6 research outputs found
Topologically faithful image segmentation via induced matching of persistence barcodes
Image segmentation is a largely researched field where neural networks find
vast applications in many facets of technology. Some of the most popular
approaches to train segmentation networks employ loss functions optimizing
pixel-overlap, an objective that is insufficient for many segmentation tasks.
In recent years, their limitations fueled a growing interest in topology-aware
methods, which aim to recover the correct topology of the segmented structures.
However, so far, none of the existing approaches achieve a spatially correct
matching between the topological features of ground truth and prediction.
In this work, we propose the first topologically and feature-wise accurate
metric and loss function for supervised image segmentation, which we term Betti
matching. We show how induced matchings guarantee the spatially correct
matching between barcodes in a segmentation setting. Furthermore, we propose an
efficient algorithm to compute the Betti matching of images. We show that the
Betti matching error is an interpretable metric to evaluate the topological
correctness of segmentations, which is more sensitive than the well-established
Betti number error. Moreover, the differentiability of the Betti matching loss
enables its use as a loss function. It improves the topological performance of
segmentation networks across six diverse datasets while preserving the
volumetric performance. Our code is available in
https://github.com/nstucki/Betti-matching
Nucleotide excision repair–induced H2A ubiquitination is dependent on MDC1 and RNF8 and reveals a universal DNA damage response
The epigenetic mark indicative of DNA UV damage or double-strand breaks is achieved via a common pathway regardless of the cause of damage
Impaired mTORC1-Dependent Expression of Homer-3 Influences SCA1 Pathophysiology.
Spinocerebellar ataxia type 1 (SCA1), due to the expansion of a polyglutamine repeat within the ubiquitously expressed Ataxin-1 protein, leads to the premature degeneration of Purkinje cells (PCs), the cause of which is poorly understood. Here, we identified the unique proteomic signature of Sca1(154Q/2Q) PCs at an early stage of disease, highlighting extensive alterations in proteins associated with synaptic functioning, maintenance, and transmission. Focusing on Homer-3, a PC-enriched scaffold protein regulating neuronal activity, revealed an early decline in its expression. Impaired climbing fiber-mediated synaptic transmission diminished mTORC1 signaling, paralleling Homer-3 reduction in Sca1(154Q/2Q) PCs. Ablating mTORC1 within PCs or pharmacological inhibition of mTORC1 identified Homer-3 as its downstream target. mTORC1 knockout in Sca1(154Q/2Q) PCs exacerbated and accelerated pathology. Reinstating Homer-3 expression in Sca1(154Q/2Q) PCs attenuated cellular dysfunctions and improved motor deficits. Our work reveals that impaired mTORC1-Homer-3 activity underlies PC susceptibility in SCA1 and presents a promising therapeutic target
The AAA-ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double-strand breaks
The accumulation of the human tumor suppressor 53BP1 at DNA damage sites requires the ubiquitin ligases RNF8 and RNF168. As 53BP1 recognizes dimethylated Lys20 in histone H4 (H4K20me2), the requirement for RNF8- and RNF168-mediated ubiquitylation has been unclear. Here we show that RNF8-mediated ubiquitylation facilitates the recruitment of the AAA-ATPase valosin-containing protein (VCP, also known as p97) and its cofactor NPL4 to sites of double-strand breaks. RIDDLE cells, which lack functional RNF168, also show impaired recruitment of VCP to DNA damage. The ATPase activity of VCP promotes the release of the Polycomb protein L3MBTL1 from chromatin, which also binds the H4K20me2 histone mark, thereby facilitating 53BP1 recruitment. Consistent with this, nematodes lacking the VCP orthologs CDC-48.1 or CDC-48.2, or cofactors UFD-1 or NPL-4, are highly sensitive to ionizing radiation. Our data suggest that human RNF8 and RNF168 promote VCP-mediated displacement of L3MBTL1 to unmask 53BP1 chromatin binding sites