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IN VITRO ANTIPLASMODIAL ACTIVITY OF NATIVE INDIAN SEAWEED SARGASSUM SP.

ABSTRACTObjectives: To investigate the antiplasmodial activity of three different solvent extracts of Sargassum tenerrimum against Plasmodium falciparum.Methods: The seaweed species of S. tenerrimum were collected from Rameshwaram, Southeast coast of India. The collected samples were dried andextracted with three different polaritic (hexane, acetone, and ethylacetate) solvents and tested against P. falciparum parasite strain.Results: Acetone extract exhibited better activity than the other two extracts. The inhibitory concentration values of acetone S. tenerrimum werefound to be 27.82 and 18.14 µg/ml at 24-48 hrs, respectively. S. tenerrimum crude extracts were subjected for the phytochemical analysis, and itshowed the presence of steroids, alkaloids, flavonoids, tannins, glycosides, amino acids, and phenol compounds. The gas chromatography-massspectroscopy result reveals that the presence of 10 major and minor compounds in the S. tenerrimum extract. In that, cyclotrisiloxane hexamethylcompounds might be responsible for the effective parasite suppression.50Conclusion: It can be concluded from the present study that the acetone extract of S. tenerrimum has strong antiplasmodial activity. Furthermore, thestudy has been extended to the isolation of the possible active compounds that is responsible for the antiplasmodial properties.Keywords: Antiplasmodial assay, Different polaritic solvents, Plasmodium falciparum, Sargassum tenerrimum

4′-Amino-2,2′′-dioxo-2,2′′,3,3′′-tetra­hydro-1H-indole-3-spiro-1′-cyclo­pent-3′-ene-2′-spiro-3′′-1H-indole-3′,5′,5′-tricarbonitrile dihydrate

In the title compound, C22H12N6O2·2H2O, the cyclo­pentene ring adopts an envelope conformation, with the spiro C atom bonded to the dicyano-substituted C atom deviating by 0.437 (2) Å from the plane of the remaining four atoms in the ring. The puckering and smallest displacement asymmetry parameters for the ring are q 2 = 0.275 (2) Å, ϕ = 212.4 (4)° and Δs(C2) = 2.7 (2). The dihedral angle between the two indole groups is 60.1 (1)°. The structure contains inter­molecular N—H⋯O hydrogen bonds involving the indole groups and O—H⋯O and O—H⋯N hydrogen bonds involving the water mol­ecules

CEP162 is an axoneme-recognition protein promoting ciliary transition zone assembly at the cilia base

The transition zone (TZ) is a specialized compartment found at the base of cilia, adjacent to the centriole distal end, where axonemal microtubules (MTs) are heavily cross-linked to the surrounding membrane to form a barrier that gates the ciliary compartment. A number of ciliopathy molecules have been found to associate with the TZ, but factors that directly recognize axonemal MTs to specify TZ assembly at the cilia base remain unclear. Here, through quantitative centrosome proteomics, we identified an axoneme-associated protein, CEP162, tethered specifically at centriole distal ends to promote TZ assembly. CEP162 interacts with core TZ components, and mediates their association with MTs. Loss of CEP162 arrests ciliogenesis at the stage of TZ assembly. Abolishing its centriolar tethering, however, allows CEP162 to stay on the growing end of the axoneme, and ectopically assemble TZ components at cilia tips. This generates extra-long cilia with strikingly swollen tips that actively release ciliary contents into the extracellular environment. CEP162 is thus an axoneme-recognition protein “pre-tethered” at centriole distal ends prior to ciliogenesis to promote and restrict TZ formation specifically at the cilia base

Genome wide association analysis of sorghum mini core lines regarding anthracnose, downy mildew, and head smut

In previous studies, a sorghum mini core collection was scored over several years for response to Colletotrichum sublineola, Peronosclerospora sorghi, and Sporisorium reilianum, the causal agents of the disease anthracnose, downy mildew, and head smut, respectively. The screening results were combined with over 290,000 Single nucleotide polymorphic (SNP) loci from an updated version of a publicly available genotype by sequencing (GBS) dataset available for the mini core collection. GAPIT (Genome Association and Prediction Integrated Tool) R package was used to identify chromosomal locations that differ in disease response. When the top scoring SNPs were mapped to the most recent version of the published sorghum genome, in each case, a nearby and most often the closest annotated gene has precedence for a role in host defense

