19 research outputs found

    Protein kinase A controls yeast growth in visible light

    Get PDF
    Background: A wide variety of photosynthetic and non-photosynthetic species sense and respond to light, having developed protective mechanisms to adapt to damaging effects on DNA and proteins. While the biology of UV light-induced damage has been well studied, cellular responses to stress from visible light (400–700 nm) remain poorly understood despite being a regular part of the life cycle of many organisms. Here, we developed a high-throughput method for measuring growth under visible light stress and used it to screen for light sensitivity in the yeast gene deletion collection. Results: We found genes involved in HOG pathway signaling, RNA polymerase II transcription, translation, diphthamide modifications of the translational elongation factor eEF2, and the oxidative stress response to be required for light resistance. Reduced nuclear localization of the transcription factor Msn2 and lower glycogen accumulation indicated higher protein kinase A (cAMP-dependent protein kinase, PKA) activity in many light-sensitive gene deletion strains. We therefore used an ectopic fluorescent PKA reporter and mutants with constitutively altered PKA activity to show that repression of PKA is essential for resistance to visible light. Conclusion: We conclude that yeast photobiology is multifaceted and that protein kinase A plays a key role in the ability of cells to grow upon visible light exposure. We propose that visible light impacts on the biology and evolution of many non-photosynthetic organisms and have practical implications for how organisms are studied in the laboratory, with or without illumination

    Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

    Get PDF
    BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

    Trafikverket och kunden: Kundorientering som stöd i Trafikverkets uppdrag?

    No full text
    Under 2015 har Institutet för personal- och företagsutveckling, IPF, på uppdrag av Trafikverket, genomfört en förstudie som behandlar kund- och intressentbegreppets betydelse för den interna verksamheten. I studien, liksom i tidigare genomförda studier, framkommer att termen ”kund” ofta uppfattas som ett hinder i verksamheten, bland annat beroende på var man befinner sig i organisationen och vilka externa intressenter man möter i sitt dagliga arbete. Detta hinder löses inte med hjälp av ett tydligare definierat kundbegrepp, utan istället handlar det om att skapa ett gemensamt förhållningssätt som präglas av en gemensam föreställning om hur Trafikverket kan skapa värde för sina mottagare.Kund och intressentbegreppets betydelse för den interna verksamhete

    High-throughput Growth Measurements of Yeast Exposed to Visible Light

    No full text
    Light is a double-edged sword: it is essential for life on the planet but also causes cellular damage and death. Consequently, organisms have evolved systems not only for harvesting and converting light energy into chemical energy but also for countering its toxic effects. Despite the omnipresence and importance of such light-dependent effects, there are very few unbiased genetic screens, if any, investigating the mechanistic consequences that visible light has on cells. Baker’s yeast, Saccharomyces cerevisiae, is one of the best annotated organisms thanks to several easily available mutant collections and its amenability to high-throughput genetic screening. However, until recently this yeast was thought to lack receptors for visible light, therefore its response to visible light was poorly understood. Nevertheless, a couple of years ago it was discovered that yeast senses light via a novel and unconventional pathway involving a peroxisomal oxidase, hydrogen peroxide, and a particular type of antioxidant protein, called peroxiredoxin. Here, we describe in detail a protocol for scoring yeast genes involved in the resistance to visible light (400-700 nm) on a genome-wide scale. Because cells in dense cultures shield each other from light exposure, resulting in apparent light resistance, our method involves adaptations to reduce inoculum size under conditions amenable to high-throughput screens, to properly be able to identify light-sensitive mutants. We also describe how to measure growth in the presence of light, including two follow-up validation tests. In this way, this method makes it possible to score light-sensitivity on a genome-wide scale with high confidence

    Treating perfectionism using internet-based cognitive behavior therapy : A study protocol for a randomized controlled trial comparing two types of treatment

    Get PDF
    Perfectionism is characterized by setting high standards and striving for achievement, sometimes at the expense of social relationships and wellbeing. Despite sometimes being viewed as a positive feature by others, people with perfectionism tend to be overly concerned about their performance and how they are being perceived by people around them. This tends to create inflexible standards, cognitive biases, and performance-related behaviors that maintain a belief that self-worth is linked to accomplishments. Cognitive behavior therapy has been shown to be a viable treatment for perfectionism, both in terms of reducing levels of perfectionism and improving psychiatric symptoms. Furthermore, a number of recent studies indicate that it can be successfully delivered via the Internet, both with regular support and guidance on demand from a therapist. In the present study protocol, a clinical trial for perfectionism is described and outlined. In total, 128 participants will be recruited and randomized to either a treatment that has already been demonstrated to have many benefits, Internet-based Cognitive Behavior Therapy for perfectionism (iCBT-P), or an active comparison condition, Internet-based Unified Protocol (iUP), targeting the emotions underlying depression and anxiety disorders. The results will be investigated with regard to self-reported outcomes of perfectionism, psychiatric symptoms, self-compassion, and quality of life, at post-treatment and at six- and 12-month follow-up. Both iCBT-P and iUP are expected to have a positive impact, but the difference between the two conditions in terms of their specific effects and adherence are currently unknown and will be explored. The clinical trial is believed to lead to a better understanding of how perfectionism can be treated and the specificity of different treatments

