Revisiting the mechanism of coagulation factor XIII activation and regulation from a structure/functional perspective

The activation and regulation of coagulation Factor XIII (FXIII) protein has been the subject of active research for the past three decades. Although discrete evidence exists on various aspects of FXIII activation and regulation a combinatorial structure/functional view in this regard is lacking. In this study, we present results of a structure/function study of the functional chain of events for FXIII. Our study shows how subtle chronological submolecular changes within calcium binding sites can bring about the detailed transformation of the zymogenic FXIII to its activated form especially in the context of FXIIIA and FXIIIB subunit interactions. We demonstrate what aspects of FXIII are important for the stabilization (first calcium binding site) of its zymogenic form and the possible modes of deactivation (thrombin mediated secondary cleavage) of the activated form. Our study for the first time provides a structural outlook of the FXIIIA 2 B 2 heterotetramer assembly, its association and dissociation. The FXIIIB subunits regulatory role in the overall process has also been elaborated upon. In summary, this study provides detailed structural insight into the mechanisms of FXIII activation and regulation that can be used as a template for the development of future highly specific therapeutic inhibitors targeting FXIII in pathological conditions like thrombosis

the italian didactic tradition

Starting with a historic overview highlighting the increasing interest and involvement of the community of mathematicians in educational issues, the chapter outlines some of the crucial features that shaped Italian didactics and, more specifically, the emergence of research studies on mathematics education. Some of these features are related to local conditions, for instance, the high degree of freedom left to the teacher in the design and realization of didactic interventions. The specificity of the Italian case can also be highlighted through a comparison with the reality of other countries. The fruitfulness of this comparison is presented by reporting on collective and personal collaboration experiences between the French and Italian research communities. A final contribution, coming from East Asia, puts the Italian tradition under the lens of a completely new eye, and invites reflection upon historical and institutional aspects of the Italian tradition

Seeking research-grounded solutions to problems of practice: classroom-based interventions in mathematics education

Research on classroom-based interventions in mathematics education has two core aims: (a) to improve classroom practice by engineering ways to act upon problems of practice; and (b) to deepen theoretical understanding of classroom phenomena that relate to these problems. Although there are notable examples of classroom-based intervention studies in mathematics education research since at least the 1930s, the number of such studies is small and acutely disproportionate to the number of studies that have documented problems of classroom practice for which solutions are sorely needed. In this paper we first make a case for the importance of research on classroom-based interventions and identify three important features of this research, which we then use to review the papers in this special issue. We also consider the issue of 'scaling up' promising classroom-based interventions in mathematics education, and we discuss a major obstacle that most such interventions find on the way to scaling up. This obstacle relates to their long duration, which means that possible adoption of these interventions would require practitioners to do major reorganizations of the mathematics curricula they follow in order to accommodate the time demands of the interventions. We argue that it is important, and conjecture that it is possible, to design interventions of short duration in mathematics education to alleviate major problems of classroom practice. Such interventions would be more amenable to scaling up, for they would allow more control over confounding variables and would make more practicable their incorporation into existing curriculum structures. © 2013 FIZ Karlsruhe

Laparoscopic treatment of abdominal unicentric castleman’s disease: a case report and literature review

Castleman's disease is a rare lymphoproliferative disorder of unknown etiology that most commonly presents as a mediastinal nodal mass. It is exceptionally uncommon for Castleman's disease to present in the mesentery and, only 53 cases have ever been described in the literature. Standard treatment for this lymphoproliferative disorder involving a single node is a complete "en bloc" surgical resection which has proven to be a curative approach in almost all cases without recurrence after 20 years of follow up. All 53 reported cases of mesenteric Castleman's disease, except one, were treated with laparotomy