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Background: According to the World Health Organization, osteoarthritis (OA) is one of the 10 most disabling diseases in developed countries, with worldwide estimates of 9.6% prevalence in men and 18.0% in women over 60 years old. Its management is not well established and involves the use of high doses of painkillers coupled with anti-inflammatory agents. Objective: In the search for alternatives to manage the disease, previous studies have shown superi-or properties of Q-ActinTM in managing OA-related pain compared with standard treatments. Q-actin is a cucumber extract with the anti-inflammatory iminosugar idoBR1 standardised to over 1%. This study investigated the effects of different doses (20 mg, 100 mg) of Q-Actin in a longitudinal placebo-controlled experiment. Methods: There were 101 patients with knee OA enrolled for the 180-day study, with 91 patients completing it. Patients were grouped into a placebo group (PLBO), as well as a 20mg dose (Q-Actin 1) and 100 mg dose (Q-Actin 2) groups. The PLBO group received cellulose in capsules identical to the Q-Actin capsules. Results: There was a significant improvement in the pain-related parameters over time that was dose-dependent. Conclusion: This study clearly demonstrated the effectiveness of Q-Actin compared to placebo in the management of pain related to moderate osteoarthritis.

This special issue honours James Ost's (1973-2019) contributions to our understanding of false and distorted remembering. In our editorial, we introduce some of James' distinctive research themes including the experiences of people who retract "recovered" memories, social (e.g., co-witness and interviewer influence) and personality influences on false remembering, the nature of false remembering itself (e.g., different types of false memories; false memories vs. false beliefs), public understanding of (false) memory, and a historical link to the work of Frederic Bartlett. We illustrate these themes through a number of key publications. The unifying thread behind James' work is his core interest in false/distorted remembering in real-life (typically high-stake) situations, in line with his engagement with the British False Memory Society and his role as an expert witness in court trials. The articles included in this special issue elaborate on the research themes to which James devoted his career and his curiosity.

As one of the first model organism knowledgebases, Saccharomyces Genome Database (SGD) has been supporting the scientific research community since 1993. As technologies and research evolve, so does SGD: from updates in software architecture, to curation of novel data types, to incorporation of data from, and collaboration with, other knowledgebases. We are continuing to make steps toward providing the community with an S. cerevisiae pan-genome. Here, we describe software upgrades, a new nomenclature system for genes not found in the reference strain, and additions to gene pages. With these improvements, we aim to remain a leading resource for students, researchers, and the broader scientific community.

Symptoms and complications associated with severe SARS-CoV-2 infection such as acute respiratory distress syndrome (ARDS) and organ damage have been linked to SARS-CoV-2 spike protein S1-induced increased production of pro-inflammatory cytokines by immune cells. In this study, the effects of an extract of Garcinia kola seeds and garcinoic acid were investigated in SARS-CoV-2 spike protein S1-stimulated human PBMCs. Results of ELISA experiments revealed that Garcinia kola extract (6.25, 12.5, and 25 µg/ml) and garcinoic acid (1.25, 2.5, and 5 µM) significantly reduced SARS-CoV-2 spike protein S1-induced secretion of TNFα, IL-6, IL-1s, and IL-8 in PBMCs. In-cell western assays showed that pre-treatment with Garcinia kola extract and garcinoic acid reduced expressions of both phospho-p65 and phospho-IκBα proteins, as well as NF-κB DNA binding capacity and NF-κB-driven luciferase expression following stimulation of PBMCs with spike protein S1. Furthermore, pre-treatment of PBMCs with Garcinia kola extract prior to stimulation with SARS-CoV-2 spike protein S1 resulted in reduced damage to adjacent A549 lung epithelial cells. These results suggest that the seed of Garcinia kola and garcinoic acid are natural products which may possess pharmacological/therapeutic benefits in reducing cytokine storm in severe SARS-CoV-2 and other coronavirus infections.