    Treating perfectionism via the Internet: a randomized controlled trial comparing cognitive behavior therapy to unified protocol

    No full text
    Perfectionism can be problematic when your self-worth is dependent on achievements and leads to inflexible standards, cognitive biases, and rigid behaviors. Cognitive behavior therapy for perfectionism is shown to be effective, including for targeting psychiatric symptoms and when delivered via the Internet (iCBT-P). However, few studies have compared it to an active comparator. The current study randomly assigned 138 participants seeking help for perfectionism to iCBT-P or Internet-based Unified Protocol (iUP). Both treatments provided guidance on demand from a therapist and were eight weeks in duration. The results indicated large within-group effects of Cohen’s d 2.03 (iCBT) and 2.51 (iUP) on the Clinical Perfectionism Questionnaire at post-treatment, and maintained effects at 6- and 12-month follow-up, but no between-group difference (β = 0.02, SE = 1.04, p =.98). Secondary outcomes of depression, anxiety, quality of life, self-compassion, procrastination, and stress ranged from small to large, with no differences between the conditions. Both treatments were deemed credible, relevant, of high quality, and well-adhered by the participants. Further research needs to be conducted, but the findings could indicate a lack of specificity, perhaps suggesting there is no need to differentiate between different treatments that are transdiagnostic in nature.Validerad;2024;Nivå 2;2024-03-25 (hanlid);Full text license: CC BY 4.0</p

    Prediction of symptomatic improvement after exposure-based treatment for irritable bowel syndrome

    No full text
    Background: Several studies show that psychological treatments relieve symptoms for patients suffering from irritable bowel syndrome (IBS). However, there are no consistent findings that show what patient characteristics make a psychological treatment more or less likely to result in improvement. We have previously conducted a study of a newly developed internet-delivered cognitive behavioral therapy (ICBT) that emphasized exposure to IBS symptoms and IBS-related situations and reduced symptom-related avoidance. The study showed that the treatment led to improvement in IBS symptoms compared to a waiting list and that treatment gains were maintained over a 15-18 month follow-up period. The aim of the present study was to investigate several possible predictors of short-and long-term treatment outcome in terms of symptom improvement, based on data collected in the previously conducted treatment trial. less thanbrgreater than less thanbrgreater thanMethods: Demographics, comorbid psychological distress, IBS-related fear and avoidance behaviors, and IBS-related disability were investigated as predictors of treatment outcome in the sample consisting of 79 participants diagnosed with IBS who had undergone 10 weeks of ICBT. Predictors that were significantly correlated with symptom levels at post-treatment and follow-up were entered into multiple regression analyses that controlled for pre-treatment symptom levels. less thanbrgreater than less thanbrgreater thanResults: There were measures within each domain, i.e., comorbid psychological distress, IBS-related fear and avoidance behaviors, and IBS-related disability, with the exception of demographic data, that were correlated with the symptom levels at post-treatment and follow-up. However, when these were entered into a multiple regression analyses that controlled for pre-treatment levels, none remained a significant predictor of the post-treatment and follow-up symptomatic status. less thanbrgreater than less thanbrgreater thanConclusions: The study did not find any individual characteristics that made patients more or less likely to respond to the exposure-based ICBT. The finding that comorbid psychological distress did not predict outcome is in accordance with previous studies. Reliable predictors for response to any type of psychological treatment for IBS remain to be established

    Prediction of symptomatic improvement after exposure-based treatment for irritable bowel syndrome

    No full text
    Background: Several studies show that psychological treatments relieve symptoms for patients suffering from irritable bowel syndrome (IBS). However, there are no consistent findings that show what patient characteristics make a psychological treatment more or less likely to result in improvement. We have previously conducted a study of a newly developed internet-delivered cognitive behavioral therapy (ICBT) that emphasized exposure to IBS symptoms and IBS-related situations and reduced symptom-related avoidance. The study showed that the treatment led to improvement in IBS symptoms compared to a waiting list and that treatment gains were maintained over a 15-18 month follow-up period. The aim of the present study was to investigate several possible predictors of short-and long-term treatment outcome in terms of symptom improvement, based on data collected in the previously conducted treatment trial. Methods: Demographics, comorbid psychological distress, IBS-related fear and avoidance behaviors, and IBS-related disability were investigated as predictors of treatment outcome in the sample consisting of 79 participants diagnosed with IBS who had undergone 10 weeks of ICBT. Predictors that were significantly correlated with symptom levels at post-treatment and follow-up were entered into multiple regression analyses that controlled for pre-treatment symptom levels. Results: There were measures within each domain, i.e., comorbid psychological distress, IBS-related fear and avoidance behaviors, and IBS-related disability, with the exception of demographic data, that were correlated with the symptom levels at post-treatment and follow-up. However, when these were entered into a multiple regression analyses that controlled for pre-treatment levels, none remained a significant predictor of the post-treatment and follow-up symptomatic status. Conclusions: The study did not find any individual characteristics that made patients more or less likely to respond to the exposure-based ICBT. The finding that comorbid psychological distress did not predict outcome is in accordance with previous studies. Reliable predictors for response to any type of psychological treatment for IBS remain to be established

