The generation of biologically active proteins by regulated intramembrane proteolysis is a highly conserved mechanism in cell signaling. Presenilin-dependent ␥-secretase activity is responsible for the intramembrane proteolysis of selected type I membrane proteins, including ␤-amyloid precursor protein (APP) and Notch. A small fraction of intracellular domains derived from both APP and Notch translocates to and appears to function in the nucleus, suggesting a generic role for ␥-secretase cleavage in nuclear signaling. Here we show that the p75 neurotrophin receptor (p75 NTR ) undergoes presenilin-dependent intramembrane proteolysis to yield the soluble p75-intracellular domain. The p75 NTR is a multifunctional type I membrane protein that promotes neurotrophininduced neuronal survival and differentiation by forming a heteromeric co-receptor complex with the Trk receptors. Mass spectrometric analysis revealed that ␥-secretase-mediated cleavage of p75 NTR occurs at a position located in the middle of the transmembrane (TM) domain, which is reminiscent of the amyloid ␤-peptide 40 (A␤40) cleavage of APP and is topologically distinct from the major TM cleavage site of Notch 1. Size exclusion chromatography and co-immunoprecipitation analyses revealed that TrkA forms a molecular complex together with either full-length p75 or membrane-tethered C-terminal fragments. The p75-ICD was not recruited into the TrkAcontaining high molecular weight complex, indicating that ␥-secretase-mediated removal of the p75 TM domain may perturb the interaction with TrkA. Independent of the possible nuclear function, our studies suggest that ␥-secretase-mediated p75 NTR proteolysis plays a role in the formation/disassembly of the p75-TrkA receptor complex by regulating the availability of the p75 TM domain that is required for this interaction.The p75 neurotrophin receptor (p75 NTR

Summary Background Centrosome orientation toward the leading edge of migrating cells depends on dynein and microtubules (MTs) and as well on a number of signaling factors at the leading edge. However, centrosomes are maintained at the cell center during orientation in fibroblasts suggesting that factors working at sites other than the leading edge may also be involved. Results In a search for factors that function with dynein in centrosome orientation, we found that the polarity protein Par3 associated with dynein and that knockdown of Par3 inhibited centrosome orientation by disrupting the position of the centrosome at the cell center, the same phenotype as that observed with dynein inhibition. Par3 associated with dynein through its N-terminal dimerization and PDZ1 domains, and interacted specifically with dynein light intermediate chain 2 (LIC2). siRNA knockdown of LIC2, but not LIC1, or overexpression of LIC2 or the N-terminal domain of Par3, also inhibited centrosome orientation by disrupting centrosome position. Par3 specifically localized to cell-cell contacts in wound-edge fibroblasts where it overlapped with MT ends and dynein puncta in a LIC2 dependent fashion. Live imaging showed that MTs exhibited increased pausing at cell-cell contacts compared to the leading edge and that this elevated pausing was dependent on Par3 and LIC2. Conclusion Par3 associates with dynein and contributes to the local regulation of MT dynamics at cell-cell contacts and proper positioning of the centrosome at the cell center. We propose that Par3 acts as a cortical factor that tethers MTs through its association with LIC2-dynein.

How cytoplasmic dynein is recruited to diverse organelles remains incompletely understood. Using the first subcellular localization of LIC isoforms, along with RNAi, RILP, and dynactin dominant negatives, the LIC subunits are found to recruit dynein specifically to components of the late endocytic pathway through a dynactin-independent mechanism.

A central tenet in support of research reproducibility is the ability to uniquely identify research resources, i.e., reagents, tools, and materials that are used to perform experiments. However, current reporting practices for research resources are insufficient to identify the exact resources that are reported or to answer basic questions such as "How did other studies use resource X?" To address this issue, the Resource Identification Initiative was launched as a pilot project to improve the reporting standards for research resources in the Methods sections of articles and thereby improve identifiability and scientific reproducibility. The pilot engaged over 25 biomedical journal editors from most major publishers, as well as scientists and funding officials. Authors were asked to include Research Resource Identifiers (RRIDs) in their articles prior to publication for three resource types: antibodies, model organisms, and tools (i.e., software and databases). RRIDs are assigned by an authoritative database, for example, a model organism database for each type of resource. To make it easier for authors to obtain RRIDs, resources were aggregated from the appropriate databases and their RRIDs made available in a central Web portal (http://scicrunch.org/resources). RRIDs meet three key criteria: they are machine-readable, free to generate and access, and are consistent across publishers and journals. The pilot was launched in February of 2014 and over 300 articles have appeared that report RRIDs. The number of journals participating has expanded from the original 25 to more than 40, with RRIDs appearing in 62 different journals to date. Here we present an overview of the pilot project and its outcomes to date. We show that authors are able to identify resources and are supportive of the goals of the project. Identifiability of the resources post-pilot showed a dramatic improvement for all three resource types, suggesting that the project has had a significant impact on identifiability of research resources.

