Bioactive secondary metabolites from new endophytic fungus Curvularia. sp isolated from Rauwolfia macrophylla.

Kaaniche F, Hamed A, Abdel-Razek AS, et al. Bioactive secondary metabolites from new endophytic fungus Curvularia. sp isolated from Rauwolfia macrophylla. PLoS ONE. 2019;14(6): E0217627.Over the last decades, endophytic fungi represent a new source of pharmacologically active secondary metabolites based on the underlying assumption that they live symbiotically within their plant host. In the present study, a new endophytic fungus was isolated from Rauwolfia macrophylla, a medicinal plant from Cameroon. The fungus showed a highest homology to Curvularia sp. based on complete nucleotide sequence data generated from the internal transcribed spacer (ITS) of ribosomal DNA region. Large scale fermentation, working-up and separation of the strain extract using different chromatographic techniques afforded three bioactive compounds: 2'-deoxyribolactone (1), hexylitaconic acid (2) and ergosterol (3). The chemical structures of compounds 1-3 were confirmed by 1 and 2D NMR spectroscopy and mass spectrometry, and comparison with corresponding literature data. Biologically, the antimicrobial, antioxidant activities and the acetylcholinesterase inhibitory of the isolated compounds were studied

Cystatin C: A Candidate Biomarker for Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurologic disease characterized by progressive motor neuron degeneration. Clinical disease management is hindered by both a lengthy diagnostic process and the absence of effective treatments. Reliable panels of diagnostic, surrogate, and prognostic biomarkers are needed to accelerate disease diagnosis and expedite drug development. The cysteine protease inhibitor cystatin C has recently gained interest as a candidate diagnostic biomarker for ALS, but further studies are required to fully characterize its biomarker utility. We used quantitative enzyme-linked immunosorbent assay (ELISA) to assess initial and longitudinal cerebrospinal fluid (CSF) and plasma cystatin C levels in 104 ALS patients and controls. Cystatin C levels in ALS patients were significantly elevated in plasma and reduced in CSF compared to healthy controls, but did not differ significantly from neurologic disease controls. In addition, the direction of longitudinal change in CSF cystatin C levels correlated to the rate of ALS disease progression, and initial CSF cystatin C levels were predictive of patient survival, suggesting that cystatin C may function as a surrogate marker of disease progression and survival. These data verify prior results for reduced cystatin C levels in the CSF of ALS patients, identify increased cystatin C levels in the plasma of ALS patients, and reveal correlations between CSF cystatin C levels to both ALS disease progression and patient survival

Computer-Assisted Classification Patterns in Autoimmune Diagnostics: The AIDA Project

Antinuclear antibodies (ANAs) are significant biomarkers in the diagnosis of autoimmune diseases in humans, done by mean of Indirect ImmunoFluorescence (IIF)method, and performed by analyzing patterns and fluorescence intensity. This paper introduces the AIDA Project (autoimmunity: diagnosis assisted by computer) developed in the framework of an Italy-Tunisia cross-border cooperation and its preliminary results. A database of interpreted IIF images is being collected through the exchange of images and double reporting and a Gold Standard database, containing around 1000 double reported images, has been settled. The Gold Standard database is used for optimization of aCAD(Computer AidedDetection) solution and for the assessment of its added value, in order to be applied along with an Immunologist as a second Reader in detection of autoantibodies. This CAD system is able to identify on IIF images the fluorescence intensity and the fluorescence pattern. Preliminary results show that CAD, used as second Reader, appeared to perform better than Junior Immunologists and hence may significantly improve their efficacy; compared with two Junior Immunologists, the CAD system showed higher Intensity Accuracy (85,5% versus 66,0% and 66,0%), higher Patterns Accuracy (79,3% versus 48,0% and 66,2%), and higher Mean Class Accuracy (79,4% versus 56,7% and 64.2%)

Unraveling the performance of dispersion-corrected functionals for the accurate description of weakly bound natural polyphenols

