RIBFIND: a web server for identifying rigid bodies in protein structures and to aid flexible fitting into cryo EM maps

Motivation: To better analyze low-resolution cryo electron microscopy maps of macromolecular assemblies, component atomic structures frequently have to be flexibly fitted into them. Reaching an optimal fit and preventing the fitting process from getting trapped in local minima can be significantly improved by identifying appropriate rigid bodies in the fitted component. Results: Here we present the RIBFIND server, a tool for identifying rigid bodies in protein structures. The server identifies rigid bodies in proteins by calculating spatial proximity between their secondary structural elements. Availability: The RIBFIND web server and its standalone program are available at http://ribfind.ismb.lon.ac.uk

Enhancing the professionalisation of student affairs through assessment

The past decades have seen an increase in the attention and focus of student affairs workin Africa. As the profession works to strengthen its reputation and value within highereducation through conferences, organisations and publications, student affairs professionalscan also raise the stature of the profession through work on their individual campuses.Engaging in assessment may be one such opportunity. As a way to create a commonlanguage regarding student affairs assessment, this paper provides an overview of thedefinitions, types and purposes of assessment. The thought is that viewing assessment as anintegral, rather than ‘extra’ aspect of student affairs and incorporating these activities withintheir work, student affairs professionals will not only improve the effectiveness of theirwork with students but also can help legitimise the field as a profession

Enhancing the professionalisation of student affairs through assessment

The past decades have seen an increase in the attention and focus of student affairs work in Africa. As the profession works to strengthen its reputation and value within higher education through conferences, organisations and publications, student affairs professionals can also raise the stature of the profession through work on their individual campuses. Engaging in assessment may be one such opportunity. As a way to create a common language regarding student affairs assessment, this paper provides an overview of the definitions, types and purposes of assessment. The thought is that viewing assessment as an integral, rather than ‘extra’ aspect of student affairs and incorporating these activities within their work, student affairs professionals will not only improve the effectiveness of their work with students but also can help legitimise the field as a profession.Keywords: assessment, student affairs, best practices, higher educatio

Conserved Central Intraviral Protein Interactome of the Herpesviridae Family

Protein interactions are major driving forces behind the functional phenotypes of biological processes. As such, evolutionary footprints are reflected in system-level collections of protein-protein interactions (PPIs), i.e., protein interactomes. We conducted a comparative analysis of intraviral protein interactomes for representative species of each of the three subfamilies of herpesviruses (herpes simplex virus 1, human cytomegalovirus, and Epstein-Barr virus), which are highly prevalent etiologic agents of important human diseases. The intraviral interactomes were reconstructed by combining experimentally supported and computationally predicted protein-protein interactions. Using cross-species network comparison, we then identified family-wise conserved interactions and protein complexes, which we defined as a herpesviral “central” intraviral protein interactome. A large number of widely accepted conserved herpesviral protein complexes are present in this central intraviral interactome, encouragingly supporting the biological coherence of our results. Importantly, these protein complexes represent most, if not all, of the essential steps required during a productive life cycle. Hence the central intraviral protein interactome could plausibly represent a minimal infectious interactome of the herpesvirus family across a variety of hosts. Our data, which have been integrated into our herpesvirus interactomics database, HVint2.0, could assist in creating comprehensive system-level computational models of this viral lineage

Institutional Grants: Investing in Student Retention and Graduation

This study examines how institutional expenditures and grants (student financial aid) relate to retention and graduation. It looks at this relationship over a 10-year period and examines differences between institutions with low- and high-admissions selectivity standards. In general, expenditures for institutional grants positively contributed to retention and graduation rates except at high-selectivity institutions, where institutional grants did not significantly contribute to retention and graduation rates

Combining Information from Crosslinks and Monolinks in the Modeling of Protein Structures

Monolinks are produced in a chemical crosslinking mass spectrometry experiment and are more abundant than crosslinks. They convey residue exposure information, but so far have not been used in the modeling of protein structures. Here, we present the Monolink Depth Score (MoDS), for assessing structural models based on the depth of monolinked residues, corresponding to their distance to the nearest bulk water. Using simulated and reprocessed experimental data from the Proteomic Identification Database, we compare the performance of MoDS to MNXL, our previously developed score for assessing models based on crosslinking data. Our results show that MoDS can be used to effectively score models based on monolinks, and that a crosslink/monolink combined score (XLMO) leads to overall higher performance. The work strongly supports the use of monolink data in the context of integrative structure determination. We also present XLM-Tools, a program to assist in this effort, available at: https://github.com/Topf-Lab/XLM-Tools

