What do we (not) know about research software engineering?

As recognition of the vital importance of software for contemporary research is increasing, Research Software Engineering (RSE) is emerging as a discipline in its own right. We present an inventory of relevant research questions about RSE as a basis for future research and initiatives to advance the field, highlighting selected literature and initiatives. This work is the outcome of a RSE community workshop held as part of the 2020 International Series of Online Research Software Events (SORSE) which identified and prioritized key questions across three overlapping themes: people, policy and infrastructure. Almost half of the questions focus on the people theme, which addresses issues related to career paths, recognition and motivation; recruitment and retention; skills; and diversity, equity and inclusion. However, the people and policy themes have the same number of prioritized questions. We recommend that different types of stakeholders, such as RSE employers and policy makers, take responsibility for supporting or encouraging answering of these questions by organizations that have an interest. Initiatives such as the International Council of RSE Associations should also be engaged in this work

What Do We (Not) Know About Research Software Engineering?

As recognition of the vital importance of software for contemporary research is increasing, Research Software Engineering (RSE) is emerging as a discipline in its own right. We present an inventory of relevant research questions about RSE as a basis for future research and initiatives to advance the field, highlighting selected literature and initiatives. This work is the outcome of a RSE community workshop held as part of the 2020 International Series of Online Research Software Events (SORSE) which identified and prioritized key questions across three overlapping themes: people, policy and infrastructure. Almost half of the questions focus on the people theme, which addresses issues related to career paths, recognition and motivation; recruitment and retention; skills; and diversity, equity and inclusion. However, the people and policy themes have the same number of prioritized questions. We recommend that different types of stakeholders, such as RSE employers and policy makers, take responsibility for supporting or encouraging answering of these questions by organizations that have an interest. Initiatives such as the International Council of RSE Associations should also be engaged in this work

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

A new class of supramolecular ligands stabilizes 14-3-3 protein-protein interactions by up to two orders of magnitude

\u3cp\u3eWe report the first supramolecular stabilizers of the interaction between 14-3-3ζ and two of its effectors, Tau and C-Raf, which are involved in neurodegenerative diseases and proliferative signal transduction, respectively. These supramolecular ligands open up an opportunity to modulate functions of 14-3-3 with these effectors.\u3c/p\u3

Computational model predicts protein binding sites of a luminescent ligand equipped with guanidiniocarbonyl-pyrrole groups

The 14-3-3 protein family, one of the first discovered phosphoserine/phosphothreonine binding proteins, has attracted interest not only because of its important role in the cell regulatory processes but also due to its enormous number of interactions with other proteins. Here, we use a computational approach to predict the binding sites of the designed hybrid compound featuring aggregation-induced emission luminophores as a potential supramolecular ligand for 14-3-3ζ in the presence and absence of C-Raf peptides. Our results suggest that the area above and below the central pore of the dimeric 14-3-3ζ protein is the most probable binding site for the ligand. Moreover, we predict that the position of the ligand is sensitive to the presence of phosphorylated C-Raf peptides. With a series of experiments, we confirmed the computational prediction of two C2 related, dominating binding sites on 14-3-3ζ that may bind to two of the supramolecular ligand molecules

Rational design, binding studies and crystal structure evaluation of the first ligand targeting the dimerization Interface of the 14-3-3ζ adapter protein

14-3-3 Proteins play a central role in signalling pathways in cells: they interact as gatekeeper proteins with a huge number of binding partners. Their function as hub for intracellular communication can explain why these adapter proteins are associated with a wide range of diseases. How they control the various cellular mechanisms is still unclear, but it is assumed that the dimeric nature of the 14-3-3 proteins plays a key role in their activity. Here, we present, to the best of our knowledge, the first example of a small molecule binding to the 14-3-3ζ dimerisation interface. This compound was designed by rational in silico optimisation of a peptidic ligand identified from biochemical screening of a peptidic library, and the binding was characterised by UV/Vis spectroscopy, microscale thermophoresis, multiscale simulations, and X-ray crystallography

Rational design, binding studies and crystal structure evaluation of the first ligand targeting the dimerization Interface of the 14-3-3ζ adapter protein

\u3cp\u3e14-3-3 Proteins play a central role in signalling pathways in cells: they interact as gatekeeper proteins with a huge number of binding partners. Their function as hub for intracellular communication can explain why these adapter proteins are associated with a wide range of diseases. How they control the various cellular mechanisms is still unclear, but it is assumed that the dimeric nature of the 14-3-3 proteins plays a key role in their activity. Here, we present, to the best of our knowledge, the first example of a small molecule binding to the 14-3-3ζ dimerisation interface. This compound was designed by rational in silico optimisation of a peptidic ligand identified from biochemical screening of a peptidic library, and the binding was characterised by UV/Vis spectroscopy, microscale thermophoresis, multiscale simulations, and X-ray crystallography.\u3c/p\u3