Cytokinin antagonists and antibiotics related to nalidixic acid : effects on Phaseolus and Nicotiana callus tissues

The effects of five cytokinin antagonists on the growth of cytokinin-autonomous lines of Phaseolus lunatus cv. Kingston, Phaseolus vulgaris cv. Great Northern, and Nicotiana tabacum cv. Wisconsin 38 callus tissues have been compared. The antagonists tested included four N⁴-substituted 4-amino-2-methylthiopyrrolo[2,3-d]pyrimidines bearing the following N⁴ side chains, 4-n-pentyl- (ms²pnN⁴Prp), 4-n-hexyl- (ms²HxN⁴Prp), 4-cyclopentyl- (ms²cPnN⁴prp), and 4-cyclohexyl- (ms²cHxN⁴prp) and one 7- amino-3-methylpyrazolo[4,3-d]pyrimidine with the N⁷ side chain, 7-n-pentyl- (m³pnN⁷pzp). All antagonists tested inhibited Nicotiana and Phaseolus callus tissues growth. Inhibition of the Phaseolus callus tissues required higher antagonist concentrations than required to inhibit Nicotiana callus tissue. With all three tissues, the most potent of the antagonists was m³PnN⁷Pzp. However, the antagonist structure/activity relationships observed in tests with the pyrrolopyrimidine derivatives were not identical for all three tissues. The inhibitory effects of ms²PnN⁴Prp and m³PnN⁷Pzp on the growth of cytokinin-autonomous N. tabacum and P. lunatus callus tissues were partially reversed by the addition of exogenous N⁶-(Δ²-isopentenyl)adenine (i⁶Ade), as evidenced by the effect of i⁶Ade in increasing the concentrations of antagonists required to produce 50% inhibition of callus growth (I₅₀ values). The interactions of cytokinin antagonists and exogenous cytokinins in the cytokinin-autonomous Nicotiana callus tissue appear to be more complex than in the corresponding cytokinin-dependent Nicotiana callus tissue. The exogenously supplied cytokinins are themselves inhibitory to the growth of the cytokinin-autonomous line of Nicotiana callus tissue. Nalidixic acid, a compound reported to inhibit mammalian cell cultures in a manner reversible by cytokinin treatment (Quesney-Huneeus et al., (1980), Proc. Natl. Acad. Sci. USA., 77 5842.), was tested along with the related antibiotics, oxolinic acid and novobiocin, for effects on the growth of cytokinin-autonomous and cytokinin-dependent P. lunatus cv. Kingston and N. tabacum cv. Wisconsin 38 callus tissues. This investigation was undertaken to determine whether interactions of cytokinins and nalidixic acid similar to those observed in mammalian cell cultures could be detected in plant cell cultures. All three antibiotics inhibited growth of the callus tissues. The Nicotiana callus tissues were more sensitive than the Phaseolus tissues. In all tissues, oxolinic acid was the most effective of the antibiotics in inhibiting callus growth, and novobiocin was the least effective of the three antibiotics. The inhibitory effects of nalidixic acid and oxolinic acid on cytokinin-dependent Phaseolus callus tissue appeared to be partially alleviated by exogenous i⁶Ade treatment as evidenced by the effect of i⁶Ade in increasing the I₅₀ values for nalidixic acid and oxolinic acid. By this criterion, the inhibitory effects of novobiocin on callus growth did not appear to be reversed by treatment with exogenous i⁶Ade. Interestingly, in tests with the cytokinin-autonomous Nicotiana callus tissue, a low concentration (0.01 μM) of nalidixic acid appeared to reverse the inhibitory effects of high i⁶Ade concentrations. A similar effect with this tissue was observed in tests of the antagonist m³PnN⁷Pzp. The results of this study raise the possibility that some part of the effects of nalidixic acid and oxolinic acid on plant tissues may be due to effects on processes specifically involving cytokinin metabolism or function. However, in no case was i⁶Ade able to completely reverse the effects of antibiotic treatment

Extending Dynamic Queries to Handle Uncertain Data.

