HDAC inhibition results in widespread alteration of the histone acetylation landscape and BRD4 targeting to gene bodies

1. Download : Download high-res image (115KB)
2. Download : Download full-size image

     

The effect of diazepam on potassium contractures, contraction threshold, and resting tension in rat skeletal muscles

The effects of diazepam on potassium contractures, contraction threshold, and resting tension have been examined in rat soleus muscle fibres. Two actions of the drug were defined that could not be attributed to changes in the resting membrane potential or depolarization in high potassium solutions. The major effect was an increase in the amplitude of submaximal tension during either twitches or potassium contractures and an increase in resting tension. At 400 microM diazepam, there was (a) a fourfold increase in 40 mM potassium contracture tension, (b) a negative shift of 8 mV in the membrane potential for half maximum tension estimated from the best fit of a Boltzmann-type equation to average potassium contracture data, (c) a negative shift of 8 mV in the threshold for contraction measured under voltage clamp conditions, and (d) a contracture of variable amplitude to a level that was occasionally equivalent to maximum tetanic tension. These potentiating actions of diazepam depended on drug concentration within the range of 100-800 microM. In contrast, the second effect of diazepam, depression of maximum tension by 10-15%, was independent of drug concentration between 100 and 400 microM. The results support the idea that diazepam produces an increase in resting myoplasmic calcium concentrations.     

Effects of insulin on cardiac lysosomes and protein degradation

Hearts perfused in the absence of added insulin had 1) accelerated rates of protein degradation, as assessed by release of phenylalanine and tyrosine; 2) increased rates of release of seven other amino acids; 3) decreased lysosomal latency and sedimentable lysosomal enzyme activity; 4) increased numbers of autophagic vacuoles in cardiac muscle cells; and 5) decreased activity of beta-N-acetylglucosaminidase in dense lysosomes (1.06-1.09 g/ml), as compared to hearts perfused in the presence of the hormone. After 3 h of perfusion in the absence of insulin, the changes that developed in protein degradation, lysosomal latency, and sedimentability, and in enzyme activity in dense lysosomes, were reversed by insulin addition during 90 min of subsequent perfusion. These studies suggest a role for insulin in controlling the activity of the lysosomal system and the involvement of this system in protein degradation, particularly in insulin-deprived tissue.     

Morphological traits mediate fish occurrences in oil palm-impacted tropical streams

1. Land-use change is a leading driver of biodiversity loss, especially in tropical fresh waters where the conversion of natural forest to monoculture plantations impacts freshwater fish assemblages. The environmental pathways underpinning shifts in fish assemblages, however, are poorly understood, but could potentially be inferred from trait–environment relationships.
2. We addressed this knowledge gap using eco-morphological traits to explain fish occurrences in oil palm-impacted streams of the Endau drainage in Peninsular Malaysia. We also investigated how traits relate to differences in environmental conditions associated with land-use change. We then integrate findings from the above to test how potential pathways of land-use driven environmental changes can impact species occurrences through effects on life history, feeding habits, and mobility.
3. Mixed-effects models show that fishes with superior (upward-facing) mouths and low body mass were more likely to occur in oil palm streams than forest streams, and these traits were associated with grass-dominated riparian zones and reduced woody debris in oil palm streams, respectively. Structural equation models show that mouth positions statistically mediated the effect of riparian vegetation on fish species occurrences in oil palm streams. Specifically, fishes with superior mouths were more likely to feed on terrestrial invertebrates.
4. Our analysis of easily measurable traits revealed pathways of land-use impact that are potentially more widely applicable than conventional taxa-based approaches. Fishes with superior mouths tended to occur in oil palm streams as they were able to more effectively exploit inputs of terrestrial invertebrates that are potentially associated with grass-dominated riparian vegetation.
5. Moreover, shifts in traits may suggest land-use driven changes in stream ecosystem functioning (e.g. in terms of the role of terrestrial subsidies), thereby informing targeted management actions in land-use impacted habitats (e.g. retention/restoration of riparian trees).

     

Simple Branched Arginine-Based Structures can Enhance the Cellular Uptake of Peptide Cargos

In an attempt to design delivery vehicles to enable epitope-based vaccine uptake, we investigated the properties of a variety of synthetic, branched cationic structures. We found that branched compounds based on arginine or lysine were able to facilitate internalization of peptide cargo into cells to different degrees. Branched constructs containing only two arginine residues (R₂) were not only able to bind to cells more efficiently than constructs with two lysine residues (K₂) but were also internalized within vesicle like compartments in the cell. The extent of binding and uptake was enhanced when additional arginine residues were incorporated to form a tetra arginine construct (R₄). An investigation into the kinetics and dose dependence of cellular uptake of these arginine-based constructs demonstrated that binding and internalization is a rapid and efficient event. We also found uptake of the peptide epitope TYQRTRALV was enhanced when it was coupled to R₄. This approach may prove useful for introducing peptide epitopes into antigen presenting cells as self-adjuvanting structures and also for delivery of other peptides into different specialized cells.     

A constant pool of Lgr5+ intestinal stem cells is required for intestinal homeostasis

1. Download : Download high-res image (122KB)
2. Download : Download full-size image