Sulindac sulfide reverses aberrant self-renewal of progenitor cells induced by the AML-associated fusion proteins PML/RARalpha and PLZF/RARalpha

Chromosomal translocations can lead to the formation of chimeric genes encoding fusion proteins such as PML/RARalpha, PLZF/RARalpha, and AML-1/ETO, which are able to induce and maintain acute myeloid leukemia (AML). One key mechanism in leukemogenesis is increased self renewal of leukemic stem cells via aberrant activation of the Wnt signaling pathway. Either X-RAR, PML/RARalpha and PLZF/RARalpha or AML-1/ETO activate Wnt signaling by upregulating gamma-catenin and beta-catenin. In a prospective study, a lower risk of leukemia was observed with aspirin use, which is consistent with numerous studies reporting an inverse association of aspirin with other cancers. Furthermore, a reduction in leukemia risk was associated with use of non-steroidal anti-inflammatory drug (NSAID), where the effects on AML risk was FAB subtype-specific. To better investigate whether NSAID treatment is effective, we used Sulindac Sulfide in X-RARalpha-positive progenitor cell models. Sulindac Sulfide (SSi) is a derivative of Sulindac, a NSAID known to inactivate Wnt signaling. We found that SSi downregulated both beta-catenin and gamma-catenin in X-RARalpha-expressing cells and reversed the leukemic phenotype by reducing stem cell capacity and increasing differentiation potential in X-RARalpha-positive HSCs. The data presented herein show that SSi inhibits the leukemic cell growth as well as hematopoietic progenitors cells (HPCs) expressing PML/RARalpha, and it indicates that Sulindac is a valid molecular therapeutic approach that should be further validated using in vivo leukemia models and in clinical settings

