult L. rohita collected during post preparatory phase. 6161 random clones sequenced (Sanger-based) from these libraries produced 4642 (75.34%) high-quality sequences. They were assembled into 3631 (78.22%) unique sequences composed of 709 contigs and 2922 singletons. A total of 182 unique sequences were found to be associated with reproduction-related genes, mainly under the GO term categories of reproduction, neuro-peptide hormone activity, hormone and receptor binding, receptor activity, signal transduction, embryonic development, cell-cell signaling, cell death and anti-apoptosis process. Several important reproduction-related genes reported here for the first time in L. rohita are zona pellucida sperm-binding protein 3, aquaporin-12, spermine oxidase, sperm associated antigen 7, testis expressed 261, progesterone receptor membrane component, Neuropeptide Y and Pro-opiomelanocortin. Quantitative RT-PCR-based analyses of 8 known and 8 unknown transcripts during preparatory and post-spawning phase showed increased expression level of most of the transcripts during preparatory phase (except Neuropeptide Y) in comparison to post-spawning phase indicating possible roles in initiation of gonad maturation. Expression of unknown transcripts was also found in prolific breeder common carp and tilapia, but levels of expression were much higher in seasonal breeder rohu. 3631 unique sequences contained 236 (6.49%) putative microsatellites with the AG (28.16%) repeat as the most frequent motif. Twenty loci showed polymorphism in 36 unrelated individuals with allele frequency ranging from 2 to 7 per locus. The observed heterozygosity ranged from 0.096 to 0.774 whereas the expected heterozygosity ranged from 0.109 to 0.801. Identification of 182 important reproduction-related genes and expression pattern of 16 transcripts in preparatory and post-spawning phase along with 20 polymorphic EST-SSRs should be highly useful for the future reproductive molecular studies and selection program in Labeo rohita.

Identification of anabolic selective androgen receptor modulators with reduced activities in reproductive tissues and sebaceous glands.

Androgen replacement therapy is a promising strategy for the treatment of frailty; however, androgens pose risks for unwanted effects including virilization and hypertrophy of reproductive organs. Selective Androgen Receptor Modulators (SARMs) retain the anabolic properties of androgens in bone and muscle while having reduced effects in other tissues. We describe two structurally similar 4-aza-steroidal androgen receptor (AR) ligands, Cl-4AS-1, a full agonist, and TFM-4AS-1, which is a SARM. TFM-4AS-1 is a potent AR ligand (IC(50), 38 nm) that partially activates an AR-dependent MMTV promoter (55% of maximal response) while antagonizing the N-terminal/C-terminal interaction within AR that is required for full receptor activation. Microarray analyses of MDA-MB-453 cells show that whereas Cl-4AS-1 behaves like 5alpha-dihydrotestosterone (DHT), TFM-4AS-1 acts as a gene-selective agonist, inducing some genes as effectively as DHT and others to a lesser extent or not at all. This gene-selective agonism manifests as tissue-selectivity: in ovariectomized rats, Cl-4AS-1 mimics DHT while TFM-4AS-1 promotes the accrual of bone and muscle mass while having reduced effects on reproductive organs and sebaceous glands. Moreover, TFM-4AS-1 does not promote prostate growth and antagonizes DHT in seminal vesicles. To confirm that the biochemical properties of TFM-4AS-1 confer tissue selectivity, we identified a structurally unrelated compound, FTBU-1, with partial agonist activity coupled with antagonism of the N-terminal/C-terminal interaction and found that it also behaves as a SARM. TFM-4AS-1 and FTBU-1 represent two new classes of SARMs and will allow for comparative studies aimed at understanding the biophysical and physiological basis of tissue-selective effects of nuclear receptor ligands.

Manifestation of helical edge states as zero bias magneto-tunneling-conductance peaks in noncentrosymmetric superconductors.

Helical edge states exist in the mixed spin singlet and triplet phase of a noncentrosymmetric superconductor (NCSS) when the pair amplitude (PA) in the negative helicity band, Δ(-), is smaller than the PA in the positive helicity band, Δ(+), i.e., when the PA in the triplet component is more than the same in the singlet component. We numerically determine energies of these edge states as a function of γ = Δ(-)/Δ(+). The presence of these edge states is reflected in the tunneling process from a normal metal to an NCSS across a bias energy eV. (i) Angle resolved spin conductance (SC) obeying the symmetry g(s)(φ) = -g(s)(-φ) shows peaks when the bias energy equals the available quasiparticle edge state energy provided [Formula: see text]. (ii) The total SC, G(s), is zero but modulates with eV for finite magnetic field H. (iii) The zero bias peaks of G(s) and total charge conductance, G(c), at finite H split into two at finite eV for moderate H. (iv) At zero bias, G(c) and G(s) increase with H and show peaks at |H|∼γH(0), where H(0) is a characteristic field.

Aqua-{6,6'-dimeth-oxy-2,2'-[ethane-1,2-diylbis(nitrilo-methyl-idyne)]diphenolato}(4-hydroxy-benzoato)manganese(III).

The title compound, [Mn(C(18)H(18)N(2)O(4))(C(7)H(5)O(3))(H(2)O)], was synthesized by a template reaction of ethane-1,2-diamine and 3-methoxy-salicylaldehyde in presence of manganese(II) 4-hydroxy-benzoate. The Jahn-Teller-distorted manganese(III) centre has an octa-hedral geometry. Extensive O-H⋯O hydrogen-bonding inter-actions generate a two-dimensional sheet structure parallel to (103).

Design and synthesis of potent and subtype-selective PPARalpha agonists.

Beginning with a moderately potent PPARgamma agonist 9, a series of potent and highly subtype-selective PPARalpha agonists was identified through a systematic SAR study. Based on the results of the efficacy studies in the hamster and dog models of dyslipidemia and the desired pharmacokinetic data, the optimized compound 39 was selected for further profiling.

Novel 2,3-dihydrobenzofuran-2-carboxylic acids: highly potent and subtype-selective PPARalpha agonists with potent hypolipidemic activity.

The design and synthesis of a novel class of 2,3-dihydrobenzofuran-2-carboxylic acids as highly potent and subtype-selective PPARalpha agonists are reported. Systematic study of structure-activity relationships has identified several key structural elements within this class for maintaining the potency and subtype selectivity. Select compounds were evaluated in animal models of dyslipidemia using Syrian hamsters and male Beagle dogs, and all these compounds displayed excellent cholesterol- and triglyceride-lowering activity at dose levels that were much lower than the marketed weak PPARalpha agonist fenofibrate.