Block of nicotinic acetylcholine receptors by philanthotoxins is strongly dependent on their subunit composition

Philanthotoxin-433 (PhTX-433) is an active component of the venom from the Egyptian digger wasp, Philanthus triangulum. PhTX-433 inhibits several excitatory ligand-gated ion channels, and to improve selectivity two synthetic analogues, PhTX-343 and PhTX-12, were developed. Previous work showed a 22-fold selectivity of PhTX-12 over PhTX-343 for embryonic muscle-type nicotinic acetylcholine receptors (nAChRs) in TE671 cells. We investigated their inhibition of different neuronal nAChR subunit combinations as well as of embryonic muscle receptors expressed in Xenopus oocytes. Whole-cell currents in response to application of acetylcholine alone or co-applied with PhTX analogue were studied by using two-electrode voltage-clamp. α3β4 nAChRs were most sensitive to PhTX-343 (IC50=12 nM at −80 mV) with α4β4, α4β2, α3β2, α7 and α1β1γδ being 5, 26, 114, 422 and 992 times less sensitive. In contrast α1β1γδ was most sensitive to PhTX-12 along with α3β4 (IC50values of 100 nM) with α4β4, α4β2, α3β2 and α7 being 3, 3, 26 and 49 times less sensitive. PhTX-343 inhibition was strongly voltage-dependent for all subunit combinations except α7, whereas this was not the case for PhTX-12 for which weak voltage dependence was observed. We conclude that PhTX-343 mainly acts as an open-channel blocker of nAChRs with strong subtype selectivity

Accommodating individual travel history and unsampled diversity in Bayesian phylogeographic inference of SARS-CoV-2

Spatiotemporal bias in genome sampling can severely confound discrete trait phylogeographic inference. This has impeded our ability to accurately track the spread of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, despite the availability of unprecedented numbers of SARS-CoV-2 genomes. Here, we present an approach to integrate individual travel history data in Bayesian phylogeographic inference and apply it to the early spread of SARS-CoV-2. We demonstrate that including travel history data yields i) more realistic hypotheses of virus spread and ii) higher posterior predictive accuracy compared to including only sampling location. We further explore methods to ameliorate the impact of sampling bias by augmenting the phylogeographic analysis with lineages from undersampled locations. Our reconstructions reinforce specific transmission hypotheses suggested by the inclusion of travel history data, but also suggest alternative routes of virus migration that are plausible within the epidemiological context but are not apparent with current sampling efforts.status: publishe

What is information? Toward a theory of information as objective and veridical

Information systems are a strong and ever-growing discipline of enormous relevance to today’s informated world, and yet, as recent reviews have shown, there is still not an agreed and explicit conceptualization or definition of information. After an evaluative review of a range of theories of information, this paper develops and defends a particular theory, one that sees information as both objective and veridical. By objective, we mean that the information carried by signs and messages exists independently of its receivers or observers. The information carried by a sign exists even if the sign is not actually observed. By veridical, we mean that information must be true or correct in order to be information – information is truth-constituted. False information is not information, but misinformation or disinformation. The paper develops this theory and then discusses four contentious issues – information as objective rather than subjective; information as true or correct; information and knowledge; and information and the ambiguity of meaning. It concludes with a discussion of the practical implications of the theory

Impact of physical and enzymatic cell wall opening on the release of pre-gelatinized starch and viscosity forming potential of potato flakes

Potato flakes (PFs) are used in instant foods. They contain pre-gelatinized starch which readily develops viscosity upon hydration. We here provide the first report on factors influencing their viscosifying potential. Swelling power (SP) (r = 0.719, p < 0.01) and mean particle size (r = -0.704, p < 0.05) mainly determine instant viscosity development of PF suspensions while short extractable extracellular amylose molecules [degree of polymerization between 150 and 1500 (EE-AM150-1500)] positively impact their cold paste viscosity (CPV) (r = 0.717, p < 0.01) in Rapid Visco Analyzer (RVA) models. Cell wall opening by ball milling or cellulase treatments increased PF SP resulting in up to 75% higher RVA peak viscosity readings. Furthermore, the release of EE-AM150-1500 molecules increased CPV by about 30% since they readily associated upon cooling. Partial cell wall opening thus improves the viscosifying potential of PFs and expands their applicability in instant foods.status: publishe

