57 research outputs found

    Isolation, characterization and antifungal docking studies of wortmannin isolated from Penicillium radicum

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    During the search for a potent antifungal drug, a cell-permeable metabolite was isolated from a soil isolate taxonomically identified as Penicillium radicum. The strain was found to be a potent antifungal agent. Production conditions of the active compound were optimized and the active compound was isolated, purified, characterized and identified as a phosphoinositide 3-kinase (PI3K) inhibitor, commonly known as wortmannin (Wtmn). This is very first time we are reporting the production of Wtmn from P. radicum. In addition to its previously discovered anticancer properties, the broad spectrum antifungal property of Wtmn was re-confirmed using various fungal strains. Virtual screening was performed through molecular docking studies against potential antifungal targets, and it was found that Wtmn was predicted to impede the actions of these targets more efficiently than known antifungal compounds such as voriconazole and nikkomycin i.e. 1) mevalonate-5-diphosphate decarboxylase (1FI4), responsible for sterol/isoprenoid biosynthesis; 2) exocyst complex component SEC3 (3A58) where Rho-and phosphoinositide-dependent localization is present and 3) Kre2p/Mnt1p a Golgi alpha1,2-mannosyltransferase (1S4N) involved in the biosynthesis of yeast cell wall glycoproteins). We conclude that Wtmn produced from P. radicum is a promising lead compound which could be potentially used as an efficient antifungal drug in the near future after appropriate structural modifications to reduce toxicity and improve stability.Peer reviewe

    Competition between normal and intruder states inside the "Island of Inversion"

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    The beta decay of the exotic 30Ne (N=20) is reported. For the first time, the low-energy level structure of the N=19, 30Na (Tz = 4), is obtained from beta-delayed gamma spectroscopy using fragment-beta-gamma-gamma coincidences. The level structure clearly displays "inversion", i.e., intruder states with mainly 2p2h configurations displacing the normal states to higher excitation energies. The good agreement in excitation energies and the weak and electromagnetic decay patterns with Monte Carlo Shell Model calculations with the SDPF-M interaction in the sdpf valence space illustrates the small d3/2 - f7/2 shell gap. The relative position of the "normal dominant" and "intruder dominant" excited states provides valuable information to understand better the N=20 shell gap.Comment: 4 pages, 5 figure

    Understanding Excitations in 59,61^{59,61}Co, 59^{59}Ni

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    High spin states in 59^{59}Co (Z=27Z=27), 59^{59}Ni (Z=28Z=28) and 61^{61}Co have been populated by the fusion evaporation reactions, 48^{48}Ti(14^{14}C, p2n)59^{59}Co, 48^{48}Ti(14^{14}C, 3n)59^{59}Ni, and 50^{50}Ti(14^{14}C, p2n)61^{61}Co. The 9 MV tandem accelerator at the John D Fox Laboratory, Florida State University (FSU) was used to accelerate the 14^{14}C beam and the de-exciting γ\gamma rays were detected by the FSU detector array consisting of six High Purity Germanium (HPGe) clover detectors, and three single crystals. Directional correlation of the γ\gamma rays de-exciting oriented states (DCO ratios) and polarization asymmetry measurements helped to establish spin and parities of the excited states whenever possible. The level scheme of 59^{59}Co has been expanded with the inclusion of positive parity states up to 31/2+^+ at around 11 MeV. The 59^{59}Ni positive parity states known from previous study were verified with modifications to some of the spins and parities. On the other hand, the negative parity states were extended to 31/2 at an excitation energy of 12 MeV. No new transition was observed for 61^{61}Co, but one of the major bands has been reassigned as consisting of positive parity states by reason of this study which is a candidate for magnetic rotation band. Cross shell excitations were observed in the three nuclei studied and the prominent role of excitation to g9/2_{9/2} orbital crossing the N=40N=40 shell gap was established in relation to collective excitation in these nuclei by comparison with large-scale shell model calculations

    Cross-shell excitations in Si 31

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    The Si31 nucleus was produced through the O18(O18, αn) fusion-evaporation reaction at Elab=24MeV. Evaporated α particles from the reaction were detected and identified in the Microball detector array for channel selection. Multiple γ-ray coincidence events were detected in Gammasphere. The energy and angle information for the α particles was used to determine the Si31 recoil kinematics on an event-by-event basis for a more accurate Doppler correction. A total of 22 new states and 52 new γ transitions were observed, including 14 from states above the neutron separation energy. The positive-parity states predicted by the shell-model calculations in the sd model space agree well with experiment. The negative-parity states were compared with shell-model calculations in the psdpf model space with some variations in the N=20 shell gap. The best agreement was found with a shell gap intermediate between that originally used for A≈20 nuclei and that previously adapted for P32,34. This variation suggests the need for a more universal cross-shell interaction

    Fistula recurrence, pregnancy, and childbirth following successful closure of female genital fistula in Guinea : a longitudinal study

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    Background: Female genital fistula is a devastating maternal complication of delivery in developing countries. We sought to analyse the incidence and proportion of fistula recurrence, residual urinary incontinence, and pregnancy after successful fistula closure in Guinea, and describe the delivery-associated maternal and child health outcomes. Methods: We did a longitudinal study in women discharged with a closed fistula from three repair hospitals supported by Engender Health in Guinea. We recruited women retrospectively (via medical record review) and prospectively at hospital discharge. We used Kaplan-Meier methods to analyse the cumulative incidence, incidence proportion, and incidence ratio of fistula recurrence, associated outcomes, and pregnancy after successful fistula closure. The primary outcome was recurrence of fistula following discharge from repair hospital in all eligible women who consented to inclusion and could provide follow-up data. Findings: 481 women eligible for analysis were identified retrospectively (from Jan 1, 2012, to Dec 31, 2014; 348 women) or prospectively (Jan 1 to June 20, 2015; 133 women), and followed up until June 30, 2016. Median follow-up was 28.0 months (IQR 14.6-36.6). 73 recurrent fistulas occurred, corresponding to a cumulative incidence of 71 per 1000 person-years (95% CI 56.5-89.3) and an incidence proportion of 18.4% (14.8-22.8). In 447 women who were continent at hospital discharge, we recorded 24 cases of post-repair residual urinary incontinence, equivalent to a cumulative incidence of 23.1 per 1000 person-years (14.0-36.2), and corresponding to 10.3% (5.2-19.6). In 305 women at risk of pregnancy, the cumulative incidence of pregnancy was 106.0 per 1000 person-years, corresponding to 28.4% (22.8-35.0) of these women. Of 50 women who had delivered by the time of follow-up, only nine delivered by elective caesarean section. There were 12 stillbirths, seven delivery-related fistula recurrences, and one maternal death. Interpretation: Recurrence of female genital fistula and adverse pregnancy-related maternal and child health outcomes were frequent in women after fistula repair in Guinea. Interventions are needed to safeguard the health of women after fistula repair
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