Tryggt ljus när mörkret faller på

36% av Malmös medborgare har i en undersökning uppgett att de känner sig otrygga när de går ensamma utomhus när det är mörkt. Ungefär hälften av dessa har även avstått från olika aktiviteter på grund av sin upplevda otrygghet. Trots att artificiell ljussättning ska göra det möjligt att leva sitt liv under dygnets alla timmar är det många människor, framförallt kvinnor, som känner sig otrygga när det blivit mörkt. Hur kommer det sig? Är inte ljussättningen av platserna tillfredställande nog? Denna studie undersöker sambandet mellan medveten ljusdesign och upplevd trygghet och vilken potential ljusdesign har för att skapa trygghet i staden efter mörkrets inbrott. Studien belyser även sambandet mellan trygghet och fysisk gestaltning samt undersöker trygghetsfrågan ur ett genusperspektiv. Syftet med studien är att bidra med kunskap om på vilket sätt ljusdesign, väl integrerad med den övriga gestaltningen, har betydelse för upplevelsen av våra urbana rum och den upplevda känslan av trygghet i staden. Ljus syns inte men är en förutsättning för vårt seende och vår uppfattningsförmåga. Våra upplevelser beror därmed på hur ljussättningen verkar i den fysiska miljön och hur den representeras för oss. Hur vi sedan uppfattar vår miljö beror på våra sinnen som skapar vår uppfattning, vilket i princip innebär att vi själva skapar vår miljö. Hur en skapar miljön beror på personliga erfarenheter hos betraktaren och därför är det svårt att enbart med hjälp av ljus skapa trygghet. Trygghet är en subjektiv företeelse som beskriver en tillfällig upplevelse och är ofta kopplad till särskilda platser eller sociala sammanhang, som i sin tur påverkar föreställningar om platsen. Johan Moritz, ansvarig för Malmö Stads ljussättning, menar att trygghetsupplevelser i sig inte beror på huruvida god ljussättningen är på en viss plats utan han ifrågasätter istället hur den byggda miljön är utformad. Den fysiska miljöns utformning menar han är den primära orsaken till att en människa känner sig otrygg snarare än ljuset i sig, då ljuset bara är en sekundär faktor vars uppgift är att få den fysiska miljön att synas på olika sätt. Trots att trygghet är individuellt finns ändå forskning som tagit fram en rad generella teorier som konkret går att applicera både i gestaltnings- och ljussättningprojekt. Överblickbarhet, goda siktlinjer, orienteringsmöjlighet och tillgänglighet är exempel på trygghetsskapande aspekter att ha i åtanke vid gestaltning. Social kontroll, folkmängd och skötsel är skiftande faktorer som också anses vara viktiga aspekter för att skapa trygga miljöer. Trygghet är alltså starkt kopplat till den visuella tillgängligheten. En rad slutsatser från en teoretisk bakgrundsstudie har tillämpats i framtagandet av ett ljussättningsförslag för en kommande stadsdelspark i Stångby, norr om Lund. Ljussättningsförslaget i denna studie har utgått ifrån ett befintligt gestaltningsförslag av platsen som syftar till att vara en attraktiv, upplevelserik och estetiskt tilltalande park i den växande stadsdelen. God ljussättning är en viktig del i gestaltningen för att både skapa upplevelsevärden och trygghet även under dygnets mörka timmar. Ljussättningsförslaget grundar sig i ett samspel mellan ljussättning och övrig gestaltning och med ambitionen att skapa trygghet. Min intention med förslaget har varit att beskriva behoven hos olika delområdena i parken och på vilket sätt ljussättningen kan uppnå dessa samtidigt som de trygghetsskapande ljussättningsprinciperna finns i åtanke.In a survey, 36% of Malmö’s citizens have stated that they do not feel safe when walking alone in public spaces when night falls. About half of these have also refrained from various activities because of the perceived insecurity. Despite the fact that artificial lighting would make it possible to live our lives during all hours of the day, many people, especially women, feel insecure when it´s dark. Why is that? Is not the public lighting satisfactory enough? This study examines the relationship between conscious lighting design and perceived safety and discusses how lighting design can contribute to spaces that are perceived as safe after dark. The study also highlights the connection between safety and physical design and examines the issue of perceived safety from a gender perspective. The purpose of this study is to contribute with knowledge of how light design, that is well integrated with the built environment, has significance for the experience of urban spaces and the perceived feeling of safety. Light is a prerequisition for our vision and our perception. Our experiences therefore depend on how the lighting works in the physical environment and how it is represented to us. How we in turn perceive our environment depends on our minds and senses that create our perception, which basically means that we create the environment ourselves. How we create the environment depends on personal experiences and it is therefore difficult to create safe places with only lighting. Perceived safety is a subjective term that describes a temporary experience and is often linked to specific places or social contexts, which in turn are influenced by notions of the place. Johan Moritz, responsible for the city lighting in Malmö, believes that perceived safety does not depend on whether a certain place is well lit, but instead he questions how the built environment is designed. He claims that the design of the physical environment is the primary reason to why a person does not feel safe, since light only is a secondary factor whose task is to make the physical environment visible. Despite the fact that perceived safety varies from individual to individual, research has produced a number of general theories that can be applied in design and lighting projects. Transparency, good line of sight, orientation opportunities and accessibility are examples of safetycreating principles to keep in mind when designing. Social control, population and management are changing factors that are also considered important aspects when creating safe environments. Perceived safety is thus strongly linked to the visual field of view. A number of conclusions from a theoretical study have been applied in the preparation of a lighting proposal for a future park in Stångby, north of the city of Lund. The lighting proposal in this study is based on an existing design proposal of the site, which aims to be an attractive, experiential and aesthetically pleasing park in the growing district. Good lighting is an important part of the design in order to create valuable and safe spaces even during the dark hours of the day. The lighting proposal is based on an interaction between lighting and the existing design and with the ambition to create safety. The intention with my proposal is to describe the needs of each area and in what way the lighting can achieve these, while keeping the principles of strategic lighting design in mind

The effects of resource availability on territorial behavior of the Ruby-throated Hummingbird (Archilochus colubris).

BirdsRuby-throated Hummingbirds (Archilochus colubris) often migrate to their summer breeding grounds, sometimes before their main food source, nectar from flowers, becomes available. On Douglas Lake at the University of Michigan Biological Station, Pellston, MI, we explored how resource availability affected aggressive behavior in hummingbirds. Eight lakeside sites had either a single or triple set of hummingbird feeders. We predicted that the richness of a resource site would determine the number of aggressive interactions initiated by males, with the more resource-rich sites experiencing higher frequencies of male-initiated territorial behavior. We also hypothesized that males would express more territorial behavior (chases and vocalizations) than females. We counted two types of territorial behavior in both males and females: chasings and vocalizations. Our results showed that more male aggression occurred at the resource-rich triple feeder sites, but there were more instances of female aggression than male aggression, especially at single feeder sites. Resource availability of a given site seems to be a determining factor affecting the distribution of each sex. Ihttp://deepblue.lib.umich.edu/bitstream/2027.42/109734/1/Biswas_Dollison_French_Roos_2014.pd

