ArchAlign: coordinate-free chromatin alignment reveals novel architectures

To facilitate identification and characterization of genomic functional elements, we have developed a chromatin architecture alignment algorithm (ArchAlign). ArchAlign identifies shared chromatin structural patterns from high-resolution chromatin structural datasets derived from next-generation sequencing or tiled microarray approaches for user defined regions of interest. We validated ArchAlign using well characterized functional elements, and used it to explore the chromatin structural architecture at CTCF binding sites in the human genome. ArchAlign is freely available at http://www.acsu.buffalo.edu/~mjbuck/ArchAlign.html.     

Cholecystokinin-33 inhibits meal size and prolongs the subsequent intermeal interval

There are various forms of the satiety gut-brain peptide cholecystokinin (CCK), a short, widely utilized form or CCK-8, and a long, putatively more effective form or CCK-33. The issue of which of these forms is a more effective satiety peptide is not resolved. Here, we compared the satiety responses, including the sizes of the first three meals (MS) and intermeal intervals (IMI) as well as their calculated satiety ratios (SR), evoked by both peptides. CCK-8 and 33 (1, 3 and 5 nmol/kg, i.p) reduced the size of the first meal similarly, only CCK-33 prolonged the first IMI and increased SR and both peptides failed to affect second and third MS and IMI. As such, CCK-33 is a more effective satiety peptide than CCK-8. The current results confirm previous findings which showed that both peptides reduce food intake by inhibiting meal size, whereas only CCK-33 reduces food intake by prolonging the intermeal interval.     

Influence of shape-memory stent grafts on local aortic compliance

The effect of repair techniques on the biomechanics of the aorta is poorly understood, resulting in significant levels of postoperative complications for patients worldwide. This study presents a computational analysis of the influence of Nitinol-based devices on the biomechanical performance of a healthy patient-specific human aorta. Simulations reveal that Nitinol stent-grafts stretch the artery wall so that collagen is stretched to a straightened high-stiffness configuration. The high-compliance regime (HCR) associated with low diastolic lumen pressure is eliminated, and the artery operates in a low-compliance regime (LCR) throughout the entire cardiac cycle. The slope of the lumen pressure–area curve for the LCR post-implantation is almost identical to that of the native vessel during systole. This negligible change from the native LCR slope occurs because the stent-graft increases its diameter from the crimped configuration during deployment so that it reaches a low-stiffness unloading plateau. The effective radial stiffness of the implant along this unloading plateau is negligible compared to the stiffness of the artery wall. Provided the Nitinol device unloads sufficiently during deployment to the unloading plateau, the degree of oversizing has a negligible effect on the pressure–area response of the vessel, as each device exerts approximately the same radial force, the slope of which is negligible compared to the LCR slope of the native artery. We show that 10% oversizing based on the observed diastolic diameter in the mid descending thoracic aorta results in a complete loss of contact between the device and the wall during systole, which could lead to an endoleak and stent migration. 20% oversizing reaches the Dacron enforced area limit (DEAL) during the pulse pressure and results in an effective zero-compliance in the later portion of systole.

     

C-reactive protein induces signaling through Fc gamma RIIa on HL-60 granulocytes.

Human C-reactive protein (CRP) at acute phase levels of 10-200 microg/ml triggered the phosphorylation of FcgammaRIIa, Syk kinase, and phospholipase Cgamma2 in granulocytic HL-60 cells. CRP also stimulated translocation to the membrane of both phospholipase Cgamma2 and phosphatidylinositol-3-kinase. The signaling response triggered by CRP was a rapid, early event with kinetics similar to the response elicited by human IgG. Both soluble-aggregated CRP and monomeric CRP cross-linked FcgammaRII to generate a signal of the same intensity. The results are consistent with signaling through the intrinsic immunoreceptor tyrosine-based activation motif of the cytoplasmic domain of FcgammaRIIa, the major CRP-receptor on monocytes and neutrophils that is responsible for CRP-mediated phagocytosis. The signaling events driven by CRP have the potential to regulate infiltrating neutrophil activities.     

Enzymatic activity of the Src homology 2 domain-containing inositol phosphatase is regulated by a plasma membrane location

The negative regulatory role of the Src homology 2 domain-containing inositol 5-phosphatase (SHIP) has been invoked in a variety of receptor-mediated signaling pathways. In B lymphocytes, co-clustering of antigen receptor surface immunoglobulin with FcgammaRIIb promotes the negative effects of SHIP, but how SHIP activity is regulated is unknown. To explore this issue, we investigated the effect of SHIP phosphorylation, receptor tyrosine engagement by its Src homology 2 domain, and membrane recruitment of SHIP on its enzymatic activity. We examined two SHIP phosphorylation kinase candidates, Lyn and Syk, and observed that the Src protein-tyrosine kinase, Lyn is far superior to Syk in its ability to phosphorylate SHIP both in vitro and in vivo. However, we found a minimal effect of phosphorylation or receptor tyrosine engagement of SHIP on its enzymatic activity, whereas membrane localization of SHIP significantly reduced cellular phosphatidylinositol 3,4, 5-triphosphate levels. Based on our results, we propose that a membrane localization of SHIP is the crucial event in the induction of its phosphatase effects.     

The Wavelet-Based Cluster Analysis for Temporal Gene Expression Data

A variety of high-throughput methods have made it possible to generate detailed temporal expression data for a single gene or large numbers of genes. Common methods for analysis of these large data sets can be problematic. One challenge is the comparison of temporal expression data obtained from different growth conditions where the patterns of expression may be shifted in time. We propose the use of wavelet analysis to transform the data obtained under different growth conditions to permit comparison of expression patterns from experiments that have time shifts or delays. We demonstrate this approach using detailed temporal data for a single bacterial gene obtained under 72 different growth conditions. This general strategy can be applied in the analysis of data sets of thousands of genes under different conditions.[1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]     

Howling on the edge: Mantled howler monkey (Alouatta palliata) howling behaviour and anthropogenic edge effects in a fragmented tropical rainforest in Costa Rica

The function of long calling is a subject of interest across animal behaviour study, particularly within primatology. Many primate species have male‐specific long‐distance calls, including platyrrhines like the folivorous howler monkey (Alouatta spp.). Howler monkeys may howl to defend resources such as feeding trees or areas of rich vegetation from other monkey groups. This study tests the ecological resource defence hypothesis for howling behaviour in the mantled howler monkey (Alouatta palliata) and investigates how anthropogenic forest fragmentation may influence howling behaviour. More specifically, this study examines how howling bout rate, duration, precursors and tree species richness, DBH, and canopy cover vary in 100 m anthropogenic edge and interior forest zones at La Suerte Biological Research Station (LSBRS), a fragmented tropical rainforest in Costa Rica. Results show that tree species richness and canopy cover are higher in forest interior at this site, suggesting that monkeys should howl at greater rates in the interior to defend access to these higher‐quality vegetation resources. Overall, our results supported the ecological resource defence hypothesis. The main howl precursor was howling from neighbouring groups. Although howling rate did not differ between forest zones, howling bouts from forest interior were longer, had a greater number of howls per bout and were preceded by different precursors than howls from anthropogenic edge zones, including more howls from neighbouring groups. Our findings provide some of the first evidence for behavioural edge effects in primate vocal communication behaviour.