    Prediction of symptomatic improvement after exposure-based treatment for irritable bowel syndrome

    No full text
    Background: Several studies show that psychological treatments relieve symptoms for patients suffering from irritable bowel syndrome (IBS). However, there are no consistent findings that show what patient characteristics make a psychological treatment more or less likely to result in improvement. We have previously conducted a study of a newly developed internet-delivered cognitive behavioral therapy (ICBT) that emphasized exposure to IBS symptoms and IBS-related situations and reduced symptom-related avoidance. The study showed that the treatment led to improvement in IBS symptoms compared to a waiting list and that treatment gains were maintained over a 15-18 month follow-up period. The aim of the present study was to investigate several possible predictors of short-and long-term treatment outcome in terms of symptom improvement, based on data collected in the previously conducted treatment trial. less thanbrgreater than less thanbrgreater thanMethods: Demographics, comorbid psychological distress, IBS-related fear and avoidance behaviors, and IBS-related disability were investigated as predictors of treatment outcome in the sample consisting of 79 participants diagnosed with IBS who had undergone 10 weeks of ICBT. Predictors that were significantly correlated with symptom levels at post-treatment and follow-up were entered into multiple regression analyses that controlled for pre-treatment symptom levels. less thanbrgreater than less thanbrgreater thanResults: There were measures within each domain, i.e., comorbid psychological distress, IBS-related fear and avoidance behaviors, and IBS-related disability, with the exception of demographic data, that were correlated with the symptom levels at post-treatment and follow-up. However, when these were entered into a multiple regression analyses that controlled for pre-treatment levels, none remained a significant predictor of the post-treatment and follow-up symptomatic status. less thanbrgreater than less thanbrgreater thanConclusions: The study did not find any individual characteristics that made patients more or less likely to respond to the exposure-based ICBT. The finding that comorbid psychological distress did not predict outcome is in accordance with previous studies. Reliable predictors for response to any type of psychological treatment for IBS remain to be established

    Communication and reasons for its formation in artificial environments

    Get PDF
    Darbā tiek pētīta pašreizējā situācija mākslīgu aģentu radīšanai un to apmācīšanai efektīvi rīkoties mākslīgās vidēs, kurās ir iespējama komunikācija starp aģentiem. Tiek apskatītas populāras vides aģentu apmācībai un to snieguma novērtēšanai, tiek apzinātas vides, kurās var veikt aģentu apmācību komunicēt. Darbā aplūkoti populāri mašīnmācīšanās algoritmu aģentu apmācībai efektīvi rīkoties dažādās vidēs. Tiek īsumā pārspriests, kā nodrošināt vienkāršu komunikāciju un atmiņu aģentu arhitektūrā, kā to apmācīt. Tiek apzināti neseni komunikācijas pētījumi ar mākslīgi radītiem aģentiem un noskaidroti dažādi kvantitatīvi un kvalitatīvi rādītāji, lai varētu konstatēt lietderīgas, nelietderīgas komunikācijas rašanos. Darbā tiek reproducēts 2019. gada pavasara raksta ”On the Pitfalls of Measuring Emergent Communication”[15] rezultāts, kurā tiek novērota nelietderīgas komunikācijas rašanās aģenta arhitektūras dēļ. Darbā tiek veikti papildus eksperimenti ar izmaiņām vidē, aģentu arhitektūrā uz dažādām vides, aģentu konfigurācijām. Tiek veikta izpēte rakstā norādītājā turpmākajā pētījumu virzienā, vai, komunikācijai piemērojot papildus maksu, aģentu starpā veidojas nelietderīga komunikācija.This work examines the current situation in artificial agent creation and in their training to effectively act in artificially created environments with communication opportunities between agents. The author looks into popular environments which are used for training and evaluating agents, specifically into the ones where communication is possible. The author describes popular machine learning algorithms that are used for training agents to effectively act in the environment and how to implement a simple communication channel between agents. The work reviews recent papers about research in artificially created agent communication. The author reviews different metrics to measure the presence of usable and nonusable communication and reproduces experiment in the paper ”On the pitfalls of Measuring Emergent Communication”[15], which observed emerging of nonusable communication caused by the architecture of agent. Experiments are reproduced with a couple of changes in communication and architecture of both agents. The author does further research to find out if applying communication cost reduces the amount of nonusable communication
    corecore