Pathogens stabilize or destabilize depending on host stage structure

A common assumption is that pathogens more readily destabilize their host populations, leading to an elevated risk of driving both the host and pathogen to extinction. This logic underlies many strategies in conservation biology and pest and disease management. Yet, the interplay between pathogens and population stability likely varies across contexts, depending on the environment and traits of both the hosts and pathogens. This context-dependence may be particularly important in natural consumer-host populations where size- and stage-structured competition for resources strongly modulates population stability. Few studies, however, have examined how the interplay between size and stage structure and infectious disease shapes the stability of host populations. Here, we extend previously developed size-dependent theory for consumer-resource interactions to examine how pathogens influence the stability of host populations across a range of contexts. Specifically, we integrate a size- and stage-structured consumer-resource model and a standard epidemiological model of a directly transmitted pathogen. The model reveals surprisingly rich dynamics, including sustained oscillations, multiple steady states, biomass overcompensation, and hydra effects. Moreover, these results highlight how the stage structure and density of host populations interact to either enhance or constrain disease outbreaks. Our results suggest that accounting for these cross-scale and bidirectional feedbacks can provide key insight into the structuring role of pathogens in natural ecosystems while also improving our ability to understand how interventions targeting one may impact the other

Children's physical activity and the preschool physical environment:The moderating role of gender

The physical environment in preschool, covering all indoor and outdoor equipment, and the surfaces of the preschool yard, may have a large potential for increasing children's physical activity (PA). However, it is less clear which specific physical environmental factors are associated with children's PA. Cross-sectional associations between the individual observed items (e.g. fixed and portable equipment, surfaces, terrain in the grounds) as well as composite scores for the PA equipment on the one hand, and children's PA, measured by accelerometers, on the other, were investigated in a sample of 3-6 year old children (N = 778) attending preschool in Finland. Having balance equipment and trampolines in group facilities, having balance equipment, gym mats and sticks in the gym and having skipping ropes, sand and mostly hilly terrain on the outdoor playground were associated with children's higher PA, regardless of gender. On the contrary, having gravel as the terrain in the playground and having a seesaw outdoors were associated with lower PA levels, regardless of gender. Four significant interactions with gender were found, but none of the environmental predictors remained significant in the post-hoc gender-stratified analyses. Variety in PA equipment and playground terrain may be beneficial for increasing children's PA in preschools. (C) 2018 Elsevier Inc. All rights reserved.</p

5-Lipoxygenase: Underappreciated Role of a Pro-Inflammatory Enzyme in Tumorigenesis

Leukotrienes constitute a group of bioactive lipids generated by the 5-lipoxygenase (5-LO) pathway. An increasing body of evidence supports an acute role for 5-LO products already during the earliest stages of pancreatic, prostate, and colorectal carcinogenesis. Several pieces of experimental data form the basis for this hypothesis and suggest a correlation between 5-LO expression and tumor cell viability. First, several independent studies documented an overexpression of 5-LO in primary tumor cells as well as in established cancer cell lines. Second, addition of 5-LO products to cultured tumor cells also led to increased cell proliferation and activation of anti-apoptotic signaling pathways. 5-LO antisense technology approaches demonstrated impaired tumor cell growth due to reduction of 5-LO expression. Lastly, pharmacological inhibition of 5-LO potently suppressed tumor cell growth by inducing cell cycle arrest and triggering cell death via the intrinsic apoptotic pathway. However, the documented strong cytotoxic off-target effects of 5-LO inhibitors, in combination with the relatively high concentrations of 5-LO products needed to achieve mitogenic effects in cell culture assays, raise concern over the assignment of the cause, and question the relationship between 5-LO products and tumorigenesis

Psychometric properties of the item-reduced version of the comprehensive general parenting questionnaire for caregivers of preschoolers in a Finnish context

