A review of pharmacological effects of xylopic acid

Xylopic acid (15β-acetyloxy-kaur-16-en-19-oic acid) is a kaurene diterpene that can be obtained from various Xylopia spp. Xylopic acid has demonstrated several pharmacological activities in vitro and in vivo. The compound has shown promising effect as a potent analgesic, anti-inflammatory and anti-allergic agent. Xylopic acid is a CNS depressant and was able to ameliorate anxiety-like symptoms in mice in addition to its neuroprotective effects. Deleterious effects of xylopic acid on the reproductive system of mice have been well documented but extensive toxicity study detailing effect of the acid upon chronic exposure needs to be determined. Due to the heavy consumption of X. aethiopica fruits, it is recommended that the pharmacokinetics of xylopic acid be determined to ascertain the possible food-drug interaction that may occur when conventional drugs are taken together with foods containing xylopic acid

Manganese-Iron Phosphate Nodules at the Groken Site, Gale Crater, Mars

The MSL Curiosity rover investigated dark, Mn-P-enriched nodules in shallow lacustrine/fluvial sediments at the Groken site in Glen Torridon, Gale Crater, Mars. Applying all relevant information from the rover, the nodules are interpreted as pseudomorphs after original crystals of vivianite, (Fe2+,Mn2+)3(PO4)2·8H2O, that cemented the sediment soon after deposition. The nodules appear to have flat faces and linear boundaries and stand above the surrounding siltstone. ChemCam LIBS (laser-induced breakdown spectrometry) shows that the nodules have MnO abundances approximately twenty times those of the surrounding siltstone matrix, contain little CaO, and have SiO2 and Al2O3 abundances similar to those of the siltstone. A deconvolution of APXS analyses of nodule-bearing targets, interpreted here as representing the nodules’ non-silicate components, shows high concentrations of MnO, P2O5, and FeO and a molar ratio P/Mn = 2. Visible to near-infrared reflectance of the nodules (by ChemCam passive and Mastcam multispectral) is dark and relatively flat, consistent with a mixture of host siltstone, hematite, and a dark spectrally bland material (like pyrolusite, MnO2). A drill sample at the site is shown to contain minimal nodule material, implying that analyses by the CheMin and SAM instruments do not constrain the nodules’ mineralogy or composition. The fact that the nodules contain P and Mn in a small molar integer ratio, P/Mn = 2, suggests that the nodules contained a stoichiometric Mn-phosphate mineral, in which Fe did (i.e., could) not substitute for Mn. The most likely such minerals are laueite and strunzite, (Fe2+,Mn2+)3(PO4)2·8H2O and –6H2O, respectively, which occur on Earth as alteration products of other Mn-bearing phosphates including vivianite. Vivianite is a common primary and diagenetic precipitate from low-oxygen, P-enriched waters. Calculated phase equilibria show Mn-bearing vivianite could be replaced by laueite or strunzite and then by hematite plus pyrolusite as the system became more oxidizing and acidic. These data suggest that the nodules originated as vivianite, forming as euhedral crystals in the sediment, enclosing sediment grains as they grew. After formation, the nodules were oxidized—first to laueite/strunzite yielding the diagnostic P/Mn ratio, and then to hematite plus an undefined Mn oxy-hydroxide (like pyrolusite). The limited occurrence of these Mn-Fe-P nodules, both in space and time (i.e., stratigraphic position), suggests a local control on their origin. By terrestrial analogies, it is possible that the nodules precipitated near a spring or seep of Mn-rich water, generated during alteration of olivine in the underlying sediments

Registered Ship Notes

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Retroviral RNA dimerization and packaging.

<p>The description of retrovirus genomic RNA dimerization and packaging is based on a representative co-infected cell and depicts properties of C-type retroviruses such as HIV-1 and MLV. Note that this figure represents concepts schematically and is not intended to accurately represent structures or scale. (A) <i>What is packaged:</i> two genetically complete but nicked copies of plus sense gRNA (shown in red at top or green at bottom) are packaged within the capsid core and joined by a dimer linkage. The co-packaged gRNAs are condensed in the core and bound by NC (shown as green circles). (B) <i>How gRNAs are recruited:</i> initial gRNA dimerization occurs via kissing interactions between palindromic stem loops. Subsequent basepairing register-shifts that occur during dimer linkage maturation expose single-stranded NC binding motifs (indicated in yellow) that were previously basepaired and thus sequestered in gRNA monomers, allowing for Gag binding during recruitment. (C) <i>When gRNAs associate in dimers:</i> the point at which RNA dimerization partners first associate is different for HIV-1 and MLV. MLV gRNA dimers first associate near sites of transcription in the nucleus, which leads to disproportionately large amounts of one homodimer or the other (shown in red at top and green at bottom). HIV-1 gRNA dimers first associate in the cytoplasm, leading to a random assortment of homodimeric and heterodimeric gRNAs. (D) <i>Where gRNAs join assembling virions:</i> gRNAs may form subassemblies with Gag in the cytoplasm (shown at top) or may associate at the plasma membrane (shown at bottom) after active transport separate from all or most Gags. (E) <i>Why two gRNAs are packaged:</i> the packaging of two gRNAs may aid in packaging specificity as well as the promotion of genomic integrity. In addition, the packaging of two genetically distinct gRNAs (shown as a red/green heterodimer) promotes genetic recombination, which leads to genetic diversity in viral progeny.</p