Improved metrics for comparing structures of macromolecular assemblies determined by 3D electron-microscopy

Recent developments in 3-dimensional electron microcopy (3D-EM) techniques and a concomitant drive to look at complex molecular structures, have led to a rapid increase in the amount of volume data available for biomolecules. This creates a demand for better methods to analyse the data, including improved scores for comparison, classification and integration of data at different resolutions. To this end, we developed and evaluated a set of scoring functions that compare 3D-EM volumes. To test our scores we used a benchmark set of volume alignments derived from the Electron Microscopy Data Bank. We find that the performance of different scores vary with the map-type, resolution and the extent of overlap between volumes. Importantly, adding the overlap information to the local scoring functions can significantly improve their precision and accuracy in a range of resolutions. A combined score involving the local mutual information and overlap (LMI_OV) performs best overall, irrespective of the map category, resolution or the extent of overlap, and we recommend this score for general use. The local mutual information score itself is found to be more discriminatory than cross-correlation coefficient for intermediate-to-low resolution maps or when the map size and density distribution differ significantly. For comparing map surfaces, we implemented two filters to detect the surface points, including one based on the ‘extent of surface exposure’. We show that scores that compare surfaces are useful at low resolutions and for maps with evident surface features. All the scores discussed are implemented in TEMPy (http://tempy.ismb.lon.ac.uk/)

“I Don’t Just Give Tours”

Undergraduate student orientation leaders play a vital role in many new student orientation programs. Although the leaders assume many responsibilities, little is known about how these students benefit from this experience. This qualitative study examined what students learned from being student orientation leaders. Students’ learning occurred in four areas: intrapersonal growth, skill development, understanding of others, and understanding of the institution. Results of this study highlight the benefit of incorporating upper division leaders into orientation programs. In addition, it illustrates how new student programs provide a valuable experience for upper-division continuing students as well as new students in transition

Closing the gap – detection of clinically relevant von Willebrand disease in emergency settings through an improved algorithm based on rotational Thromboelastometry

Abstract Background Hemorrhage and blood loss are still among the main causes of preventable death. Global hemostatic assays are useful point-of-care test (POCT) devices to rapidly detect cumulative effects of plasma factors and platelets on coagulation. Thromboelastography (TEG) and Thromboelastometry (ROTEM) are established methods in many anesthesiological departments for guided hemostatic treatment. However, von Willebrand disease remains undetected by standard ROTEM, especially during emergency care, despite being the most prevalent congenital hemostatic disorder. Methods In our monocentric cohort pilot study we focused on hemostatic challenges associated with von Willebrand disease. Twenty-seven patients with suspected von Willebrand disease were included. We modified the routine ROTEM assay by adding a preincubation with ristocetin and commercially available plasma-derived von Willebrand factor to identify clinically relevant von Willebrand disease (VWD). Results Addition of von Willebrand factor to the ristocetin assay of a VWD type 3 patient restored the reaction of the whole blood probe to match the response of a healthy person. Our modified ROTEM assay with ristocetin (Ricotem) showed that all high responders (n = 7) had VWD. In the low responder group (n = 16) – 10 of 16 had VWD and in the normal responder group (n = 5), 2 of 5 had mild type 1 VWD. Conclusions This new modification of the standard ROTEM assay enables the detection of otherwise unnoticed critical von Willebrand disease based on alterations in clot formation and might serve as a novel approach to reliably assess severe VWD patients by platelet-mediated blood clotting in an emergency setting. We recommend incorporating this new VWD-focused screening tool into the current ROTEM-based management algorithm of acute microvascular bleeding

Refinement of atomic models in high resolution EM reconstructions using Flex-EM and local assessment

As the resolutions of Three Dimensional Electron Microscopic reconstructions of biological macromolecules are being improved, there is a need for better fitting and refinement methods at high resolutions and robust approaches for model assessment. Flex-EM/MODELLER has been used for flexible fitting of atomic models in intermediate-to-low resolution density maps of different biological systems. Here, we demonstrate the suitability of the method to successfully refine structures at higher resolutions (2.5–4.5 Å) using both simulated and experimental data, including a newly processed map of Apo-GroEL. A hierarchical refinement protocol was adopted where the rigid body definitions are relaxed and atom displacement steps are reduced progressively at successive stages of refinement. For the assessment of local fit, we used the SMOC (segment-based Manders’ overlap coefficient) score, while the model quality was checked using the Qmean score. Comparison of SMOC profiles at different stages of refinement helped in detecting regions that are poorly fitted. We also show how initial model errors can have significant impact on the goodness-of-fit. Finally, we discuss the implementation of Flex-EM in the CCP-EM software suite