Network of protein interactions within the Drosophila inner kinetochore.

The kinetochore provides a physical connection between microtubules and the centromeric regions of chromosomes that is critical for their equitable segregation. The trimeric Mis12 sub-complex of the Drosophila kinetochore binds to the mitotic centromere using CENP-C as a platform. However, knowledge of the precise connections between Mis12 complex components and CENP-C has remained elusive despite the fundamental importance of this part of the cell division machinery. Here, we employ hydrogen-deuterium exchange coupled with mass spectrometry to reveal that Mis12 and Nnf1 form a dimer maintained by interacting coiled-coil (CC) domains within the carboxy-terminal parts of both proteins. Adjacent to these interacting CCs is a carboxy-terminal domain that also interacts with Nsl1. The amino-terminal parts of Mis12 and Nnf1 form a CENP-C-binding surface, which docks the complex and thus the entire kinetochore to mitotic centromeres. Mutational analysis confirms these precise interactions are critical for both structure and function of the complex. Thus, we conclude the organization of the Mis12-Nnf1 dimer confers upon the Mis12 complex a bipolar, elongated structure that is critical for kinetochore function.The work was funded by the Foundation for Polish Science via an International PhD Projects Programme grant to MR and MD; Polish National Science Center via collaborative Harmonia 5 grant to MD and DMG (2013/10/M/NZ2/00298), and by the Medical Research Council and Cancer Research UK via programme grants to DMG. ZL was on leave from the Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary, and supported by the FEBS Long Term fellowship. We are grateful to Magdalena Kaus-Drobek and Kinga Fituch for help with the structural characterisation of peptides. We thank Andrea Musacchio and his group for sharing their data before publication.This is the final version of the article. It first appeared from Royal Society Publishing via http://dx.doi.org/10.1098/rsob.15023

Polskie zalecenia postępowania w rzadkich niedoborach osoczowych czynników krzepnięcia

The Working Group for Haemostasis of the Polish Society of Haematology and Transfusion Medicine presents the principles of diagnosis and treatment of rare hereditary clotting factor deficiencies. They are based on the World Federation of Haemophilia guidelines as well as on the results of studies published in the international journals, and authors’ personal experience. Hematologia 2011; 2, 4: 303–310Grupa ds. Hemostazy Polskiego Towarzystwa Hematologów i Transfuzjologów przedstawia zasady rozpoznawania i leczenia rzadko występujących wrodzonych niedoborów osoczowych czynników krzepnięcia. Zalecenia te opierają się na wytycznych opublikowanych przez Światową Organizację Hemofilii, na wynikach badań opublikowanych w międzynarodowym piśmiennictwie i na własnym doświadczeniu autorów. Hematologia 2011; 2, 4: 303–31

Część II: Wytyczne postępowania w hemofilii A i B powikłanej inhibitorem czynnika VIII i IX (2 wydanie)

In this article, the Working Group for Haemostasis of the Polish Society of Haematology and Blood Transfusion updates the principles of diagnosis and treatment of haemophilia A and B complicated by factor VIII or IX inhibitors, which were published for the first time in 2008. In the first part of the Guidelines published in 2016, the management of haemophilia A and B without factor VIII and IX inhibitors was dealt with

Management of inherited thrombocytopenia. Recommendations of the Group on Hemostasis of the Polish Society of Hematology and Transfusion Medicine, 2019

Inherited thrombocytopenias (IT) comprise a highly heterogeneous group of rare haemostatic disorders which vary in terms of degree of thrombocytopenia, platelet size, pattern of inheritance and clinical course. Due to difficult diagnosis and frequently mild clinical phenotype these disorders are often underdiagnosed. The purpose of this review is to provide clinical and laboratory characteristics of the most important types of IT. The currently available therapeutic options for these conditions are also recapitulated and discussed

Część I: Wytyczne postępowania w hemofilii A i B niepowikłanej inhibitorem czynnika VIII i IX (wydanie zaktualizowane)

In this document, Working Group for Haemostasis of the Polish Society of Haematology and Blood Transfusion updates the principles of diagnosis and treatment of haemophilia A and B, published for the first time in 2008. In a companion paper (part II), the management of haemophilia A and B complicated by factor VIII and IX inhibitors will be covered