Feedback is invaluable for learning, yet people frequently fail to remember their feedback. Recent studies have demonstrated that people are better at recalling evaluative, past-oriented feedback than directive, future-oriented feedback. This paper tests one possible explanation: namely, that people neglect to search their memory for directive information they have encoded. Participants (N = 759), attempted to recall feedback they had read about their own (Experiment 1) or another person's performance (Experiments 2A−4). We attempted to foster recall of directive feedback via a structured recall task (Experiments 1−2B) or a perspective-taking instruction (Experiment 3). All experiments replicated the preferential recall of evaluative feedback, but our manipulations did not moderate this bias. Experiment 4 replicated the bias using non-educational feedback, and provided tentative indications that it might not translate beyond the feedback domain. The data suggest that selective retrieval processes are not responsible for people's poor recall of directive feedback.

Purpose. Rapport-building has beneficial effects in investigative and security contexts. However, there remains limited understanding of the extent of agreement between different parties in their judgments of rapport.\ud Methods. We observed 133 mock suspect interviews, and subsequently surveyed the lead interviewer and secondary interviewer (trainees undertaking an undergraduate Policing programme), the ‘suspect’ (an actor), and an expert observer (a retired, highly experienced police detective). Each of these parties provided subjective judgments of the degree of rapport that had been formed between suspect and lead interviewer. Furthermore, we assessed whether these subjective judgments were associated with the degree of ‘Language Style Matching’ (LSM) between lead interviewer and suspect: a key linguistic measure of interpersonal synchrony.\ud Results. The suspect, secondary interviewer, and expert observer had generally good agreement about the degree of rapport achieved, as evidenced through significant, moderate to strong correlations between their rapport ratings. However, these parties’ rapport ratings were weakly associated with those of the lead interviewer. Our linguistic analysis provided similar results: the extent of LSM was significantly associated with suspects’ and the expert’s subjective ratings of rapport, but not with the interviewers’ ratings.\ud Conclusions. The findings suggest that the demands of interviewing might impede interviewers’ insight into the success of their rapport-building efforts, leading them to overlook cues that other parties rely upon. We discuss the need for future experimental manipulations to directly test this suggestion, and we consider the value of interpersonal synchrony in defining and measuring rapport.

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The absolute stereochemistry of the marine alkaloid (+)-(R)-tiruchanduramine was established via a convergent total synthesis in six steps and 15.5% overall yield from Fmoc-D-Dab(Boc)-OH.

Averting gaze from another person’s face generally improves cognitive performance, yet, little is known about how witnesses’ gaze direction affects their recall during investigative interviews. Here, participants witnessed a video-recorded incident, and were interviewed via free recall and closed questions following a short delay. In Experiment 1, participants either faced the interviewer or faced away during the interview. In Experiment 2, alongside this manipulation, the interviewer also either faced the witness or faced away. In Experiment 3, witness gaze direction was manipulated alongside rapport-building. In Experiment 4, the effect of facing away was directly compared with that of eye-closure. Mini meta-analysis of all four experiments showed that the effect of witness gaze direction on memory performance was minimal. Furthermore, neither aversion of interviewer’s gaze nor rapport-building magnified this effect. Added to the cumulative literature on eyewitness gaze aversion, these findings afford better estimates of the likely size of these effects.

Many policies and processes in higher education reinforce a conception of feedback as being the transmission of information, thus placing primary responsibility on educators for delivering this information ‘well’ whilst neglecting the essential responsibilities of learners. In this study, 216 university educators described the responsibilities of students, and of educators themselves, in the feedback process. We analysed their responses using both content analysis and a novel linguistic analysis of the specific words used. The content analysis indicated a clear influence of transmission-based models of feedback on educators’ views, with educators seen as responsible primarily for providing comments, and students responsible primarily for processing these comments. Linguistically, educators conveyed greater certainty and were more likely to use referents to power and positive emotion, when describing their own as opposed to students’ responsibilities. These findings underscore the necessity of a cultural shift toward responsibility-sharing in the context of feedback in higher education.

The absolute stereochemistry of the marine alkaloid (

Saccharomyces cerevisiae is used to provide fundamental understanding of eukaryotic genetics, gene product function, and cellular biological processes. Saccharomyces Genome Database (SGD) has been supporting the yeast research community since 1993, serving as its de facto hub. Over the years, SGD has maintained the genetic nomenclature, chromosome maps, and functional annotation, and developed various tools and methods for analysis and curation of a variety of emerging data types. More recently, SGD and six other model organism focused knowledgebases have come together to create the Alliance of Genome Resources to develop sustainable genome information resources that promote and support the use of various model organisms to understand the genetic and genomic bases of human biology and disease. Here we describe recent activities at SGD, including the latest reference genome annotation update, the development of a curation system for mutant alleles, and new pages addressing homology across model organisms as well as the use of yeast to study human disease.

