Spatial patterning of the Notch ligand Dll4 controls endothelial sprouting in vitro

Angiogenesis, the formation of new blood vessels, is a vital process for tissue growth and development. The Notch cell-cell signalling pathway plays an important role in endothelial cell specification during angiogenesis. Dll4 - Notch1 signalling directs endothelial cells into migrating tip or proliferating stalk cells. We used the directing properties of Dll4 to spatially control endothelial cell fate and the direction of endothelial sprouts. We created linear arrays of immobilized Dll4 using micro contact printing. HUVECs were seeded perpendicular to these Dll4 patterns using removable microfluidic channels. The Notch activating properties of surface immobilized Dll4 were confirmed by qPCR. After induction of sprouting, microscopic images of fluorescently labelled endothelial sprouts were analysed to determine the direction and the efficiency of controlled sprouting (Ecs). Directionality analysis of the sprouts showed the Dll4 pattern changes sprout direction from random to unidirectional. This was confirmed by the increase of Ecs from 54.5 +/- 3.1% for the control, to an average of 84.7 +/- 1.86% on the Dll4 patterned surfaces. Our data demonstrates a surface-based method to spatially pattern Dll4 to gain control over endothelial sprout location and direction. This suggests that spatial ligand patterning can be used to provide control over (neo) vascularization

“I’m only a dog!” : the Rwandan genocide, dehumanisation and the graphic novel

Graphic novels written in response to the 1994 Rwandan genocide do not confine their depictions of traumatic violence to humans, but extend their coverage to show how the genocide impacted on animals and the environment. Through analysis of the presentation of people and their relationships with other species across a range of graphic narratives, this article shows how animal imagery was used to justify inhumane actions during the genocide, and argues that representations of animals remain central to the recuperation processes in a post-genocide context too. Whilst novels and films that respond to the genocide have been the focus of scholarly work (Dauge-Roth, 2010), the graphic novel has yet to receive substantial critical attention. This article therefore unlocks the archive of French-, Dutch- and English-language graphic narratives written in response to the genocide by providing the first in-depth, comparative analysis of their animal representations. It draws on recent methodological approaches derived from philosophy (Derrida, [2008] trans. 2009), postcolonial ecocriticism (Huggan and Tiffin, 2010) and postcolonial trauma theory (Craps, 2012) in order show how human-centred strategies for recovery, and associated symbolic orders that forcefully position the animal outside of human law, continue to engender unequal and potentially violent relationships between humans, and humans and other species. In this way, graphic narratives that gesture towards more equitable relationships between humans, animals and the environment can be seen to support the processes of recovery and reconciliation in post-genocide Rwanda

The use of curved vs. straight instruments in single port access surgery, on standardized box trainer tasks

BACKGROUND: Single-port access (SPA) surgery is a novel surgical technique to create nearly "scarless" surgery. SPA surgery appears to be safe and feasible, but the exposure and handling of tissue may not be optimal. Therefore, the performance of SPA surgery with different instruments used and conventional laparoscopy is compared. METHODS: Fifteen participants (>50 laparoscopic procedures) performed three basic tasks (translocation, clip & cut, and tissue dissection, based on the fundamentals of laparoscopic surgery) in the box trainer in laparoscopy and SPA settings with both (conventional) crossed and curved instruments. All participants completed a questionnaire, which asked their opinion on the use of instruments and preference. RESULTS: Translocation was performed significantly faster in both laparoscopy and SPA crossed than SPA curved (means, 130.3 and 137.7 vs. 170.7 sec; p < 0.001 and p = 0.005). The errors also were less in laparoscopy and SPA crossed (means, 0.9 and 1.2 vs. 1.6), but not significant. The time to complete the dissection was almost equal between laparoscopy and SPA curved settings, but took longer for SPA crossed, although not significantly (148.1 and 150.8 vs. 179.5 sec). The errors only differed significantly between laparoscopy and SPA crossed (means, 0.5 vs. 1.27; p = 0.044). Fourteen participants still favored conventional laparoscopy and one SPA curved. They also thought SPA curved was better than crossed (means, 3.6 vs. 2.47; p = 0.003) and that exposure is superior in curved (means, 3.4 vs. 2.27; p = 0.002). CONCLUSIONS: Although conventional laparoscopy may appear most effective for proper dissection and exposure of tissue, single-port access surgery shows potential. Especially in the tissue dissection task, there is no significant difference in time or errors between conventional laparoscopy and SPA surgery, using specially designed curved instruments. Although the participants favor conventional laparoscopy, this could evolve to a more accepting mind when SPA surgery becomes more available and used in the clinical setting

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Lament as Transitional Justice

Works of human rights literature help to ground the formal rights system in an informal rights ethos. Writers have developed four major modes of human rights literature: protest, testimony, lament, and laughter. Through interpretations of poetry in Carolyn Forché’s anthology, Against Forgetting, and novels from Rwanda, the United States, and Bosnia, I focus on the mode of lament, the literature of mourning. Lament is a social and ritualized form, the purposes of which are congruent with the aims of transitional justice institutions. Both laments and truth commissions employ grieving narratives to help survivors of human rights trauma bequeath to the ghosts of the past the justice of a monument while renewing the survivors’ capacity for rebuilding civil society in the future. Human rights scholars need a broader, extra-juridical meaning for “transitional justice” if we hope to capture its power

