‘To fill yourself with goodness’: revolutionary self-making in Bolivarian Venezuela

This article explores how utopian visions are articulated by chavista activists in Venezuela through the practice of 'revolutionary self-making'. Drawing on ethnographic fieldwork conducted in the city of Valencia between 2008 and 2012, it aims to demonstrate how close attention to the formation of new moral and spiritual selves is an integral part of the way that chavistas enact and experience political protagonism. In doing so, the article seeks to provide a ground level view of utopian visions as they are manifested discursively and practically in everyday life

Manipulating the 3D organization of the largest synthetic yeast chromosome

Whether synthetic genomes can power life has attracted broad interest in the synthetic biology field. Here, we report de novo synthesis of the largest eukaryotic chromosome thus far, synIV, a 1,454,621-bp yeast chromosome resulting from extensive genome streamlining and modification. We developed megachunk assembly combined with a hierarchical integration strategy, which significantly increased the accuracy and flexibility of synthetic chromosome construction. Besides the drastic sequence changes, we further manipulated the 3D structure of synIV to explore spatial gene regulation. Surprisingly, we found few gene expression changes, suggesting that positioning inside the yeast nucleoplasm plays a minor role in gene regulation. Lastly, we tethered synIV to the inner nuclear membrane via its hundreds of loxPsym sites and observed transcriptional repression of the entire chromosome, demonstrating chromosome-wide transcription manipulation without changing the DNA sequences. Our manipulation of the spatial structure of synIV sheds light on higher-order architectural design of the synthetic genomes. </p

Restoring brain function after stroke - bridging the gap between animals and humans

Stroke is the leading cause of complex adult disability in the world. Recovery from stroke is often incomplete, which leaves many people dependent on others for their care. The improvement of long-term outcomes should, therefore, be a clinical and research priority. As a result of advances in our understanding of the biological mechanisms involved in recovery and repair after stroke, therapeutic opportunities to promote recovery through manipulation of poststroke plasticity have never been greater. This work has almost exclusively been carried out in preclinical animal models of stroke with little translation into human studies. The challenge ahead is to develop a mechanistic understanding of recovery from stroke in humans. Advances in neuroimaging techniques now enable us to reconcile behavioural accounts of recovery with molecular and cellular changes. Consequently, clinical trials can be designed in a stratified manner that takes into account when an intervention should be delivered and who is most likely to benefit. This approach is expected to lead to a substantial change in how restorative therapeutic strategies are delivered in patients after stroke

Reliability and validity of daily self-monitoring by smartphone application for health-related quality-of-life, antiretroviral adherence, substance use, and sexual behaviors among people living with HIV.

This paper examines inter-method reliability and validity of daily self-reports by smartphone application compared to 14-day recall web-surveys repeated over 6&nbsp;weeks with people living with HIV (PLH). A participatory sensing framework guided participant-centered design prioritizing external validity of methods for potential applications in both research and self-management interventions. Inter-method reliability correlations were consistent with prior research for physical and mental health quality-of-life (r&nbsp;=&nbsp;0.26-0.61), antiretroviral adherence (r&nbsp;=&nbsp;0.70-0.73), and substance use (r&nbsp;=&nbsp;0.65-0.92) but not for detailed sexual encounter surveys (r&nbsp;=&nbsp;0.15-0.61). Concordant and discordant pairwise comparisons show potential trends in reporting biases, for example, lower recall reports of unprotected sex or alcohol use, and rounding up errors for frequent events. Event-based reporting likely compensated for modest response rates to daily time-based prompts, particularly for sexual and drug use behaviors that may not occur daily. Recommendations are discussed for future continuous assessment designs and analyses

Reliability and validity of daily self-monitoring by smartphone application for health-related quality-of-life, antiretroviral adherence, substance use, and sexual behaviors among people living with HIV.