Alchornea cordifolia Müll. Arg. (commonly known as Christmas Bush) has been used traditionally in Africa to treat sickle cell anaemia (a recessive disease, arising from the S haemoglobin [Hb] allele) but the active compounds are yet to be characterised. Herein we describe the use of sequential fractionation coupled with in vitro anti-sickling assays to purify the active component. Sickling was induced in HbSS genotype blood samples using sodium metabisulphite (Na2S2O5) or incubation in 100 % N2. Methanol extracts of A. cordifolia leaves and its sub-fractions showed >70 % suppression of HbSS erythrocyte sickling. Purified compound demonstrated 87.2 ± 2.39 % significant anti-sickling activity and 93.1 ± 2.69 % erythrocyte sickling-inhibition at 0.4 mg/mL. Nuclear magnetic resonance (NMR) spectra and high-resolution mass spectroscopy identified it as quercitrin (quercetin 3-rhamnoside). Purified quercitrin also inhibited the polymerisation of isolated HbS and stabilized sickle erythrocytes membranes. Metabolomic comparisons of blood samples using flow-infusion electrospray-high resolution mass spectrometry indicated that quercitrin could convert HbSS erythrocyte metabolomes to be similar to HbAA. Sickling was associated with changes in anti-oxidants, anaerobic bioenergy and arachidonic acid metabolism, all of which were reversed by quercitrin. The findings described could inform efforts directed to the development of an anti-sickling drug or quality control assessments of A. cordifolia preparations.

Front-of-pack health imagery can shape people's inferences about food products' health benefits, even leading people to falsely remember reading health claims they never saw. However, research has typically examined these effects in situations where participants have little contextual information to guide their inferences about a product. The present research aimed to replicate the finding that front-of-pack health imagery leads participants to falsely remember reading health claims. It also extends that finding, by exploring whether this effect is moderated by the presence of contextual information signaling the product's actual 'healthiness'. In two pre-registered experiments, participants saw images of fictitious food products accompanied by written nutrition claims. Some of the products contained a health-related image whereas others did not. The supposed 'healthiness' of each product was manipulated by altering the color of the products' multiple traffic light (MTL) label (Experiment 1), or with an explicit healthiness statement (Experiment 2). Participants then attempted to remember the written claims that had appeared on each product's packaging. Health-related images increased participants' tendency to falsely remember reading health claims. But this was true regardless of whether or not participants saw contextual cues about the products' healthiness, either indirectly (Experiment 1) or directly (Experiment 2). These findings suggest that the presence of health imagery on a food product's package can lead consumers to infer health benefits, even when other, more direct cues indicate that the product is unhealthy. This research informs debates on safeguarding consumers from potentially misleading health claims, through the regulation of imagery in food marketing.

Symptoms and complications associated with severe SARS-CoV-2 infection such as acute respiratory distress syndrome (ARDS) and organ damage have been linked to SARS-CoV-2 spike glycoprotein S1-induced increased production of pro-inflammatory cytokines by immune cells. In this study, the effects of an extract of Garcinia kola seeds and garcinoic acid were investigated in SARS-CoV-2 spike glycoprotein S1-stimulated human PBMCs. Results of ELISA experiments revealed that Garcinia kola extract (6.25, 12.5 and 25 μg/mL) and garcinoic acid (1.25, 2.5 and 5 μM) significantly reduced SARS-CoV-2 spike glycoprotein S1-induced increased secretion of TNFα, IL-6, IL-1β and IL-8 in PBMCs. In-cell western assays showed that pre-treatment with Garcinia kola extract and garcinoic acid reduced elevated expressions of both phospho-p65 and phospho-κBα proteins, as well as NF-κB DNA binding capacity and NF-κB-driven luciferase expression following stimulation of PBMCs with spike glycoprotein S1. Furthermore, pre-treatment of PBMCs with Garcinia kola extract prior to stimulation with SARS-CoV-2 spike glycoprotein S1 resulted in reduced damage to adjacent A549 lung epithelial cells. Gas Chromatography-Mass Spectrometry (GCMS) and HPLC-PDA confirmed the presence of garcinoic acid in the Garcinia kola extract used in this study. These results suggest that the seed of Garcinia kola and garcinoic acid are natural products which may possess pharmacological/therapeutic benefits in reducing cytokine storm during the late stage of severe SARS-CoV-2 and other coronavirus infections.

