Exploiting gene deletion fitness effects in yeast to understand the modular architecture of protein complexes under different growth conditions

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background Understanding how individual genes contribute towards the fitness of an organism is a fundamental problem in biology. Although recent genome-wide screens have generated abundant data on quantitative fitness for single gene knockouts, very few studies have systematically integrated other types of biological information to understand how and why deletion of specific genes give rise to a particular fitness effect. In this study, we combine quantitative fitness data for single gene knock-outs in yeast with large-scale interaction discovery experiments to understand the effect of gene deletion on the modular architecture of protein complexes, under different growth conditions. Results Our analysis reveals that genes in complexes show more severe fitness effects upon deletion than other genes but, in contrast to what has been observed in binary protein-protein interaction networks, we find that this is not related to the number of complexes in which they are present. We also find that, in general, the core and attachment components of protein complexes are equally important for the complex machinery to function. However, when quantifying the importance of core and attachments in single complex variations, or isoforms, we observe that this global trend originates from either the core or the attachment components being more important for strain fitness, both being equally important or both being dispensable. Finally, our study reveals that different isoforms of a complex can exhibit distinct fitness patterns across growth conditions. Conclusion This study presents a powerful approach to unveil the molecular basis for various complex phenotypic profiles observed in gene deletion experiments. It also highlights some interesting cases of potential functional compensation between protein paralogues and suggests a new piece to fit into the histone-code puzzle.Published versio

sCR1sLeX reduces lung allograft ischemia-reperfusion injury but does not ameliorate acute rejection

Background: Combined inhibition of complement and leukocyte adhesion by sCR1sLeX reduces lung allograft dysfunction up to 24 h. In the present study its effect on graft function and acute rejection was evaluated up to 5 days after experimental transplantation. Methods: Orthotopic single left lung transplantation was performed in 35 male rats (Brown Norway to Fischer 344) after a total ischemic time of 20 h. Two groups were assessed after 1, 3, and 5 days post-transplant, respectively (n=5 per group and time point): controls vs. recipients which received 10 mg/kg sCR1sLeX 15 min prior to reperfusion. In addition, five animals received 10 mg/kg per day sCR1sLeX for 5 days. For blood gas analysis of the graft, the contralateral lung was occluded for 5 min to assess graft function. Lung grafts were flushed, and histological grading was performed in blinded fashion according to the International Society for Heart and Lung Transplantation criteria. Results: Graft PaO2 in recipients treated with sCR1sLeX was superior on day 1 (383±118 vs. 56±15 mmHg; P≪0.0001) and day 3 (446±48 vs. 231±108 mmHg; P≪0.0001). Five days after transplantation, no difference in PaO2 was found (61±28 vs. 83±31 mmHg; P=0.59). Repeated treatment with sCR1sLeX for 5 days did not improve PaO2 (64±5 mmHg; P=0.65 vs. control; P=0.93 vs. sCR1sLeX). At any time point, there was no difference in the degree of rejection between groups. Conclusions: In this model sCR1sLeX provided marked improvement of graft function up to 3 days, but inhibition of both complement system and selectin dependent leukocyte adhesion failed to protect against acute rejectio

A dimensionally continued Poisson summation formula

We generalize the standard Poisson summation formula for lattices so that it operates on the level of theta series, allowing us to introduce noninteger dimension parameters (using the dimensionally continued Fourier transform). When combined with one of the proofs of the Jacobi imaginary transformation of theta functions that does not use the Poisson summation formula, our proof of this generalized Poisson summation formula also provides a new proof of the standard Poisson summation formula for dimensions greater than 2 (with appropriate hypotheses on the function being summed). In general, our methods work to establish the (Voronoi) summation formulae associated with functions satisfying (modular) transformations of the Jacobi imaginary type by means of a density argument (as opposed to the usual Mellin transform approach). In particular, we construct a family of generalized theta series from Jacobi theta functions from which these summation formulae can be obtained. This family contains several families of modular forms, but is significantly more general than any of them. Our result also relaxes several of the hypotheses in the standard statements of these summation formulae. The density result we prove for Gaussians in the Schwartz space may be of independent interest.Comment: 12 pages, version accepted by JFAA, with various additions and improvement

On the Second Law of thermodynamics and the piston problem

The piston problem is investigated in the case where the length of the cylinder is infinite (on both sides) and the ratio $m/M$ is a very small parameter, where $m$ is the mass of one particle of the gaz and $M$ is the mass of the piston. Introducing initial conditions such that the stochastic motion of the piston remains in the average at the origin (no drift), it is shown that the time evolution of the fluids, analytically derived from Liouville equation, agrees with the Second Law of thermodynamics. We thus have a non equilibrium microscopical model whose evolution can be explicitly shown to obey the two laws of thermodynamics.Comment: 29 pages, 9 figures submitted to Journal of Statistical Physics (2003