This paper examines inter-method reliability and validity of daily self-reports by smartphone application compared to 14-day recall web-surveys repeated over 6&nbsp;weeks with people living with HIV (PLH). A participatory sensing framework guided participant-centered design prioritizing external validity of methods for potential applications in both research and self-management interventions. Inter-method reliability correlations were consistent with prior research for physical and mental health quality-of-life (r&nbsp;=&nbsp;0.26-0.61), antiretroviral adherence (r&nbsp;=&nbsp;0.70-0.73), and substance use (r&nbsp;=&nbsp;0.65-0.92) but not for detailed sexual encounter surveys (r&nbsp;=&nbsp;0.15-0.61). Concordant and discordant pairwise comparisons show potential trends in reporting biases, for example, lower recall reports of unprotected sex or alcohol use, and rounding up errors for frequent events. Event-based reporting likely compensated for modest response rates to daily time-based prompts, particularly for sexual and drug use behaviors that may not occur daily. Recommendations are discussed for future continuous assessment designs and analyses

Pharmacological Inhibition of Lysine-Specific Demethylase 1A Reduces Atherosclerotic Lesion Formation in Apolipoprotein E-Deficient Mice by a Mechanism Involving Decreased Oxidative Stress and Inflammation; Potential Implications in Human Atherosclerosis

Dysregulated epigenetic mechanisms promote transcriptomic and phenotypic alterations in cardiovascular diseases. The role of histone methylation-related pathways in atherosclerosis is largely unknown. We hypothesize that lysine-specific demethylase 1A (LSD1/KDM1A) regulates key molecular effectors and pathways linked to atherosclerotic plaque formation. Human non-atherosclerotic and atherosclerotic tissue specimens, ApoE-/- mice, and in vitro polarized macrophages (Mac) were examined. Male ApoE-/- mice fed a normal/atherogenic diet were randomized to receive GSK2879552, a highly specific LSD1 inhibitor, or its vehicle, for 4 weeks. The mRNA and protein expression levels of LSD1/KDM1A were significantly elevated in atherosclerotic human carotid arteries, atherosclerotic aortas of ApoE-/- mice, and M1-Mac. Treatment of ApoE-/- mice with GSK2879552 significantly reduced the extent of atherosclerotic lesions and the aortic expression of NADPH oxidase subunits (Nox1/2/4, p22phox) and 4-hydroxynonenal-protein adducts. Concomitantly, the markers of immune cell infiltration and vascular inflammation were significantly decreased. LSD1 blockade down-regulated the expression of genes associated with Mac pro-inflammatory phenotype. Nox subunit transcript levels were significantly elevated in HEK293 reporter cells overexpressing LSD1. In experimental atherosclerosis, LSD1 mediates the up-regulation of molecular effectors connected to oxidative stress and inflammation. Together, these data indicate that LSD1-pharmacological interventions are novel targets for supportive therapeutic strategies in atherosclerosis

Masking of the PTS1 of Lys12 does not affect growth under lysine-limiting conditions.

Serial dilutions of logarithmically growing cells of indicated strains were spotted on media with or without lysine and incubated at 30°C. (TIF)</p

Candidates for proteins dually targeted to mitochondria and peroxisomes.

Candidates for proteins dually targeted to mitochondria and peroxisomes.</p

Suppression of Δ<i>mdm12</i> does not prevent formation of aberrant peroxisomes.

(A) Serial dilutions of logarithmically growing cells of indicated strains were spotted on indicated media and incubated at 30°C. (B) Fluorescence microscopic images of Δmdm10 cells (SUP-) or Δmdm10 cells with a suppressor mutation (SUP+) co-expressing the peroxisomal marker Ant1-YFP (magenta) and the mitochondrial inner membrane protein Tim50-CFP (green). Scale bar represents 5 μm. (C) The number of peroxisomes per cell was quantified in the indicated strains. Quantifications are based on n = 3 experiments. Each color represents 1 experiment. Error bars represent standard error of the mean. P-values were calculated with a one-way ANOVA combined with a Tukey test. Underlying data for quantifications can be found in S1 Data. (TIF)</p