Exposure to fake news stories can result in false memories for the events portrayed, and this effect can be enhanced if the stories conform to the reader's ideological position. We exposed 1299 UK residents to fabricated news stories about Brexit. 44% of participants reported a false memory for at least one fabricated story, with a higher rate of false memories for stories that reflected poorly on the opposing side. This effect of ideological congruency was somewhat greater among participants who were exposed to a threat to their social identity as a Leave or Remain supporter; however, this moderating effect was only statistically significant in exploratory analyses using a more conservative definition of false memory. Participants with higher cognitive ability and analytical reasoning scores were less susceptible to false memories. Individuals with better knowledge about Brexit showed better discrimination between true and false stories, while self-reported engagement with the Brexit debate was associated with an increased tendency to "remember" any story, regardless of its truth. These results implicate a combination of social and individual factors in the development of false memories from fake news, and suggest that exposure to social identity threats may enhance the polarising effects of fake news.

The Saccharomyces Genome Database (SGD; www.yeastgenome.org) maintains the official annotation of all genes in the Saccharomyces cerevisiae reference genome and aims to elucidate the function of these genes and their products by integrating manually curated experimental data. Technological advances have allowed researchers to profile RNA expression and identify transcripts at high resolution. These data can be configured in web-based genome browser applications for display to the general public. Accordingly, SGD has incorporated published transcript isoform data in our instance of JBrowse, a genome visualization platform. This resource will help clarify S. cerevisiae biological processes by furthering studies of transcriptional regulation, untranslated regions, genome engineering, and expression quantification in S. cerevisiae.

The Alliance of Genome Resources (Alliance) is a consortium of the major model organism databases and the Gene Ontology that is guided by the vision of facilitating exploration of related genes in human and well-studied model organisms by providing a highly integrated and comprehensive platform that enables researchers to leverage the extensive body of genetic and genomic studies in these organisms. Initiated in 2016, the Alliance is building a central portal (www.alliancegenome.org) for access to data for the primary model organisms along with gene ontology data and human data. All data types represented in the Alliance portal (e.g. genomic data and phenotype descriptions) have common data models and workflows for curation. All data are open and freely available via a variety of mechanisms. Long-term plans for the Alliance project include a focus on coverage of additional model organisms including those without dedicated curation communities, and the inclusion of new data types with a particular focus on providing data and tools for the non-model-organism researcher that support enhanced discovery about human health and disease. Here we review current progress and present immediate plans for this new bioinformatics resource.

The red maple and sugar maple (Acer rubrum and A. saccharum, respectively) contain acertannins (ginnalins and maplexins), galloylated derivatives of 1,5-anhydro- d -glucitol (1,5-AG, 1). These compounds have a variety of potential medicinal properties and we have shown that some of them promote the expression of ceramide synthase 3. We now report on the beneficial effects of ginnalin B, (6-O-galloyl-1,5-AG, 5), leading to acceleration of skin metabolism and reduction of the turnover time. Ginnalin B dose-dependently increased the relative amount of keratin 10, keratin 1, and filaggrin gene, with maximal increase of 1.7-, 2.9, and 5.2-fold at 100 μM, respectively. The validation study showed that it had superior capacity to induce multiple stages of keratinocyte differentiation and significantly elevated the immunostaining site of keratin 10 and filaggrin in a 3-dimensional cultured human skin model, by 1.2 and 2.8-fold, respectively. Furthermore, ginnalin B caused the arrest of proliferation at the G0/G1 phase but it did not induce apoptotic cell death in normal human keratinocytes. Molecular studies revealed that ginnalin B up-regulated the levels of NOTCH1 and a concomitant increase p21 expression. Ginnalin B, therefore, represents a new class of promising functional and medical cosmetic compound and it could contribute to the maintenance of homeostasis of the epidermis.