A central tenet in support of research reproducibility is the ability to uniquely identify research resources, i.e., reagents, tools, and materials that are used to perform experiments. However, current reporting practices for research resources are insufficient to allow humans and algorithms to identify the exact resources that are reported or answer basic questions such as "What other studies used resource X?" To address this issue, the Resource Identification Initiative was launched as a pilot project to improve the reporting standards for research resources in the methods sections of papers and thereby improve identifiability and reproducibility. The pilot engaged over 25 biomedical journal editors from most major publishers, as well as scientists and funding officials. Authors were asked to include Research Resource Identifiers (RRIDs) in their manuscripts prior to publication for three resource types: antibodies, model organisms, and tools (including software and databases). RRIDs represent accession numbers assigned by an authoritative database, e.g., the model organism databases, for each type of resource. To make it easier for authors to obtain RRIDs, resources were aggregated from the appropriate databases and their RRIDs made available in a central web portal ( ). RRIDs meet three key criteria: they are www.scicrunch.org/resources machine readable, free to generate and access, and are consistent across publishers and journals. , 4:134 Last updated: 23 JAN 2019 300 papers have appeared that report RRIDs. The number of journals participating has expanded from the original 25 to more than 40. Here, we present an overview of the pilot project and its outcomes to date. We show that authors are generally accurate in performing the task of identifying resources and supportive of the goals of the project. We also show that identifiability of the resources pre-and post-pilot showed a dramatic improvement for all three resource types, suggesting that the project has had a significant impact on reproducibility relating to research resources.

A central tenet in support of research reproducibility is the ability to uniquely identify research resources, that is, reagents, tools, and materials that are used to perform experiments. However, current reporting practices for research resources are insufficient to identify the exact resources that are reported or to answer basic questions such as “How did other studies use resource X?” To address this issue, the Resource Identification Initiative was launched as a pilot project to improve the reporting standards for research resources in the methods sections of papers and thereby improve identifiability and scientific reproducibility. The pilot engaged over 25 biomedical journal editors from most major publishers, as well as scientists and funding officials. Authors were asked to include Research Resource Identifiers (RRIDs) in their manuscripts prior to publication for three resource types: antibodies, model organisms, and tools (i.e., software and databases). RRIDs are assigned by an authoritative database, for example, a model organism database for each type of resource. To make it easier for authors to obtain RRIDs, resources were aggregated from the appropriate databases and their RRIDs made available in a central web portal ( http://scicrunch.org/resources). RRIDs meet three key criteria: they are machine readable, free to generate and access, and are consistent across publishers and journals. The pilot was launched in February of 2014 and over 300 papers have appeared that report RRIDs. The number of journals participating has expanded from the original 25 to more than 40 with RRIDs appearing in 62 different journals to date. Here, we present an overview of the pilot project and its outcomes to date. We show that authors are able to identify resources and are supportive of the goals of the project. Identifiability of the resources post‐pilot showed a dramatic improvement for all three resource types, suggesting that the project has had a significant impact on identifiability of research resources.

A central tenet in support of research reproducibility is the ability to uniquely identify research resources, i.e., reagents, tools, and materials that are used to perform experiments. However, current reporting practices for research resources are insufficient to allow humans and algorithms to identify the exact resources that are reported or answer basic questions such as “What other studies used resource X?” To address this issue, the Resource Identification Initiative was launched as a pilot project to improve the reporting standards for research resources in the methods sections of papers and thereby improve identifiability and reproducibility. The pilot engaged over 25 biomedical journal editors from most major publishers, as well as scientists and funding officials. Authors were asked to include Research Resource Identifiers (RRIDs) in their manuscripts prior to publication for three resource types: antibodies, model organisms, and tools (including software and databases). RRIDs represent accession numbers assigned by an authoritative database, e.g., the model organism databases, for each type of resource. To make it easier for authors to obtain RRIDs, resources were aggregated from the appropriate databases and their RRIDs made available in a central web portal ( www.scicrunch.org/resources). RRIDs meet three key criteria: they are machine readable, free to generate and access, and are consistent across publishers and journals. The pilot was launched in February of 2014 and over 300 papers have appeared that report RRIDs. The number of journals participating has expanded from the original 25 to more than 40. Here, we present an overview of the pilot project and its outcomes to date. We show that authors are generally accurate in performing the task of identifying resources and supportive of the goals of the project. We also show that identifiability of the resources pre- and post-pilot showed a dramatic improvement for all three resource types, suggesting that the project has had a significant impact on reproducibility relating to research resources.

Aim: We wanted to learn how the Registered Report article format was working for key stakeholder groups at the publisher Wiley.Methods: We surveyed editors, peer reviewers and authors via email with a link to a survey in Microsoft Forms. Quantitative and qualitative feedback was collected and assessed.Results: Authors and peer reviewers are very positive about their experience with Registered Reports. Editors are supportive of the initiative but highlight lack of submissions as their main challenge. Editors and authors would welcome the use of article badges as indicators of Registered Reports.Conclusion: The Registered Reports initiative is gaining support from across disciplines. However, more effort is needed to incentivise submissions of Registered Reports across journals.