Dynamic querying is a technique which has been used successfully to enable novice users to gain access to and insight into data in databases. Some multimedia archives (such as archives of African art) contain data which have vague locations in time and space, that is, although there is some idea of when and where the entity originated, the precise information is unknown. This uncertainty creates problems with the display and querying of the data and so the data is generally not accessible to novice users. In this study we extend dynamic querying techniques to work with African art data with uncertain origins in time and space. We present methods for storing, visualising and querying such uncertain data within the framework of dynamic querying. Results of user tests indicate that our approach was clear to users and that users could successfully perform simple queries using the visual query tools. A similar approach of extending dynamic querying techniques could apply to other domains with any one-dimensional attribute data with probabilistic uncertainty. In this way we show how it is possible for novice users to query large databases with complex uncertain attributes

Visual Query Tools for Uncertain Spatio-Temporal Data

Some multimedia archives contain data which have vague locations in time and space. By this we mean that, although there is some idea of when and where the entity is located, the precise information is unknown. In this paper, we present a novel approach to displaying and querying such uncertain data. We use the concepts of dynamic queries, add to this a 2D query tool for performing spatial queries and enable Boolean combinations of queries. We have implemented these ideas in a pilot system for querying African artwork. In this way, we show how it is possible for novice users to easily query large multimedia archives with complex uncertain attributes

Using Digital Technology to Access And Store African Art

In this paper, we describe the challenges in creating, and providing access to, a database of African cultural artifacts. The submission is targeted at the section 2 in the consortium – how HCI research is being used to support the African Renaissance

Delay Discounting as a Transdiagnostic Process in Psychiatric Disorders: A Meta-analysis

Importance Delay discounting is a behavioral economic index of impulsive preferences for smaller-immediate or larger-delayed rewards that is argued to be a transdiagnostic process across health conditions. Studies suggest some psychiatric disorders are associated with differences in discounting compared with controls, but null findings have also been reported. Objective To conduct a meta-analysis of the published literature on delay discounting in people with psychiatric disorders. Data Sources PubMed, MEDLINE, PsycInfo, Embase, and Web of Science databases were searched through December 10, 2018. The psychiatric keywords used were based on DSM-IV or DSM-5 diagnostic categories. Collected data were analyzed from December 10, 2018, through June 1, 2019. Study Selection Following a preregistered Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol, 2 independent raters reviewed titles, abstracts, and full-text articles. English-language articles comparing monetary delay discounting between participants with psychiatric disorders and controls were included. Data Extraction and Synthesis Hedges g effect sizes were computed and random-effects models were used for all analyses. Heterogeneity statistics, one-study-removed analyses, and publication bias indices were also examined. Main Outcomes and Measures Categorical comparisons of delay discounting between a psychiatric group and a control group. Results The sample included 57 effect sizes from 43 studies across 8 diagnostic categories. Significantly steeper discounting for individuals with a psychiatric disorder compared with controls was observed for major depressive disorder (Hedges g = 0.37; P = .002; k = 7), schizophrenia (Hedges g = 0.46; P = .004; k = 12), borderline personality disorder (Hedges g = 0.60; P < .001; k = 8), bipolar disorder (Hedges g = 0.68; P < .001; k = 4), bulimia nervosa (Hedges g = 0.41; P = .001; k = 4), and binge-eating disorder (Hedges g = 0.34; P = .001; k = 7). In contrast, anorexia nervosa exhibited statistically significantly shallower discounting (Hedges g = –0.30; P < .001; k = 10). Modest evidence of publication bias was indicated by a statistically significant Egger test for schizophrenia and at the aggregate level across studies. Conclusions and Relevance Results of this study appear to provide empirical support for delay discounting as a transdiagnostic process across most of the psychiatric disorders examined; the literature search also revealed limited studies in some disorders, notably posttraumatic stress disorder, which is a priority area for research

Interfaces to Digital Collections of African Art

This paper describes some of the issues in creating a digital collection of African art. We start by investigating the problems of uncertainty in the data relating to this art and propose a database model to cope with this uncertainty. We then investigate interfaces to query such a collection and discuss how best to display the results of the query in a virtual gallery

Interferon lambda is required for interferon gamma-expressing NK cell responses but does not afford antiviral protection during acute and persistent murine cytomegalovirus infection