Phylogenetics and evolution of Su(var)3-9 SET genes in land plants: rapid diversification in structure and function

<p>Abstract</p> <p>Background</p> <p>Plants contain numerous <it>Su(var)3-9 </it>homologues (<it>SUVH</it>) and related (<it>SUVR</it>) genes, some of which await functional characterization. Although there have been studies on the evolution of plant <it>Su(var)3-9 SET </it>genes, a systematic evolutionary study including major land plant groups has not been reported. Large-scale phylogenetic and evolutionary analyses can help to elucidate the underlying molecular mechanisms and contribute to improve genome annotation.</p> <p>Results</p> <p>Putative orthologs of plant Su(var)3-9 SET protein sequences were retrieved from major representatives of land plants. A novel clustering that included most members analyzed, henceforth referred to as core <it>Su(var)3-9 </it>homologues and related (<it>cSUVHR</it>) gene clade, was identified as well as all orthologous groups previously identified. Our analysis showed that plant Su(var)3-9 SET proteins possessed a variety of domain organizations, and can be classified into five types and ten subtypes. Plant <it>Su(var)3-9 SET </it>genes also exhibit a wide range of gene structures among different paralogs within a family, even in the regions encoding conserved PreSET and SET domains. We also found that the majority of SUVH members were intronless and formed three subclades within the SUVH clade.</p> <p>Conclusions</p> <p>A detailed phylogenetic analysis of the plant <it>Su(var)3-9 SET g</it>enes was performed. A novel deep phylogenetic relationship including most plant <it>Su(var)3-9 SET </it>genes was identified. Additional domains such as SAR, ZnF_C2H2 and WIYLD were early integrated into primordial PreSET/SET/PostSET domain organization. At least three classes of gene structures had been formed before the divergence of <it>Physcomitrella patens </it>(moss) from other land plants. One or multiple retroposition events might have occurred among <it>SUVH </it>genes with the donor genes leading to the V-2 orthologous group. The structural differences among evolutionary groups of plant <it>Su(var)3-9 SET </it>genes with different functions were described, contributing to the design of further experimental studies.</p

Genetics of Host Response to Leishmania tropica in Mice – Different Control of Skin Pathology, Chemokine Reaction, and Invasion into Spleen and Liver

Several hundred million people are exposed to the risk of leishmaniasis, a disease caused by intracellular protozoan parasites of several Leishmania species and transmitted by phlebotomine sand flies. In humans, L. tropica causes cutaneous form of leishmaniasis with painful and long-persisting lesions in the site of the insect bite, but the parasites can also penetrate to internal organs. The relationship between the host genes and development of the disease was demonstrated for numerous infectious diseases. However, the search for susceptibility genes in the human population could be a difficult task. In such cases, animal models may help to discover the role of different genes in interactions between the parasite and the host. Unfortunately, the literature contains only a few publications about the use of animals for L. tropica studies. Here, we report an animal model suitable for genetic, pathological and drug studies in L. tropica infection. We show how the host genotype influences different disease symptoms: skin lesions, parasite dissemination to the lymph nodes, spleen and liver, and increase of levels of chemokines CCL2, CCL3 and CCL5 in serum

Stimuli of Sensory-Motor Nerves Terminate Arterial Contractile Effects of Endothelin-1 by CGRP and Dissociation of ET-1/ETA-Receptor Complexes

Endothelin-1 (ET-1), a long-acting paracrine mediator, is implicated in cardiovascular diseases but clinical trials with ET-receptor antagonists were not successful in some areas. We tested whether the quasi-irreversible receptor-binding of ET-1 (i) limits reversing effects of the antagonists and (ii) can be selectively dissociated by an endogenous counterbalancing mechanism.-receptor complexes.-receptors by ET-1 (i) occur at an antagonist-insensitive site of the receptor and (ii) are selectively terminated by endogenously released CGRP. Hence, natural stimuli of sensory-motor nerves that stimulate release of endogenous CGRP can be considered for therapy of diseases involving ET-1

Associations between job demands, perceptions of noise at work and the psychological contract

Despite the widespread interest in the effects of workload on behaviour, there has been little research on the effects of it on attitudes and values in the workplace and life generally. The aim of the present research was to examine associations between noise exposure (which increases workload) and components of the psychological contract (fairness; trust; organisational commitment; work satisfaction; motivation; organisational citizenship; and intention to stay/quit). 166 workers completed a survey measuring components of the psychological contract, perceptions of noise exposure and other job characteristics. Univariate analyses showed that higher noise exposure was associated with a more negative psychological contract. However, adjustment for other job characteristics, both negative (e.g. job demands) and positive (e.g. control and support), removed the significant effects of noise. These results confirm previous research suggesting that psychosocial stressors have greater behavioural effects than components of the physical working environment such as noise