The dynamic protein Knl1 - a kinetochore rendezvous

Knl1 (also known as CASC5, UniProt Q8NG31) is an evolutionarily conserved scaffolding protein that is required for proper kinetochore assembly, spindle assembly checkpoint (SAC) function and chromosome congression. A number of recent reports have confirmed the prominence of Knl1 in these processes and provided molecular details and structural features that dictate Knl1 functions in higher organisms. Knl1 recruits SAC components to the kinetochore and is the substrate of certain protein kinases and phosphatases, the interplay of which ensures the exquisite regulation of the aforementioned processes. In this Commentary, we discuss the overall domain organization of Knl1 and the roles of this protein as a versatile docking platform. We present emerging roles of the protein interaction motifs present in Knl1, including the RVSF, SILK, MELT and KI motifs, and their role in the recruitment and regulation of the SAC proteins Bub1, BubR1, Bub3 and Aurora B. Finally, we explore how the regions of low structural complexity that characterize Knl1 are implicated in the cooperative interactions that mediate binding partner recognition and scaffolding activity by Knl1

Comparative evaluation of prescriptions of MBBS and BAMS doctors using WHO prescribing indicators

Background: Irrational prescribing is a global problem. The present study was undertaken to identify the problem of irrational medicine use by Bachelor of Medicine and Bachelor of Surgery (MBBS) and Bachelor of Ayurvedic Medicine and Surgery (BAMS) doctors in outpatient setting, by using WHO prescribing indicators. Materials and Methods: This study was carried out in Vishrantwadi, Pune, India. 250 prescriptions were collected from MBBS doctors and 250 prescriptions were collected from BAMS doctors and their prescription pattern was analyzed using WHO prescribing indicators. Results: Average number of medicines per prescription was 2.4 for MBBS and 3.04 for BAMS doctors. Percentage of prescriptions with antibiotics and with injections was significantly more in BAMS doctors. Antibiotics, gastrointestinal system related medicines, vitamins and iron preparations were prescribed more by BAMS doctors. Percentage of irrational fixed dose combinations prescribed by BAMS doctors was more (57.2%) as compared to MBBS doctors (28.6%). Conclusions: In the present study, although the prescribing patterns of both MBBS as well as BAMS doctors are not satisfactory; the BAMS doctors seem to prescribe more irrationally as compared to MBBS doctors

Experimental and computational framework for a dynamic protein atlas of human cell division.

Essential biological functions, such as mitosis, require tight coordination of hundreds of proteins in space and time. Localization, the timing of interactions and changes in cellular structure are all crucial to ensure the correct assembly, function and regulation of protein complexes(1-4). Imaging of live cells can reveal protein distributions and dynamics but experimental and theoretical challenges have prevented the collection of quantitative data, which are necessary for the formulation of a model of mitosis that comprehensively integrates information and enables the analysis of the dynamic interactions between the molecular parts of the mitotic machinery within changing cellular boundaries. Here we generate a canonical model of the morphological changes during the mitotic progression of human cells on the basis of four-dimensional image data. We use this model to integrate dynamic three-dimensional concentration data of many fluorescently knocked-in mitotic proteins, imaged by fluorescence correlation spectroscopy-calibrated microscopy(5). The approach taken here to generate a dynamic protein atlas of human cell division is generic; it can be applied to systematically map and mine dynamic protein localization networks that drive cell division in different cell types, and can be conceptually transferred to other cellular functions