Long-range non-covalent interactions play a key role in the chemistry of natural polyphenols. We have previously proposed a description of supramolecular polyphenol complexes by the B3P86 density functional coupled with some corrections for dispersion. We couple here the B3P86 functional with the D3 correction for dispersion, assessing systematically the accuracy of the new B3P86-D3 model using for that the well-known S66, HB23, NCCE31, and S12L datasets for non-covalent interactions. Furthermore, the association energies of these complexes were carefully compared to those obtained by other dispersion-corrected functionals, such as B(3)LYP-D3, BP86-D3 or B3P86-NL. Finally, this set of models were also applied to a database composed of seven non-covalent polyphenol complexes of the most interest.FDM acknowledges financial support from the Swedish Research Council (Grant No. 621-2014-4646) and SNIC (Swedish National Infrastructure for Computing) for providing computer resources. The work in Limoges (IB and PT) is supported by the “Conseil Régional du Limousin”. PT gratefully acknowledges the support by the Operational Program Research and Development Fund (project CZ.1.05/2.1.00/03.0058 of the Ministry of Education, Youth and Sports of the Czech Republic). IB gratefully acknowledges financial support from “Association Djerbienne en France”

Does BMI Really Alter the Hormonal Profile in Infertile Women? Retrospective Study in the Region of Sidi Bel Abbes (West Algeria)

Background: In last few years .; it’s  increasingly being recognized  that  Reproductive function is controlled by the hypothalamic–pituitary– gonadal axis, which is regulated by numerous endogenous and environmental factors  such us adipose accumulation in obesity  contributing to reproductive failure  such as menstrual disorders and infertility, gestational failure and obstetric complications, and infertility , Distinct changes in circulating sex hormones appear to underline these abnormalities. The objective: The aim of this study was to elucidate the possible correlation between body mass index as fatness indicator and hormonal profile in infertile women from the west of Algeria. To identify the impact of overweight  and obesity on female hormonal profile ; we  conducted a prospective study  measuring pituitary hormones  (FSH  and LH and prolactin ) , steroid sex hormones ( progesterone , testosterone and estradiol ) , anti miulleian hormone , and thyroidal hormones (FT3 , FT4 and TSH) in 360 women  consulting for subfertility in private genecologycal and obstetrical centers in SID BELABESS (West of Algeria ) Result: Our study showed that the majority of patients were aged between 20 and 29 years, representing a percentage of 47.8%, with the average age in sample (31.65 ± 6,93ans). The majority of subjects was obese   46.4%, or overweight (39.4%) with an average BMI of (29.76 ± 4,85Kg / m2). No statistically significant association was found between the BMI as obesity indicator with hormonal levels of pituitary hormones  (FSH  and LH and prolactin ) , steroid sex hormones ( progesterone , testosterone and estradiol ) , anti miulleian hormone , and thyroidal hormones (FT3 , FT4 and TSH). A negative and statistically significant correlation between the age of the patients and the AMH level (R = -0.60, P <0.01) was noted. Conclusion: The results of our study showed that the majority of women included in our study had a high BMI but no statistical significant difference was found between underweight , normal , overweight and obese women , that’s why more studies should be conducted to elucidate the in which level does obesity impair the reproductive outcomes. Keywords: Female infertility, hormonal profile, BMI, SBA, Algeria

Covalent Organic Framework (C6N6) as a Drug Delivery Platform for Fluorouracil to Treat Cancerous Cells: A DFT Study

Continuous studies are being carried out to explore new methods and carrier surfaces for target drug delivery. Herein, we report the covalent triazine framework C6N6 as a drug delivery carrier for fluorouracil (FU) and nitrosourea (NU) anti-cancer drugs. FU and NU are physiosorbed on C6N6 with adsorption energies of −28.14 kcal/mol and −27.54 kcal/mol, respectively. The outcomes of the non-covalent index (NCI) and quantum theory of atoms in molecules (QTAIM) analyses reveal that the FU@C6N6 and NU@C6N6 complexes were stabilized through van der Waals interactions. Natural bond order (NBO) and electron density difference (EDD) analyses show an appreciable charge transfer from the drug and carrier. The FU@C6N6 complex had a higher charge transfer (−0.16 e−) compared to the NU@C6N6 complex (−0.02 e−). Frontier molecular orbital (FMO) analysis reveals that the adsorption of FU on C6N6 caused a more pronounced decrease in the HOMO-LUMO gap (EH-L) compared to that of NU. The results of the FMO analysis are consistent with the NBO and EDD analyses. The drug release mechanism was studied through dipole moments and pH effects. The highest decrease in adsorption energy was observed for the FU@C6N6 complex in an acidic medium, which indicates that FU can easily be off-loaded from the carrier (C6N6) to a target site because the cancerous cells have a low pH compared to a normal cell. Thus, it may be concluded that C6N6 possesses the therapeutic potential to act as a nanocarrier for FU to treat cancer. Furthermore, the current study will also provide motivation to the scientific community to explore new surfaces for drug delivery applications

