PLoS. Biol.

Certain bacterial adhesins appear to promote a pathogen's extracellular lifestyle rather than its entry into host cells. However, little is known about the stimuli elicited upon such pathogen host-cell interactions. Here, we report that type IV pili (Tfp)-producing Neisseria gonorrhoeae (P(+)GC) induces an immediate recruitment of caveolin-1 (Cav1) in the host cell, which subsequently prevents bacterial internalization by triggering cytoskeletal rearrangements via downstream phosphotyrosine signaling. A broad and unbiased analysis of potential interaction partners for tyrosine-phosphorylated Cav1 revealed a direct interaction with the Rho-family guanine nucleotide exchange factor Vav2. Both Vav2 and its substrate, the small GTPase RhoA, were found to play a direct role in the Cav1-mediated prevention of bacterial uptake. Our findings, which have been extended to enteropathogenic Escherichia coli, highlight how Tfp-producing bacteria avoid host cell uptake. Further, our data establish a mechanistic link between Cav1 phosphorylation and pathogen-induced cytoskeleton reorganization and advance our understanding of caveolin function

The influence of distributed leadership on teachers' organizational commitment: a multilevel approach

In the present study the effects of a cooperative leadership team, distributed leadership, participative decision-making, and context variables on teachers' organizational commitment are investigated. Multilevel analyses on data from 1522 teachers indicated that 9% of the variance in teachers' organizational commitment is attributable to differences between schools. The analyses revealed that especially the presence of a cooperative leadership team and the amount of leadership support played a significantly positive key role in predicting teachers' organizational commitment. Also, participative decision-making and distribution of the supportive leadership function had a significant positive impact on teachers' organizational commitment. In contrast, distribution of the supervisory leadership function and teachers' job experience had a significant negative impact

Ethical leadership in an age of evaluation: implications for whole—school well-being

The evaluation and inspection of many public services, including education, has become increasingly common in most countries in the developed world (McNamara & O’Hara, 2004; MacBeath & McGlynn, 2002). There are various reasons why this may be the case. It can be argued that it is, on the one hand, part of the movement towards low trust policies derived from the ideology of neo-liberalism which seeks to apply the values of the market to the public sector. On the other hand, it can be argued that increased evaluation is a necessary and defensible component of democratic accountability, responsibility and transparency (O’Neill, 2002). The research reported here sets out to explore the idea of a personal vision or core of ethics as being central to educational leadership, through in-depth interviews with a number of school leaders. The chapter begins by briefly placing educational leadership in the modern context, characterised by the paradox of apparently greater decentralisation of responsibility to schools being in fact coupled with a further centralisation of actual power and greatly increased surveillance of performance (Neave, 1998). Relevant developments internationally, and then specifically in the context of Ireland, are described. It is suggested that in Ireland the modern educational context may indeed be creating difficult ethical and moral dilemmas for leaders to face. To see if this is so in practice, five in-depth interviews with school principals are reported. The evidence arising from these interviews indicates that school leaders do feel guided by a strong moral or ethical compass

The relation between school leadership from a distributed perspective and teachers' organizational commitment: examining the source of the leadership function

Purpose: In this study the relationship between school leadership and teachers’ organizational commitment is examined by taking into account a distributed leadership perspective. The relation between teachers’ organizational commitment and contextual variables of teachers’ perceptions of the quality and the source of the supportive and supervisory leadership function, participative decision making, and cooperation within the leadership team are examined. Research Design: A survey was set up involving 1,522 teachers from 46 large secondary schools in Flanders (Belgium). Because the data in the present study have an inherent hierarchical structure, that is, teachers are nested into schools, hierarchical linear modeling techniques are applied. Findings: The analyses reveal that 9% of the variance in teachers’ organizational commitment is attributable to differences between schools. Teachers’ organizational commitment is mainly related to quality of the supportive leadership, cooperation within the leadership team, and participative decision making. Who performed the supportive leadership function plays only a marginally significant positive role. The quality of the supervisory leadership function and the role of the leadership team members in this function were not significantly related to teachers’ organizational commitment. Conclusions: The implications of the findings are that to promote teachers’ organizational commitment teachers should feel supported by their leadership team and that this leadership team should be characterized by group cohesion, role clarity, and goal orientedness. Recommendations for further research are provided

The relationship between the perception of distributed leadership in secondary schools and teachers' and teacher leaders' job satisfaction and organizational commitment

This study investigates the relation between distributed leadership, the cohesion of the leadership team, participative decision-making, context variables, and the organizational commitment and job satisfaction of teachers and teacher leaders. A questionnaire was administered to teachers and teacher leaders (n=1770) from 46 large secondary schools. Multiple regression analyses and path analyses revealed that the study variables explained significant variance in organizational commitment. The degree of explained variance for job satisfaction was considerably lower compared to organizational commitment. Most striking was that the cohesion of the leadership team and the amount of leadership support was strongly related to organizational commitment, and indirectly to job satisfaction. Decentralization of leadership functions was weakly related to organizational commitment and job satisfaction

