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Abbott, H.

Publications and source records attributed to Abbott, H..

4 recordsLinked to original sources

SynthMLM: A framework for interpretable analysis and synthetic localisation data generation for SMLM

Quantitative analysis of single-molecule localisation microscopy (SMLM) data remains challenging because biologically diverse, well-annotated datasets are limited, whilst nanoscale protein organisation is heterogeneous and difficult to describe with hand-tuned metrics. We present SynthMLM, a framework that infers interpretable structural descriptors from experimental SMLM data and uses these descriptors to generate synthetic localisation datasets. We demonstrate SynthMLM by generating descriptor-matched synthetic datasets corresponding to diverse experimental SMLM datasets and evaluating their agreement with real data using descriptor-level and embedding-based measures. By enabling controlled generation of synthetic localisation data, SynthMLM provides a practical resource for benchmarking SMLM analysis methods, testing algorithm failure modes, and developing machine-learning workflows where large, labelled datasets are required.

biophysics↗

Mycobacterium tuberculosis-specific CD4 T cells expressing transcription factors associate with bacterial control in granulomas

Despite the extensive research on CD4 T cells within the context of Mycobacterium tuberculosis (Mtb) infection, few studies have focused on identifying and investigating the profile of Mtb-specific T cells within lung granulomas. To facilitate identification of Mtb-specific CD4 T cells, we identified immunodominant epitopes for two Mtb proteins, Rv1196 and Rv0125, using a Mauritian cynomolgus macaque model of Mtb infection, providing data for the synthesis of MHC Class II tetramers. Using tetramers, we identified Mtb-specific cells within different immune compartments post-infection. We found that granulomas were enriched sites for Mtb-specific cells and that tetramer+ cells had increased frequencies of the activation marker CD69, and transcription factors T-bet and ROR{gamma}T, compared to tetramer negative cells within the same sample. Our data revealed that while the frequency of Rv1196 tetramer+ cells was positively correlated with granuloma bacterial burden, the frequency of ROR{gamma}T or T-bet within tetramer+ cells was inversely correlated with granuloma bacterial burden highlighting the importance of having activated, functional Mtb-specific cells for control of Mtb in lung granulomas.

immunology↗

The mouse Balbiani body maintains primordial follicle quiescence via RNA storage

In mammalian females, the transition between quiescent primordial follicles and follicular development is critical for maintaining ovarian function and reproductive longevity. In primary oocytes of mouse quiescent primordial follicles, Golgi complexes are organized into a spherical structure, the Balbiani body. Here, we show that the structure of the B-body is maintained by microtubules and actin. The B-body stores mRNA-capping enzyme and 597 mRNAs associated with mRNA-decapping enzyme 1A. Proteins encoded by these mRNAs function in enzyme binding, cellular component organization and packing of telomere ends. Pharmacological disassembly of the B-body triggers translation of stored mRNAs and activates primordial follicles in culture and in vivo mouse model. Thus, primordial follicle quiescence is maintained by the B-body, and translationally inactive B-body-stored mRNAs may be regulated by 5-capping.

cell biology↗

Altered germline cyst and oocyte differentiation in Tex14 mutant mice reveal a new mechanism underlying female reproductive life-span

In adult mammalian females, primordial follicles that form in the fetal/neonatal ovary are the only source to sustain adult ovarian function. Our previous studies revealed that during oocyte differentiation and primordial follicle formation in mouse fetal ovaries, primary oocytes form via gaining cytoplasm and organelles from sister germ cells that are connected to them by intercellular bridges within germline cysts. To better understand the role of intercellular bridges in oocyte differentiation, we analyzed mutant females lacking testis-expressed 14 (Tex14), a gene involved in cytokinesis and bridge formation. In Tex14-/- fetal ovaries, germ cells divide to form a reduced number of cysts in which sister germ cells are still connected via syncytia or fragmented cell membranes, rather than normal intercellular bridges. Compared with wildtype cysts, Tex14-/- cysts fragment at a higher frequency and produce a greatly reduced number of primary oocytes with highly precocious cytoplasmic enrichment and enlarged volume. By contrast, Tex14+/- germline cysts are less fragmented and generate primary oocytes that are smaller than wild type. Interestingly, enlarged Tex14-/- primary oocytes are much more stable than wild type oocytes and more efficiently sustain folliculogenesis, whereas undersized Tex14+/- primary oocytes turn over at an accelerated rate. Our observations directly link the nature of fetal germ cell connectivity to cytoplasmic enrichment during oocyte differentiation and to oocyte developmental potential in the adult ovary. Our results imply that the duration of adult ovarian function is strongly influenced by the number of primary oocytes acquiring highly enriched cytoplasm during oocyte differentiation in fetal ovaries, rather than just by the size of the primordial follicle pool.

developmental biology↗