Behavioural microclimate selection and physiological responses to environmental conditions in a hibernating bat

Hibernators adjust the expression of torpor behaviourally and physiologically to balance the benefits of energy conservation in hibernation against the physiological and ecological costs. Small fat-storing species, like many cave-hibernating bats, have long been thought to be highly constrained in their expression of hibernation because they must survive winter relying only on endogenous energy stores. We evaluated behavioural microclimate selection in tri-colored bats (Perimyotis subflavus (Cuvier, 1832)) across a three-month hibernation experiment under laboratory conditions. We also opportunistically tested for evidence of acclimatization in torpid metabolic rate (TMR). When given access to gradients in microclimate, bats tended to choose the warmest temperature available (11C) while almost completely avoiding the driest condition available (85% relative humidity at 8C). Further, bats held at different temperatures over the course of the hibernation showed no differences in TMR when measured under common conditions at the end of hibernation. Taken together, our results suggest selective pressures to conserve energy during hibernation are not overwhelmingly strong and further support the proposition that optimal expression of hibernation is something less than the maximal expression of hibernation unless the animal is nearing starvation.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Attractive targeted sugar bait phase III trials in Kenya, Mali, and Zambia

Background: Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) target night-time indoor biting mosquitoes and effectively reduce malaria transmission in rural settings across Africa, but additional vector control tools are needed to interrupt transmission. Attractive targeted sugar baits (ATSBs) attract and kill mosquitoes, including those biting outdoors. Deployment of ATSBs incorporating the insecticide dinotefuran was associated with major reductions in mosquito density and longevity in Mali. The impact of this promising intervention on malaria transmission and morbidity now needs to be determined in a range of transmission settings. Methods/design: We will conduct three similar stand-alone, open-label, two-arm, cluster-randomized, controlled trials (cRCTs) in Mali, Kenya, and Zambia to determine the impact of ATSB + universal vector control versus universal vector control alone on clinical malaria. The trials will use a “fried-egg” design, with primary outcomes measured in the core area of each cluster to reduce spill-over effects. All household structures in the ATSB clusters will receive two ATSBs, but the impact will be measured in the core of clusters. Restricted randomization will be used. The primary outcome is clinical malaria incidence among children aged 5–14 years in Mali and 1–14 years in Kenya and Zambia. A key secondary outcome is malaria parasite prevalence across all ages. The trials will include 76 clusters (38 per arm) in Mali and 70 (35 per arm) in each of Kenya and Zambia. The trials are powered to detect a 30% reduction in clinical malaria, requiring a total of 3850 person-years of follow-up in Mali, 1260 person-years in Kenya, and 1610 person-years in Zambia. These sample sizes will be ascertained using two seasonal 8-month cohorts in Mali and two 6-month seasonal cohorts in Zambia. In Kenya, which has year-round transmission, four 6-month cohorts will be used (total 24 months of follow-up). The design allows for one interim analysis in Mali and Zambia and two in Kenya. Discussion: Strengths of the design include the use of multiple study sites with different transmission patterns and a range of vectors to improve external validity, a large number of clusters within each trial site, restricted randomization, between-cluster separation to minimize contamination between study arms, and an adaptive trial design. Noted threats to internal validity include open-label design, risk of contamination between study arms, risk of imbalance of covariates across study arms, variation in durability of ATSB stations, and potential disruption resulting from the COVID-19 pandemic. Trial registration: Zambia: ClinicalTrials.gov NCT04800055. Registered on March 15, 2021 Mali: ClinicalTrials.gov NCT04149119. Registered on November 4, 2019 Kenya: ClinicalTrials.gov NCT05219565. Registered on February 2, 2022