Publisher Copyright: © 2022 Ray et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Introduction Many instruments for assessing general parenting have been reported as burdensome and are thus seldom used in studies exploring children’s energy balance-related behaviors or weight. This study evaluates the factorial structure of the item-reduced version of the Comprehensive General Parenting Questionnaire (CGPQ), which assesses five constructs of general parenting. Methods The study uses data from two cross-sectional studies: Study 1 in 2014 (n = 173) and Study 2 in 2015–16 (n = 805). Parents of children aged three to six answered the CGPQ; in Study 1 the 69-item version, and in Study 2 the 29-item version. The reduction was based on the results of the confirmatory factor analyses (CFA) in Study 1. In both datasets, internal consistency, as Cronbach’s alphas and intraclass correlations between the items of each construct, was tested. A combined assessment of the CFA and items response theory evaluated the construct validity and the item importance for the 29-item version, and a further the reduced 22-item version. Results In Study 1, the highest Cronbach’s alphas were shown for the five constructs in the 69-item version. A higher intraclass correlation was found between the constructs in the 69- and 29-item versions, than between the 69- and the 22-item version. However, a high concordance was found between the constructs in the 29- and 22-item versions in both Study 1 and in Study 2 (0.76–1.00). Testing the goodness-of-fit of the CFA models revealed that the 22-item model fulfilled all the criteria, showing that it had a better factorial structure than the 29-item model. Standard estimations ranged from 0.20 to 0.76 in the 22-item version. Conclusion The reduced 22- and 29-item versions of the 69-item CGPQ showed good model fit, the 22-item version the better of the two. These short versions can be used to assess general parenting without overburdening the respondents.Peer reviewe

Simple equations to predict concentric lower-body muscle power in older adults using the 30-second chair-rise test: a pilot study

Although muscle power is an important factor affecting independence in older adults, there is no inexpensive or convenient test to quantify power in this population. Therefore, this pilot study examined whether regression equations for evaluating muscle power in older adults could be derived from a simple chair-rise test. We collected data from a 30-second chair-rise test performed by fourteen older adults (76 ± 7.19 years). Average (AP) and peak (PP) power values were computed using data from force-platform and high-speed motion analyses. Using each participant’s body mass and the number of chair rises performed during the first 20 seconds of the 30-second trial, we developed multivariate linear regression equations to predict AP and PP. The values computed using these equations showed a significant linear correlation with the values derived from our force-platform and high-speed motion analyses (AP: R = 0.89; PP: R = 0.90; P < 0.01). Our results indicate that lower-body muscle power in fit older adults can be accurately evaluated using the data from the initial 20 seconds of a simple 30-second chair-rise test, which requires no special equipment, preparation, or setting

A Standardized Workflow Based on the STAVIRO Unbaited Underwater Video System for Monitoring Fish and Habitat Essential Biodiversity Variables in Coastal Areas

Essential Biodiversity Variables (EBV) related to benthic habitats and high trophic levels such as fish communities must be measured at fine scale but monitored and assessed at spatial scales that are relevant for policy and management actions. Local scales are important for assessing anthropogenic impacts, and conservation-related and fisheries management actions, while reporting on the conservation status of biodiversity to formulate national and international policies requires much broader scales. Measurements must account for the fact that coastal habitats and fish communities are heterogeneously distributed locally and at larger scales. Assessments based on in situ monitoring generally suffer from poor spatial replication and limited geographical coverage, which is challenging for area-wide assessments. Requirements for appropriate monitoring comprise cost-efficient and standardized observation protocols and data formats, spatially scalable and versatile data workflows, data that comply with the FAIR (Findable, Accessible, Interoperable, and Reusable) principles, while minimizing the environmental impact of measurements. This paper describes a standardized workflow based on remote underwater video that aims to assess fishes (at species and community levels) and habitat-related EBVs in coastal areas. This panoramic unbaited video technique was developed in 2007 to survey both fishes and benthic habitats in a cost-efficient manner, and with minimal effect on biodiversity. It can be deployed in areas where low underwater visibility is not a permanent or major limitation. The technique was consolidated and standardized and has been successfully used in varied settings over the last 12 years. We operationalized the EBV workflow by documenting the field protocol, survey design, image post-processing, EBV production and data curation. Applications of the workflow are illustrated here based on some 4,500 observations (fishes and benthic habitats) in the Pacific, Indian and Atlantic Oceans, and Mediterranean Sea. The STAVIRO’s proven track-record of utility and cost-effectiveness indicates that it should be considered by other researchers for future applications.publishedVersio

Train the Trainer for general practice trainer - a report of the pilot within the programme Verbundweiterbildungplus

Background: Since 2008 the Verbundweiterbildungplus programme of the Competence Centre General Practice Baden-Wuerttemberg offers continual improvement with regards to content and structure of general practice training. The programme uses the didactical concept of the CanMEDs competencies, which were developed in Canada, as a postgraduate medical training framework. Train the trainer (TTT)-programmes are an additional important element of these contentual optimisations of postgraduate training. Within this article we describe the conception and evaluation of the first TTT-workshop within the programme Verbundweiterbildungplus