Agelasine Diterpenoids and Cbl-b Inhibitory Ageliferins from the Coralline Demosponge Astrosclera willeyana

An extract of the coralline demosponge Astrosclera willeyana inhibited the ubiquitin ligase activity of the immunomodulatory protein Cbl-b. The bioassay-guided separation of the extract provided ten active compounds, including three new N-methyladenine-containing diterpenoids, agelasines W–Y (1–3), a new bromopyrrole alkaloid, N(1)-methylisoageliferin (4), and six known ageliferin derivatives (5–10). The structures of the new compounds were elucidated from their spectroscopic and spectrometric data, including IR, HRESIMS, and NMR, and by comparison with spectroscopic data in the literature. While all of the isolated compounds showed Cbl-b inhibitory activities, ageliferins (4–10) were the most potent metabolites, with IC₅₀ values that ranged from 18 to 35 μM.     

Pharmacokinetics,efficacy and convulsive dose of articaine hydrochloride in goat kids

ObjectiveTo investigate the pharmacokinetics, efficacy and convulsive dose of articaine hydrochloride in goat kids.Study designExperimental prospective study.AnimalsA total of 18 (n = 6 animals per experiment) male Saanen goat kids (2–4 weeks old).MethodsThe study consisted of three experiments. The first determined the pharmacokinetics of articaine following intravenous administration of articaine hydrochloride (8 mg kg^–1). The second experiment investigated the anaesthetic efficacy and pharmacokinetics following cornual nerve block using 1.5% articaine hydrochloride. Anaesthesia of horn buds was evaluated using the response to pinprick test. Non-compartmental analysis was used. The final experiment determined the convulsive dose of articaine and its corresponding plasma concentration following intravenous infusion of articaine hydrochloride (4 mg kg^–1 minute^–1). Data are shown as mean ± standard deviation.ResultsThe mean terminal half-life (t_1/2λz), mean volume of distribution at steady state (Vd_ss) and mean plasma clearance (CL) of articaine following intravenous administration were 0.66 hour, 3.81 L kg^–1 and 5.33 L hour^–1 kg^–1, respectively. After cornual nerve block, the mean maximum plasma concentration of articaine was 587 ng mL^–1 at 0.22 hour and its mean t_1/2λz was 1.26 hours. Anaesthesia of horn buds was observed within 4 minutes following cornual nerve block. The mean dose required to produce convulsions was 16.24 mg kg^–1 and mean convulsive plasma concentrations of articaine and articainic acid were 9905 and 1517 ng mL^–1, respectively.ConclusionsIntravenous administration of 8 mg kg^–1 of articaine hydrochloride did not cause any adverse effects. Pharmacokinetic data suggest that articaine was rapidly eliminated and cleared. Cornual nerve block using 1.5% articaine hydrochloride alleviated the response to the acute nociceptive stimulus during disbudding.Clinical relevanceArticaine hydrochloride appears to be a safe and effective local anaesthetic for disbudding in goat kids.     

Assessing the distribution pattern of otters in four rivers of the Indian Himalayan biodiversity hotspot

1. The Eurasian otter (Lutra lutra), smooth‐coated otter (Lutrogale perspicillata), and Asian small‐clawed otter (Aonyx cinereus) have all been reported previously from the Indian state of Uttarakhand. However, little information is available about their current distribution in a mountainous region that is subject to increasing human‐induced stressors (such as hydropower plants, pollution, sand and boulder mining, destructive fishing techniques, poaching).
2. Owing to important roles played by these otters in structuring riverine food webs (particularly taking account of their roles as top carnivores), it is critical that they receive suitable protection in the face of projected temperature rise, change in precipitation patterns, and associated river flows in this Himalayan biodiversity hotspot. This study assesses otter distribution in four rivers of Uttarakhand as a basis for informing future conservation actions.
3. Field surveys were conducted (October 2018–January 2019) in reaches of the Kosi, Ramganga, Khoh, and Song rivers, supported by semi‐structured interviews (N = 379) conducted with members of local communities to collect qualitative data on views and perceptions of otter species. In addition, community‐based otter awareness camps were organized for local youths (N = 105), adults (N = 115), and schoolchildren (N = 256 covering 10 schools).
4. Habitat suitability maps were created using remote‐sensing data, survey findings, and a geographic information system to provide information about priority reaches of river to be targeted for future conservation efforts.
5. This study provides critical interdisciplinary baseline information to guide decision‐makers towards developing a targeted, otter‐specific conservation programme for this important Himalayan biodiversity hotspot.
6. The otter conservation education programmes conducted during this study resulted in a proposal to set up a community‐based conservation initiative to monitor and report otter sightings from the area, potentially representing a way forward for achieving simultaneous otter conservation and associated ecosystem benefits for local communities.

     

Potential impacts of non‐native fish on the threatened mahseer (Tor) species of the Indian Himalayan biodiversity hot spot

1. Mahseer (Tor) fish species are critical components of locally adapted freshwater food webs across the Indian Himalayan biodiversity hotspot; however, multiple human stressors compounded by climate change have significantly depleted their populations over recent decades.
2. Mahseer species are now considered locally vulnerable or endangered in many regions. Hydropower projects in particular have fragmented populations, impairing genetic exchange, obstructing migratory paths, and changing the structure and functioning of riverine habitats, especially of formerly fast‐flowing rivers.
3. Worryingly, a literature survey and group discussions reveal that the increasing spread of non‐native fish species further compounds threats to mahseer and overall freshwater ecology. A better understanding of the current distribution, habitat requirement, and dispersal of non‐native fish is therefore essential to manage the growing threats to mahseer in the Indian Himalayan region.

     

The kinesin Klp2 mediates polarization of interphase microtubules in fission yeast

Fission yeast (Schizosaccharomyces pombe) cells grow longitudinally in a manner dependent on a polarized distribution of their interphase microtubules. We found that this distribution required sliding of microtubules toward the cell center along preexisting microtubules. This sliding was mediated by the minus end-directed kinesin motor Klp2, which helped microtubules to become properly organized with plus ends predominantly oriented toward the cell ends and minus ends toward the cell center. Thus, interphase microtubules in the fission yeast require motor activities for their proper organization.     

Direct measurements of the convective recycling of the upper troposphere

We present a statistical representation of the aggregate effects of deep convection on the chemistry and dynamics of the upper troposphere (UT) based on direct aircraft observations of the chemical composition of the UT over the eastern United States and Canada during summer. These measurements provide unique observational constraints on the chemistry occurring downwind of convection and the rate at which air in the UT is recycled. These results provide quantitative measures that can be used to evaluate global climate and chemistry models.     

Controlled elimination of clathrin heavy-chain expression in DT40 lymphocytes

We exploited the high rate of homologous recombination shown by the chicken B cell line DT40 to inactivate the endogenous alleles for clathrin heavy chain and replace them with human clathrin complementary DNA under the control of a tetracycline-regulatable promoter. Clathrin repression perturbed the activities of Akt-mediated and mitogen-activated protein kinase-mediated signaling pathways and induced apoptosis; this finding suggests that in DT40 cells clathrin helps to maintain the integrity of antiapoptotic survival pathways. We also describe a variant cell line in which these signaling pathways were unaffected by clathrin down-regulation. This variant cell line did not undergo apoptosis in the absence of clathrin and was used to examine the effects of clathrin depletion on membrane-trafficking pathways. Receptor-mediated and fluid-phase endocytosis were both substantially inhibited, and transferrin-receptor recycling was modestly inhibited. Surprisingly, clathrin removal did not affect the morphology or biochemical composition of lysosomes.