Background: Previous work had shown the ability of an aqueous leaf and stem extract of Cissus quandrangularis (300 mg of CQR, CQR-300) to improve components of metabolic syndrome (MS) in overweight individuals. Objective: This small pilot study aimed to confirm the efficacy of CQR-300 in reducing the percentage body fat measured using two different methods—bioelectrical impedance assay versus dual-energy X-ray absorptiometry (DEXA). Design: The study was an 8-week double-blind, placebo-controlled pilot trial on 67 individuals who were requested by a dietary counselor to maintain their normal exercise and dietary routines. Participants were randomly divided into two groups, placebo (32 participants) and the CQR-300 group (35 participants), and received 300 mg of corn starch or CQR-300 daily. Methods: Body fat was measured by bioelectrical impedance using a TANITA impedance meter and by DEXA, with blood samples taken at baseline and at 8 weeks for the measurement of lipid parameters. Results: After 8 weeks of treatment, participants of the placebo group showed a 1.05% decrease in body fat as determined by bioelectrical impedance analysis, but no difference using DEXA. In the same time period, the CQR-300 group had an 8.9% and 12.8% decreases in the body fat as measured by impedance and DEXA, respectively. These values were significantly (p

The use of plant-derived natural products for the treatment of tropical parasitic diseases often has ethnopharmacological origins. As such, plants grown in temperate regions remain largely untested for novel anti-parasitic activities. We describe here a screen of the PhytoQuest Phytopure library, a novel source comprising over 600 purified compounds from temperate zone plants, against in vitro culture systems for Plasmodium falciparum, Leishmania mexicana, Trypanosoma evansi and T. brucei. Initial screen revealed 6, 65, 15 and 18 compounds, respectively, that decreased each parasite’s growth by at least 50% at 1–2 µM concentration. These initial hits were validated in concentration-response assays against the parasite and the human HepG2 cell line, identifying hits with EC50 &lt, 1 μM and a selectivity index of &gt, 10. Two sesquiterpene glycosides were identified against P. falciparum, four sterols against L. mexicana, and five compounds of various scaffolds against T. brucei and T. evansi. An L. mexicana resistant line was generated for the sterol 700022, which was found to have cross-resistance to the anti-leishmanial drug miltefosine as well as to the other leishmanicidal sterols. This study highlights the potential of a temperate plant secondary metabolites as a novel source of natural products against tropical parasitic diseases.

We provide unique firm-level evidence of the relation between state ownership and stock liquidity. Using a broad sample of newly privatized firms (NPFs) from 53 countries over the period 1994–2014, our study identifies a non-monotonic association between state ownership and stock liquidity. The inverse U-shaped relation is consistent with trade-offs between costs and benefits of state ownership and suggests an optimal level of government shareholdings that maximizes stock liquidity of NPFs. We further identify that the inflection point from the cost/benefit trade-off is contingent upon characteristics of the nation's institutional environment., Highlights • We study how state ownership affects stock liquidity. • We identify a non-monotonic relation between state ownership and stock liquidity. • This relation is consistent with trade-offs between costs/benefits of state ownership. • The inflection point from this trade-off depends on the institutional environment.

Cucumbers have been anecdotally claimed to have anti-inflammatory activity for a long time, but the active principle was not identified. idoBR1, (2R,3R,4R,5S)-3,4,5-trihydroxypiperidine-2-carboxylic acid, is an iminosugar amino acid isolated from fruits of certain cucumbers, Cucumis sativus (Cucurbitaceae). It has no chromophore and analytically behaves like an amino acid making detection and identification difficult. It has anti-inflammatory activity reducing lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-α) in THP-1 cells and ex vivo human blood. It showed selective inhibition of human α-l-iduronidase and sialidases from both bacteria (Tannerella forsythia) and human THP-1 cells. idoBR1 and cucumber extract reduced the binding of hyaluronic acid (HA) to CD44 in LPS-stimulated THP-1 cells and may function as an anti-inflammatory agent by inhibiting induced sialidase involved in the production of functionally active HA adhesive CD44. Similar to the related iminosugars, idoBR1 is excreted unchanged in urine following consumption. Its importance in the diet should be further evaluated.