Counting and effective rigidity in algebra and geometry

The purpose of this article is to produce effective versions of some rigidity results in algebra and geometry. On the geometric side, we focus on the spectrum of primitive geodesic lengths (resp., complex lengths) for arithmetic hyperbolic 2-manifolds (resp., 3-manifolds). By work of Reid, this spectrum determines the commensurability class of the 2-manifold (resp., 3-manifold). We establish effective versions of these rigidity results by ensuring that, for two incommensurable arithmetic manifolds of bounded volume, the length sets (resp., the complex length sets) must disagree for a length that can be explicitly bounded as a function of volume. We also prove an effective version of a similar rigidity result established by the second author with Reid on a surface analog of the length spectrum for hyperbolic 3-manifolds. These effective results have corresponding algebraic analogs involving maximal subfields and quaternion subalgebras of quaternion algebras. To prove these effective rigidity results, we establish results on the asymptotic behavior of certain algebraic and geometric counting functions which are of independent interest.Comment: v.2, 39 pages. To appear in Invent. Mat

Instructional leadership in centralised systems: evidence from Greek high-performing secondary schools

This paper examines the enactment of instructional leadership (IL) in high-performing secondary schools (HPSS), and the relationship between leadership and learning in raising student outcomes and encouraging teachers’ professional learning in the highly centralised context of Greece. It reports part of a comparative research study focused on whether, and to what extent, IL has been embraced by Greek school leaders. The study is exploratory, using a qualitative multiple case design to examine two HPSS in Athens. The research design involved a qualitative approach using several different methods, including semi-structured interviews with school principals, deputy heads, subject teachers and subject advisers, plus observation of leadership practice and meetings and scrutiny of relevant policy documents. The findings show that IL is conceptualised as an informal collaborative leadership practice, interwoven with the official multi-dimension role of Greek principals and their ‘semi-IL’ role. In the absence of official IL ‘actors’, teachers’ leadership has been expanding

Identifying Drug Effects via Pathway Alterations using an Integer Linear Programming Optimization Formulation on Phosphoproteomic Data

Understanding the mechanisms of cell function and drug action is a major endeavor in the pharmaceutical industry. Drug effects are governed by the intrinsic properties of the drug (i.e., selectivity and potency) and the specific signaling transduction network of the host (i.e., normal vs. diseased cells). Here, we describe an unbiased, phosphoproteomicbased approach to identify drug effects by monitoring drug-induced topology alterations. With the proposed method, drug effects are investigated under several conditions on a cell-type specific signaling network. First, starting with a generic pathway made of logical gates, we build a cell-type specific map by constraining it to fit 13 key phopshoprotein signals under 55 experimental cases. Fitting is performed via a formulation as an Integer Linear Program (ILP) and solution by standard ILP solvers; a procedure that drastically outperforms previous fitting schemes. Then, knowing the cell topology, we monitor the same key phopshoprotein signals under the presence of drug and cytokines and we re-optimize the specific map to reveal the drug-induced topology alterations. To prove our case, we make a pathway map for the hepatocytic cell line HepG2 and we evaluate the effects of 4 drugs: 3 selective inhibitors for the Epidermal Growth Factor Receptor (EGFR) and a non selective drug. We confirm effects easily predictable from the drugs’ main target (i.e. EGFR inhibitors blocks the EGFR pathway) but we also uncover unanticipated effects due to either drug promiscuity or the cell’s specific topology. An interesting finding is that the selective EGFR inhibitor Gefitinib is able to inhibit signaling downstream the Interleukin-1alpha (IL-1α) pathway; an effect that cannot be extracted from binding affinity based approaches. Our method represents an unbiased approach to identify drug effects on a small to medium size pathways and is scalable to larger topologies with any type of signaling perturbations (small molecules, 3 RNAi etc). The method is a step towards a better picture of drug effects in pathways, the cornerstone in identifying the mechanisms of drug efficacy and toxicity

Protein Microarray On-Demand: A Novel Protein Microarray System

We describe a novel, simple and low-cost protein microarray strategy wherein the microarrays are generated by printing expression ready plasmid DNAs onto slides that can be converted into protein arrays on-demand. The printed expression plasmids serve dual purposes as they not only direct the synthesis of the protein of interest; they also serve to capture the newly synthesized proteins through a high affinity DNA-protein interaction. To accomplish this we have exploited the high-affinity binding (∼3–7×10 −13 M) of E. coli Tus protein to Ter, a 20 bp DNA sequence involved in the regulation of E. coli DNA replication. In our system, each protein of interest is synthesized as a Tus fusion protein and each expression construct directing the protein synthesis contains embedded Ter DNA sequence. The embedded Ter sequence functions as a capture reagent for the newly synthesized Tus fusion protein. This “all DNA” microarray can be converted to a protein microarray on-demand without need for any additional capture reagent.