Amylolysis as a tool to control amylose chain length and to tailor gel formation during potato-based crisp making

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Structure, chemical composition and enzymatic activities of pearlings and bran obtained from pearled wheat (Triticum aestivum L.) by roller milling

While abrasive pearling (also referred to as debranning) of wheat kernels prior to milling increases the quality of the resultant flour for producing bread, the potential applications of the co-products of pearling is largely unknown. We studied the impact of different degrees of pearling (0, 3, 6, 9 and 12% by weight) on the composition of pearlings and bran obtained when subsequently roller milling pearled wheat kernels. Pearling does not remove the kernel outer tissues homogeneously as abrasion affects especially the accessible parts of the kernels. Nevertheless, the first 3% removed consisted of mainly pericarp. With 6% or more removed, a significant amount of starchy endosperm ended up in the pearlings. The starting bran material and bran obtained by subsequent roller milling of pearled wheat kernels had similar compositions but the latter had a lower average particle size. Moreover, removal of the outermost kernel layers substantially decreased the enzyme activity levels in the bran.publisher: Elsevier articletitle: Structure, chemical composition and enzymatic activities of pearlings and bran obtained from pearled wheat (Triticum aestivum L.) by roller milling journaltitle: Journal of Cereal Science articlelink: http://dx.doi.org/10.1016/j.jcs.2014.12.009 content_type: article copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.status: publishe

Prevention of adjustment disorders and anticipatory nausea secondary to adjuvant chemotherapy: a double-blind, placebo-controlled study assessing the usefulness of alprazolam.

PURPOSE AND METHODS: Although a high prevalence of adjustment disorders and anticipatory nausea secondary to adjuvant chemotherapy (CT) has been reported, little has been done to develop strategies to prevent these problems. A double-blind, placebo-controlled study was therefore designed to assess the usefulness of adding low-dose alprazolam (0.5 mg to 2 mg per day) to a psychologic support program including progressive relaxation training designed to prevent the aforementioned conditions. Fifty-seven women undergoing adjuvant CT for stage II primary breast cancer agreed to participate in the assessment, which was conducted at four time points: before starting CT, 6 weeks after CT, before the fourth CT, and after the fourth CT. The Hospital Anxiety and Depression Scale (HADS), Montgomery and Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Scale (HAS), Revised Symptom Checklist (SCL-90-R), Morrow Assessment of Nausea and Emesis (MANE), and World Health Organization (WHO) grading of acute and subacute toxicities were used to compare the alprazolam (AA) and placebo (PA) arms of the study. RESULTS: At the second evaluation, the results showed a higher rate of anticipatory nausea (18% v 0%) in the PA compared with the AA arm (P = .038). These differences were no more significant at each of the further assessments. Significant differences were found for the intake of hypnotics at each assessment visit, with the rate of hypnotic users being significantly higher in the PA (19%) compared with the AA (0%) arm at the fourth assessment (P < .05). Anxiety and depression scores of self- and observer-report were similar in the two arms. A significant relationship was found between the development of anticipatory nausea and the self-report of anxiety and depression score measured by HADS at baseline. The average HADS total score at baseline was 15.33 (SD = 6.56) for patients who developed anticipatory nausea and 11.23 (SD = 6.67) for other patients. CONCLUSION: The adjunct of alprazolam to a psychologic support program delays the occurrence of anticipatory nausea and controls sleeping problems secondary to adjunct CT. Although studies are needed to improve the efficacy reported here, physicians may already consider the use of alprazolam for cancer patients undergoing CT.Clinical TrialControlled Clinical TrialJournal ArticleRandomized Controlled TrialResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe