Control of Flowering and Cell Fate by LIF2, an RNA Binding Partner of the Polycomb Complex Component LHP1

Polycomb Repressive Complexes (PRC) modulate the epigenetic status of key cell fate and developmental regulators in eukaryotes. The chromo domain protein LIKE HETEROCHROMATIN PROTEIN1 (LHP1) is a subunit of a plant PRC1-like complex in Arabidopsis thaliana and recognizes histone H3 lysine 27 trimethylation, a silencing epigenetic mark deposited by the PRC2 complex. We have identified and studied an LHP1-Interacting Factor2 (LIF2). LIF2 protein has RNA recognition motifs and belongs to the large hnRNP protein family, which is involved in RNA processing. LIF2 interacts in vivo, in the cell nucleus, with the LHP1 chromo shadow domain. Expression of LIF2 was detected predominantly in vascular and meristematic tissues. Loss-of-function of LIF2 modifies flowering time, floral developmental homeostasis and gynoecium growth determination. lif2 ovaries have indeterminate growth and produce ectopic inflorescences with severely affected flowers showing proliferation of ectopic stigmatic papillae and ovules in short-day conditions. To look at how LIF2 acts relative to LHP1, we conducted transcriptome analyses in lif2 and lhp1 and identified a common set of deregulated genes, which showed significant enrichment in stress-response genes. By comparing expression of LHP1 targets in lif2, lhp1 and lif2 lhp1 mutants we showed that LIF2 can either antagonize or act with LHP1. Interestingly, repression of the FLC floral transcriptional regulator in lif2 mutant is accompanied by an increase in H3K27 trimethylation at the locus, without any change in LHP1 binding, suggesting that LHP1 is targeted independently from LIF2 and that LHP1 binding does not strictly correlate with gene expression. LIF2, involved in cell identity and cell fate decision, may modulate the activity of LHP1 at specific loci, during specific developmental windows or in response to environmental cues that control cell fate determination. These results highlight a novel link between plant RNA processing and Polycomb regulation

Emotional well-being and predictors of birth-anxiety, self-efficacy, and psychosocial adaptation in healthy pregnant women

BACKGROUND: A broad body of studies have shown that emotional well-being during pregnancy influences birth outcome and postpartum mood state, but few longitudinal studies have examined the extent of changes of emotional well-being during late pregnancy. Furthermore, up to now it has remained unclear which factors are predictive for emotional well-being during pregnancy. This prospective longitudinal study has two main aims. First of all, possibly occurring changes of birth anxiety, self-efficacy for labor and delivery, and psychosocial adaptation to pregnancy in primiparous healthy women during the final trimenon will be described. Second, predictors of these assessed constructs during the final trimenon as well as the extent of these constructs as predictors for the psychological status postpartum will be shown. METHODS: A prospective longitudinal study was conducted with 61 pregnant women recruited from childbirth classes. RESULTS: The results showed significant changes in emotional well-being--measured by birth anxiety, self-efficacy for labor and delivery, and psychosocial adaptation to pregnancy--during the final trimenon: the women were more confident in their ability to cope with labor and delivery. Birth anxiety did not change significantly during the final trimenon. Regression analyses revealed different psychosocial predictor variables for emotional well-being during late pregnancy. The predictive factor for an unfavorable psychological status postpartum was birth anxiety. CONCLUSIONS: The results of this study suggest that the importance of discovering psychosocial problems of pregnant woman early in pregnancy could be imperative in preventing psychosocial problems later in pregnancy as well as postpartum

Development of a protocol to study the bactericidal activity of metal anatase (TiO 2 )