Interferon lambda (IFNλ) is a group of cytokines that belong to the IL-10 family. They exhibit antiviral activities against certain viruses during infection of the liver and mucosal tissues. Here we report that IFNλ restricts in vitro replication of the β-herpesvirus murine cytomegalovirus (mCMV). However, IFNλR1-deficient (Ifnλr1-/-) mice were not preferentially susceptible to mCMV infection in vivo during acute infection after systemic or mucosal challenge, or during virus persistence in the mucosa. Instead, our studies revealed that IFNλ influences NK cell responses during mCMV infection. Ifnλr1-/- mice exhibited defective development of conventional interferon-gamma (IFNγ)-expressing NK cells in the spleen during mCMV infection whereas accumulation of granzyme B-expressing NK cells was unaltered. In vitro, development of splenic IFNγ+ NK cells following stimulation with IL-12 or, to a lesser extent, IL-18 was abrogated by IFNλR1-deficiency. Thus, IFNλ regulates NK cell responses during mCMV infection and restricts virus replication in vitro but is redundant in the control of acute and persistent mCMV replication within mucosal and non-mucosal tissues

Influences on the adoption of patient safety innovation in primary care: a qualitative exploration of staff perspectives

Background: Primary care is changing rapidly to meet the needs of an ageing and chronically ill population. New ways of working are called for yet the introduction of innovative service interventions is complicated by organisational challenges arising from its scale and diversity and the growing complexity of patients and their care. One such intervention is the multi-strand, single platform, Patient Safety Toolkit developed to help practices provide safer care in this dynamic and pressured environment where the likelihood of adverse incidents is increasing. Here we describe the attitudes of staff toward these tools and how their implementation was shaped by a number of contextual factors specific to each practice.Methods: The Patient Safety Toolkit comprised six tools; a system of rapid note review, an online staff survey, a patient safety questionnaire, prescribing safety indicators, a medicines reconciliation tool, and a safe systems checklist. We implemented these tools at practices across the Midlands, the North West, and the South Coast of England and conducted semi-structured interviews to determine staff perspectives on their effectiveness and applicability.Results: The Toolkit was used in 46 practices and a total of 39 follow-up interviews were conducted. Three key influences emerged on the implementation of the Toolkit these related to their ease of use and the novelty of the information they provide; whether their implementation required additional staff training or practice resource; and finally factors specific to the practice’s local environment such as overlapping initiatives orchestrated by their CCG.Conclusions: The concept of a balanced toolkit to address a range of safety issues proved popular. A number of barriers and facilitators emerged in particular those tools that provided relevant information with a minimum impact on practice resource were favoured. Individual practice circumstances also played a role. Practices with IT aware staff were at an advantage and those previously utilising patient safety initiatives were less likely to adopt additional tools with overlapping outputs. By acknowledging these influences we can better interpret reaction to and adoption of individual elements of the toolkit and optimise future implementation

A patient safety toolkit for family practices

Objectives: Major gaps remain in our understanding of primary care patient safety. We describe a toolkit for measuring patient safety in family practices. Methods: Six tools were used in 46 practices. These tools were: NHS Education for Scotland Trigger Tool, NHS Education for Scotland Medicines Reconciliation Tool, Primary Care Safequest, Prescribing Safety Indicators, PREOS-PC, and Concise Safe Systems Checklist. Results: PC-Safequest showed that most practices had a well-developed safety climate. However, the Trigger Tool revealed that a quarter of events identified were associated with moderate or substantial harm, with a third originating in primary care and avoidable. Although medicines reconciliation was undertaken within 2 days in >70% of cases, necessary discussions with a patient/carer did not always occur. The prescribing safety indicators identified 1,435 instances of potentially hazardous prescribing or lack of recommended monitoring (from 92,649 patients). The Concise Safe Systems Checklist found that 25% of staff thought their practice provided inadequate follow-up for vulnerable patients discharged from hospital and inadequate monitoring of non-collection of prescriptions. Most patients had a positive perception of the safety of their practice although 45% identified at least one safety problem in the past year. Conclusions: Patient safety is complex and multidimensional. The Patient Safety Toolkit is easy to use and hosted on a single platform with a collection of tools generating practical and actionable information. It enables family practices to identify safety deficits that they can review and change procedures to improve their patient safety across a key sets of patient safety issues