Hsp90 governs dispersion and drug resistance of fungal biofilms

Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections

SERS-based detection of haptoglobin in ovarian cyst fluid as a point-of-care diagnostic assay for epithelial ovarian cancer

Purpose: To evaluate haptoglobin (Hp) in ovarian cyst fluid as a diagnostic biomarker for epithelial ovarian cancers (EOCs) using surface-enhanced Raman spectroscopy (SERS)-based in vitro diagnostic assay for use in an intraoperative setting. Methods: SERS-based method was used to detect and quantify Hp in archived ovarian cyst fluids collected from suspicious ovarian cysts and differentiate benign tumors from EOCs. The diagnostic performance of SERS-based assay was verified against the histopathology conclusions and compared with the results of CA125 test and frozen sections. Results: Hp concentration present in the clinical cyst fluid measured by SERS was normalized to 3.3 mg/mL of standard Hp. Normalized mean values for patients with benign cysts were 0.65 (n=57) and malignant cysts were 1.85 (n=54), demonstrating a significantly (P<0.01) higher Hp in malignant samples. Verified against histology, Hp measurements using SERS had a sensitivity of 94% and specificity of 91%. Receiver operating characteristic curve analysis of SERS-based Hp measurements resulted in area under the curve of 0.966±0.03, establishing the robustness of the method. CA125 test on the same set of patients had a sensitivity of 85% and specificity of 90%, while frozen section analysis on 65 samples had 100% sensitivity and specificity. Conclusion: With a total execution time of <10 minutes and consistent performance across different stages of cancer, the SERS-based Hp detection assay can serve as a promising intraoperative EOC diagnostic test.National Medical Research Council (NMRC), Singapore; Bio-Medical Research Council of Agency for Science, Technology and Research (A*STAR), and the NHIC Innovation to Develop (I2D

Comparison of distortion correction preprocessing pipelines for DTI in the upper limb

PURPOSE: DTI characterizes tissue microstructure and provides proxy measures of nerve health. Echo-planar imaging is a popular method of acquiring DTI but is susceptible to various artifacts (e.g., susceptibility, motion, and eddy currents), which may be ameliorated via preprocessing. There are many pipelines available but limited data comparing their performance, which provides the rationale for this study. METHODS: DTI was acquired from the upper limb of heathy volunteers at 3T in blip-up and blip-down directions. Data were independently corrected using (i) FSL's TOPUP & eddy, (ii) FSL's TOPUP, (iii) DSI Studio, and (iv) TORTOISE. DTI metrics were extracted from the median, radial, and ulnar nerves and compared (between pipelines) using mixed-effects linear regression. The geometric similarity of corrected b = 0 images and the slice matched T1-weighted (T1w) images were computed using the Sörenson-Dice coefficient. RESULTS: Without preprocessing, the similarity coefficient of the blip-up and blip-down datasets to the T1w was 0·80 and 0·79, respectively. Preprocessing improved the geometric similarity by 1% with no difference between pipelines. Compared to TOPUP & eddy, DSI Studio and TORTOISE generated 2% and 6% lower estimates of fractional anisotropy, and 6% and 13% higher estimates of radial diffusivity, respectively. Estimates of anisotropy from TOPUP & eddy versus TOPUP were not different but TOPUP reduced radial diffusivity by 3%. The agreement of DTI metrics between pipelines was poor. CONCLUSIONS: Preprocessing DTI from the upper limb improves geometric similarity but the choice of the pipeline introduces clinically important variability in diffusion parameter estimates from peripheral nerves

Emodin Suppresses Migration and Invasion through the Modulation of CXCR4 Expression in an Orthotopic Model of Human Hepatocellular Carcinoma

10.1371/journal.pone.0057015PLoS ONE83