Metal anatase (TiO 2 ) is an industrially important compound, currently used in a variety of applications as a white pigment. Anatase has also been shown to kill bacteria in the presence of blue light. This property has been exploited in the purification of water. However, the basis of cell killing has not been confirmed and remains under investigation. To study the proposed model of killing by reactive oxygen species, a suitable protocol must be designed. Sample volume, culture concentration, method of anatase plate sterilization, and light intensity are important variables that influence the degree of killing. Previous experiments focused on small volume sizes, however in this study larger sample volumes were used to investigate the feasibility of large scale sterilization procedures. Due to difficulties in development of a functional protocol, killing in large volume samples could not be assessed, yet remains a future pursuit. Killing in a 150µl bubble was enhanced when anatase plates were sterilized by boiling in water compared to sterilization with acetone. Killing was also enhanced when light intensity was increased. Although these modifications resulted in enhanced cell killing, it was still substantially less than previously reported. As the activity of these anatase plates was greater in experiments conducted five years ago, the effect of plate age and storage on the long-term activity of anatase should be investigated. The metal anatase (TiO 2 ) is currently used in interior paints, plastic filling, paper filling and highway marking paints as a white pigment. Interestingly, it may also play a role as a disinfectant. The first report of photocatalytic disinfection was the work of Matsunaga and coworkers in 1985 (3). Over the last 25 years, its usefulness in the removal of organic matter from air and water has been explored (1, 2, 4). However, the basis of cell killing has not been confirmed and remains under investigation. Anatase has photocatalytic activity that through a series of chemical steps produces reactive oxygen species (including the hydroxyl radical) that can cause fatal damage to microorganisms. Light is required to initiate this process by the following reaction: TiO 2 + Blue Light → TiO 2 -+ OH • (1). Initially, this study was most interested in investigating the relationship between reactive oxygen species and cell death, a relationship that has yet to be confirmed and characterized. It was thought that a correlation between the concentration of reactive oxygen species and the amount of cell death might be observed and lend support to this model of cell killing. However, in preparation for this proposed experiment, the authors found that the set-up and design required multiple tests and modifications, and thus the study became one of experimental design. The effects of volume, concentration of bacterial sample, method of sterilization of the anatase plates, and the effect of light intensity were explored. MATERIALS AND METHODS E. coli B23 was grown overnight in M9 medium + 0.4% (w/v) glycerol. The culture was diluted to a concentration of 10 5 cells/ml. Anatase plates were sterilized in acetone, dried, and activated under fluorescent light for 5 minutes. Fluorescent light was used as it contains the desired spectrum of light (blue light ~400nm). Samples of different volumes were placed on anatase plates at an equal distance (5.8cm) from the fluorescent light In subsequent experimentation several modifications to the initial protocol were made. Firstly, smaller sample sizes of 150µl, 300µl, 450µl, and 750µl, each in the form of a bubble on the surface of the anatase plates, were tested. The 150 µl sample was placed on the smaller sized plate while the 300µl, 450µl, and 750µl samples were placed on the larger sized plates. These four plates were used for the remainder of the experiment. Cell concentration was also decreased 10-fold to 10 4 cells/ml and all other conditions were held constant. Secondly, the time course 17

Positive effects of fampridine on cognition, fatigue and depression in patients with multiple sclerosis over 2 years

OBJECTIVE: To assess the effects of PR-fampridine on cognitive functioning, fatigue and depression in patients with multiple sclerosis (PwMS). METHODS: Thirty-two PwMS were included in this trial. Cognitive performance was assessed in an open-label and randomized double-blind, placebo-controlled study design using a comprehensive neuropsychological test battery as well as questionnaires examining depression and fatigue. RESULTS: We found significant improvements in cognitive measures assessing alertness (tonic alertness, p = 0.0244 and phasic alertness, p = 0.0428), psychomotor speed (p = 0.0140) as well as verbal fluency (p = 0.0002) during open-label treatment with PR-fampridine. These effects of performance were paralleled by patients' perception of reduced fatigue (physical, p = 0.0131; cognitive, p = 0.0225; total, p = 0.0126). Fampridine-induced improvements in phasic alertness (p = 0.0010) and measures of fatigue (physical, p = 0.0014; cognitive, p = 0.0003; total, p = 0.0005) were confirmed during randomized, double-blind, placebo-controlled assessment in the second year. In addition, we found positive effects of PR-fampridine on depressive symptoms (p = 0.0049). We demonstrated persisting beneficial effects of PR-fampridine on fatigue in PwMS over a period of more than 2 years. Drug responsiveness regarding cognitive performance and fatigue was not limited to walking responders. CONCLUSIONS: Our data demonstrate significant positive effects of treatment with PR-fampridine over 2 years on different cognitive domains as well as fatigue and depression in a cohort of PwMS. These findings imply that PR-fampridine should be considered as symptomatic treatment improving aspects of cognition, fatigue and depression in PwMS

Call for uniform neuropsychological assessment after aneurysmal subarachnoid hemorrhage: Swiss recommendations.

BACKGROUND In a high proportion of patients with favorable outcome after aneurysmal subarachnoid hemorrhage (aSAH), neuropsychological deficits, depression, anxiety, and fatigue are responsible for the inability to return to their regular premorbid life and pursue their professional careers. These problems often remain unrecognized, as no recommendations concerning a standardized comprehensive assessment have yet found entry into clinical routines. METHODS To establish a nationwide standard concerning a comprehensive assessment after aSAH, representatives of all neuropsychological and neurosurgical departments of those eight Swiss centers treating acute aSAH have agreed on a common protocol. In addition, a battery of questionnaires and neuropsychological tests was selected, optimally suited to the deficits found most prevalent in aSAH patients that was available in different languages and standardized. RESULTS We propose a baseline inpatient neuropsychological screening using the Montreal Cognitive Assessment (MoCA) between days 14 and 28 after aSAH. In an outpatient setting at 3 and 12 months after bleeding, we recommend a neuropsychological examination, testing all relevant domains including attention, speed of information processing, executive functions, verbal and visual learning/memory, language, visuo-perceptual abilities, and premorbid intelligence. In addition, a detailed assessment capturing anxiety, depression, fatigue, symptoms of frontal lobe affection, and quality of life should be performed. CONCLUSIONS This standardized neuropsychological assessment will lead to a more comprehensive assessment of the patient, facilitate the detection and subsequent treatment of previously unrecognized but relevant impairments, and help to determine the incidence, characteristics, modifiable risk factors, and the clinical course of these impairments after aSAH