Hydrogen Dissociation Reaction on First-Row Transition Metal Doped Nanobelts

Zigzag molecular nanobelts have recently captured the interest of scientists because of their appealing aesthetic structures, intriguing chemical reactivities, and tantalizing features. In the current study, first-row transition metals supported on an H6-N3-belt[6]arene nanobelt are investigated for the electrocatalytic properties of these complexes for the hydrogen dissociation reaction (HDR). The interaction of the doped transition metal atom with the nanobelt is evaluated through interaction energy analysis, which reveals the significant thermodynamic stability of TM-doped nanobelt complexes. Electronic properties such as frontier molecular orbitals and natural bond orbitals analyses are also computed, to estimate the electronic perturbation upon doping. The highest reduction in the HOMO–LUMO energy gap compared to the bare nanobelt is seen in the case of the Zn@NB catalyst (4.76 eV). Furthermore, for the HDR reaction, the Sc@NB catalyst displays the best catalytic activity among the studied catalysts, with a hydrogen dissociation barrier of 0.13 eV, whereas the second-best catalytic activity is observed for the Zn@NB catalyst (0.36 eV). It is further found that multiple active sites, i.e., the presence of the metal atom and nitrogen atom moiety, help to facilitate the dissociation of the hydrogen molecule. These key findings of this study enhance the understanding of the relative stability, electronic features, and catalytic bindings of various TM@NB catalysts

Characterization of dredged sediments of Bouhanifia dam: potential use as a raw material

Dam silting has become a common problem due to the deleterious aspects that it generates, such as reducing both water quality (during turbid hydrodynamic events) and storage capacity of the reservoir. Various approaches of dam desilting have been undertaken to deal with this issue; however, the problem is far from being solved due to millions of cubic metres of sediments that are being trapped and not bypassing towards downstreams, which results in coastal erosion increment. This is particularly the case of the Bouhanifia dam in Algeria. So far, several geotechnical studies have been carried out aiming at evaluating this problem. The main objective of the current research study is the characterization of the dredged sediments of this dam for potential use as raw material to be harnessed for the construction industry. The valorization of the dam dredged sediments might include the mechanical stabilization in road construction, which reduces the excavation of natural qualified materials. The feasibility of using different fractions (5%, 10%, and 20%) of Bouhanifia dam dredged sediments as an admixture to the calcareous tuff which is a natural material usually applied in roads construction in Algeria is studied herein. A rough prediction of the long-term mechanical behaviour of the sediments and tuff is reported based on their physical, chemical, and mineralogical characteristics and short-term mechanical performance tests. The current study suggests the feasible use of tuff admixed sediments as embankment or subgrade materials; however, the long-term mechani-cal behaviour investigation of these materials is essential, and their mechanical stabilization is recommended to enhance their geomechanical behaviour as it is expected from the sediments to present lower strength when compared with the tuff

The Discreet charm of the lugubriosie (or The art of tiding oneself over): Thomas Bernhard's Extinction, trans. David McLintock, Penguin Books, London, 1996, pp. 335, RRP $16.95 (paper). [Book Review]

It's all here – the escalating hyperbole, the grandiosity, the connoisseurship, the importuning of the witness – the unmistakeable voice of one of Thomas Bernhard's protagonists holding out, fittingly enough, on the topic of exaggeration. On the occasion of the publication of Bernhard's biography, reviewed recently by Murray Bail in <i>The Age</i>,<a href="http://pandora.nla.gov.au/pan/20741/20020628-0000/www.arts.monash.edu.au/others/colloquy/current/Issue Six/Hanratty.htm#_edn2">[2]</a> I look at his last novel, <i>Extinction</i> and its fine contribution to the sensibility of lugubriousness