Reconstructing institutional complexity in practice: A relational model of institutional work and complexity

This article develops a relational model of institutional work and complexity. This model advances current institutional debates on institutional complexity and institutional work in three ways. First, it provides a relational and dynamic perspective on institutional complexity by explaining how constellations of logics - and their degree of internal contradiction - are constructed rather than given. Second, it refines our current understanding of agency, intentionality and effort in institutional work by demonstrating how different dimensions of agency interact dynamically in the institutional work of reconstructing institutional complexity. Third, it situates institutional work in the everyday practice of individuals coping with the institutional complexities of their work. In doing so, it reconnects the construction of institutionally complex settings to the actions and interactions of the individuals who inhabit them

Sailing into a dilemma : an economic and legal analysis of an EU trading scheme for maritime emissions

On the basis of a joint economic and legal analysis, we evaluate the effects of a “regional” (European) emission trading scheme aiming at reducing emissions of international shipping. The focus lies on the question which share of emissions from maritime transport activities to and from the EU can and should be included in such a system. Our findings suggest that the attempt to implement an EU maritime ETS runs into a dilemma. It is not possible to design a system that achieves emission reductions in a cost efficient manner and is compatible with international law

How hybrids manage growth and social–business tensions in global supply chains: the case of impact sourcing

This study contributes to the growing interest in how hybrid organizations manage paradoxical social–business tensions. Our empirical case is ‘‘impact sourcing’’— hybrids in global supply chains that hire staff from disadvantaged communities to provide services to business clients. We identify two major growth orientations— ‘‘community-focused’’ and ‘‘client-focused’’ growth—their inherent tensions and ways that hybrids manage them. The former favors slow growth and manages tensions through highly integrated client and community relations; the latter promotes faster growth and manages client and community relations separately. Both growth orientations address social–business tensions in particular ways, but also create latent constraints that manifest when entrepreneurial aspirations conflict with the current growth path. In presenting and discussing our findings, we introduce preempting management practices of tensions, and the importance of geographic embeddedness and distance to the paradox literature

Anatomical and procedural features associated with aortic root rupture during balloon-expandable transcatheter aortic valve replacement

Aortic root rupture is a major concern with balloon-expandable transcatheter aortic valve replacement (TAVR). We sought to identify predictors of aortic root rupture during balloon-expandable TAVR by using multidetector computed tomography

Maintenance of cross-sector partnerships: the role of frames in sustained collaboration

We examine the framing mechanisms used to maintain a cross-sector partnership (XSP) that was created to address a complex long-term social issue. We study the first eight years of existence of an XSP that aims to create a market for recycled phosphorus, a nutrient that is critical to crop growth but whose natural reserves have dwindled significantly. Drawing on 27 interviews and over 3,000 internal documents, we study the evolution of different frames used by diverse actors in an XSP. We demonstrate the role of framing in helping actors to avoid some of the common pitfalls for an XSP, such as debilitating conflict, and in creating sufficient common ground to sustain collaboration. As opposed to a commonly held assumption in the XSP literature, we find that collaboration in a partnership does not have to result in a unanimous agreement around a single or convergent frame regarding a contentious issue. Rather, successful collaboration between diverse partners can also be achieved by maintaining a productive tension between different frames through ‘optimal’ frame plurality – not excessive frame variety that may prevent agreements from emerging, but the retention of a select few frames and the deletion of others towards achieving a narrowing frame bandwidth. One managerial implication is that resources need not be focussed on reaching a unanimous agreement among all partners on a single mega-frame vis-à-vis a contentious issue, but can instead be used to kindle a sense of unity in diversity that allows sufficient common ground to emerge, despite the variety of actors and their positions

Cognitive frames in corporate sustainability: managerial sensemaking with paradoxical and business case frames

Corporate sustainability confronts managers with tensions between complex economic, environmental, and social issues. Drawing on the literature on managerial cognition, corporate sustainability, and strategic paradoxes, we develop a cognitive framing perspective on corporate sustainability. We propose two cognitive frames—a business case frame and a paradoxical frame—and explore how differences between them in cognitive content and structure influence the three stages of the sensemaking process—that is, managerial scanning, interpreting, and responding with regard to sustainability issues. We explain how the two frames lead to differences in the breadth and depth of scanning, differences in issue interpretations in terms of sense of control and issue valence, and different types of responses that managers consider with regard to sustainability issues. By considering alternative cognitive frames, our argument contributes to a better understanding of managerial decision making regarding ambiguous sustainability issues, and it develops the underlying cognitive determinants of the stance that managers adopt on sustainability issues. This argument offers a cognitive explanation for why managers rarely push for radical change when faced with complex and ambiguous issues, such as sustainability, that are characterized by conflicting yet interrelated aspects