Polymorphism in the innate immune receptor SIRPα controls CD47 binding and autoimmunity in the nonobese diabetic mouse.

The signal regulatory protein (SIRP) locus encodes a family of paired receptors that mediate both activating and inhibitory signals and is associated with type 1 diabetes (T1D) risk. The NOD mouse model recapitulates multiple features of human T1D and enables mechanistic analysis of the impact of genetic variations on disease. In this study, we identify Sirpa encoding an inhibitory receptor on myeloid cells as a gene in the insulin-dependent diabetes locus 13.2 (Idd13.2) that drives islet inflammation and T1D. Compared to T1D-resistant strains, the NOD variant of SIRPα displayed greater binding to its ligand CD47, as well as enhanced T cell proliferation and diabetogenic potency. Myeloid cell-restricted expression of a Sirpa transgene accelerated disease in a dose-dependent manner and displayed genetic and functional interaction with the Idd5 locus to potentiate insulitis progression. Our study demonstrates that variations in both SIRPα sequence and expression level modulate T1D immunopathogenesis. Thus, we identify Sirpa as a T1D risk gene and provide insight into the complex mechanisms by which disease-associated variants act in concert to drive defined stages in disease progression

Polymorphism in the innate immune receptor SIRPα controls CD47 binding and autoimmunity in the nonobese diabetic mouse.

The signal regulatory protein (SIRP) locus encodes a family of paired receptors that mediate both activating and inhibitory signals and is associated with type 1 diabetes (T1D) risk. The NOD mouse model recapitulates multiple features of human T1D and enables mechanistic analysis of the impact of genetic variations on disease. In this study, we identify Sirpa encoding an inhibitory receptor on myeloid cells as a gene in the insulin-dependent diabetes locus 13.2 (Idd13.2) that drives islet inflammation and T1D. Compared to T1D-resistant strains, the NOD variant of SIRPα displayed greater binding to its ligand CD47, as well as enhanced T cell proliferation and diabetogenic potency. Myeloid cell-restricted expression of a Sirpa transgene accelerated disease in a dose-dependent manner and displayed genetic and functional interaction with the Idd5 locus to potentiate insulitis progression. Our study demonstrates that variations in both SIRPα sequence and expression level modulate T1D immunopathogenesis. Thus, we identify Sirpa as a T1D risk gene and provide insight into the complex mechanisms by which disease-associated variants act in concert to drive defined stages in disease progression

The impact of correction on MP2RAGE

Determination of cortical thickness using MRI has often been criticized due to the presence of various error sources. Specifically, anatomical MRI relying on T1 contrast may be unreliable due to spatially variable image contrast between gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF). Especially at ultra-high field (≥ 7T) MRI, transmit and receive B1 -related image inhomogeneities can hamper correct classification of tissue types. In the current paper, we demonstrate that residual B1+ (transmit) inhomogeneities in the T1 -weighted and quantitative T1 images using the MP2RAGE sequence at 7T lead to biases in cortical thickness measurements. As expected, post-hoc correction for the spatially varying B1+ profile reduced the apparent T1 values across the cortex in regions with low B1+, and slightly increased apparent T1 in regions with high B1+. As a result, improved contrast-to-noise ratio both at the GM-CSF and GM-WM boundaries can be observed leading to more accurate surface reconstructions and cortical thickness estimates. Overall, the changes in cortical thickness ranged between a 5% decrease to a 70% increase after B1+ correction, reducing the variance of cortical thickness values across the brain dramatically and increasing the comparability with normative data. More specifically, the cortical thickness estimates increased in regions characterized by a strong decrease of apparent T1 after B1+ correction in regions with low B1+ due to improved detection of the pial surface. The current results suggest that cortical thickness can be more accurately determined using MP2RAGE data at 7T if B1+ inhomogeneities are accounted for

duecredit/duecredit: 0.9.2

Bug Fix Tell LGTM to ignore unused imports in stub.py #179 (@jwodder) Internal Make Debian Python version PEP440 compliant #184 (@bdrung) Authors: 2 Benjamin Drung (@bdrung) John T. Wodder II (@jwodder

duecredit/duecredit: 0.9.3

<h4> Bug Fix</h4> <ul> <li>ENH: codespell <a href="https://github.com/duecredit/duecredit/pull/185">#185</a> (<a href="https://github.com/yarikoptic">@yarikoptic</a>)</li> </ul> <h4> Internal</h4> <ul> <li>RF: remove remaining usage of SIX, and thus move away fully from Python 2 <a href="https://github.com/duecredit/duecredit/pull/186">#186</a> (<a href="https://github.com/a-detiste">@a-detiste</a> <a href="https://github.com/yarikoptic">@yarikoptic</a>)</li> <li>Ignore "vor" which is now detected as typo <a href="https://github.com/duecredit/duecredit/pull/186">#186</a> (<a href="https://github.com/yarikoptic">@yarikoptic</a>)</li> </ul> <h4> Tests</h4> <ul> <li>Use teardown_method instead of nose-y teardown <a href="https://github.com/duecredit/duecredit/pull/190">#190</a> (<a href="https://github.com/yarikoptic">@yarikoptic</a>)</li> <li>Move from Travis to github workflow, disable coveralls <a href="https://github.com/duecredit/duecredit/pull/187">#187</a> (<a href="https://github.com/yarikoptic">@yarikoptic</a>)</li> </ul> <h4>Authors: 2</h4> <ul> <li>Alexandre Detiste (<a href="https://github.com/a-detiste">@a-detiste</a>)</li> <li>Yaroslav Halchenko (<a href="https://github.com/yarikoptic">@yarikoptic</a>)</li> </ul&gt

Proceedings of the OHBM Brainhack 2021

The global pandemic presented new challenges and op-portunities for organizing conferences, and OHBM 2021was no exception. The OHBM Brainhack is an event thatoccurs just prior to the OHBM meeting, typically in-per-son, where scientists of all levels of expertise and interestgather to work and learn together for a few days in a col-laborative hacking-style environment on projects of com-mon interest (1). Building off the success of the OHBM2020 Hackathon (2), the 2021 Open Science SpecialInterest Group came together online to organize a largecoordinated Brainhack event that would take place overthe course of 4 days. The OHBM 2021 Brainhack eventwas organized along two guiding principles, providinga highly inclusive collaborative environment for inter-action between scientists across disciplines and levelsof expertise to push forward important projects thatneed support, also known as the “Hack-Track” of theBrainhack. The second aim of the OHBM Brainhack is toempower scientists to improve the quality of their sci-entific endeavors by providing high-quality hands-ontraining on best practices in open-science approaches.This is best exemplified by the training events providedby the “Train-Track” at the OHBM 2021 Brainhack. Here,we briefly explain both of these elements of the OHBM2021 Brainhack, before continuing on to the Brainhackproceedings

Proceedings of the OHBM Brainhack 2022

International audienceOHBM Brainhack 2022 took place in June 2022. The first hybrid OHBM hackathon, it had an in-person component taking place in Glasgow and three hubs around the globe to improve inclusivity and fit as many timezones as possible. In the buzzing setting of the Queen Margaret Union and of the virtual platform, 23 projects were presented for development. Following are the reports of 14 of those, as well as a recapitulation of the organisation of the event