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Better understanding of laboratory animal genetics will improve reproducibility.
No full textInconsistent characterization and reporting of laboratory animal genetics undermine research quality and reproducibility. We need to recognize the value of genetic characterization, improve training for researchers, and implement rigorous reporting standards
The normal bundle of a general canonical curve of genus at least 7 is semistable
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Local Value in the Television Archive: The Media Archive for Central England
No full textBritish television has in many ways been defined by competing visions of locality. Unlike American television, where local TV has often described small television stations, spatially bound to a city, suburb, or rural community, the ‘local’ in British television has largely been subsumed within the category of ‘the regional.’ When British television emerged in the 1930s, it was expressly national: centralized in London and operated by the BBC. In the 1950s, as transmitters were installed throughout the UK, concern grew over this centralization. With the arrival of commercial television in 1955, efforts were made to increase regional representation—to give voice to places, stories, and perspectives outside Britain’s cultural and economic center. However, UK’s broadcast regions did not emerge organically. They were instead determined by technology—their boundaries fixed by the geographical reach of transmitters—and by politics—so Wales, Scotland, and Northern Ireland could become regions just like the North or the Midlands. As such, the communities represented by these regions were vast, varied, and artificial. They included large cities, industrial towns, and rural farmlands. The programmes produced in these spaces were similarly diverse. Dramas, comedies, news, and magazine shows, set in distinct locations, representing unique communities, and broadcast to varying audiences all emerged under the somewhat clunky rubric of the ‘region.’ Different iterations of the local thus haunt these programmes, forming a fraught and almost accidental undercurrent of regional television.In this chapter, I seek to uncover the local within British regional television by turning to the archive, in particular the regional media archive—an institutional body explicitly concerned with collecting, preserving, and making accessible moving image material tied to specific territorial boundaries. Taking the Media Archive of Central England (MACE), whose remit concerns the moving image material of the Midlands, as my central case study, I explore the ways through which the regional media archive deconstructs the category of the broadcast region and articulates an alternative appraisal of televisual value, one in which locality is central. While regional television has included some of the UK’s most notable series, it has also embodied programming that falls outside the realm of national memory and popular consumption. It is these more niche programmes—the magazine series, quiz shows, and local news broadcasts rooted in the counties, cities, and towns that created them—that find their home in the regional media archive. By analyzing MACE’s collection, archival logic, and access initiatives, I examine how place and locality became central in the archive’s presentation of these often overlooked television programmes. They emerge as key components of their collecting practices and public engagements, breaking down the often artificial boundaries of regional television to return a more granular sense of place to the television housed within their walls. By removing television from its original broadcast context and repositioning it within the archive, I argue that MACE, and the regional media archive more generally, can serve as a space for the recovery of the ‘local’ in British television history.</p
A novel image segmentation method based on spatial autocorrelation identifies A-type potassium channel clusters in the thalamus
No full textUnsupervised segmentation in biological and non-biological images is only partially resolved. Segmentation either requires arbitrary thresholds or large teaching datasets. Here, we propose a spatial autocorrelation method based on Local Moran’s I coefficient to differentiate signal, background, and noise in any type of image. The method, originally described for geoinformatics, does not require a predefined intensity threshold or teaching algorithm for image segmentation and allows quantitative comparison of samples obtained in different conditions. It utilizes relative intensity as well as spatial information of neighboring elements to select spatially contiguous groups of pixels. We demonstrate that Moran’s method outperforms threshold-based method in both artificially generated as well as in natural images especially when background noise is substantial. This superior performance can be attributed to the exclusion of false positive pixels resulting from isolated, high intensity pixels in high noise conditions. To test the method’s power in real situation, we used high power confocal images of the somatosensory thalamus immunostained for Kv4.2 and Kv4.3 (A-type) voltage-gated potassium channels in mice. Moran’s method identified high-intensity Kv4.2 and Kv4.3 ion channel clusters in the thalamic neuropil. Spatial distribution of these clusters displayed strong correlation with large sensory axon terminals of subcortical origin. The unique association of the special presynaptic terminals and a postsynaptic voltage-gated ion channel cluster was confirmed with electron microscopy. These data demonstrate that Moran’s method is a rapid, simple image segmentation method optimal for variable and high noise conditions
Wnt/GSK‐3β mediates posttranslational modifications of FLYWCH1 to regulate intestinal epithelial function and tumorigenesis in the colon
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Characterizing the evolutionary dynamics of cancer proliferation in single-cell clones with SPRINTER
No full textProliferation is a key hallmark of cancer, but whether it differs between evolutionarily distinct clones co-existing within a tumor is unknown. We introduce the Single-cell Proliferation Rate Inference in Non-homogeneous Tumors through Evolutionary Routes (SPRINTER) algorithm that uses single-cell whole-genome DNA sequencing data to enable accurate identification and clone assignment of S- and G2-phase cells, as assessed by generating accurate ground truth data. Applied to a newly generated longitudinal, primary-metastasis-matched dataset of 14,994 non-small cell lung cancer cells, SPRINTER revealed widespread clone proliferation heterogeneity, orthogonally supported by Ki-67 staining, nuclei imaging and clinical imaging. We further demonstrated that high-proliferation clones have increased metastatic seeding potential, increased circulating tumor DNA shedding and clone-specific altered replication timing in proliferation- or metastasis-related genes associated with expression changes. Applied to previously generated datasets of 61,914 breast and ovarian cancer cells, SPRINTER revealed increased single-cell rates of different genomic variants and enrichment of proliferation-related gene amplifications in high-proliferation clones
Staging the Ghost Story
No full textThis monograph takes as its focus the relationship between the theatre and the ghost story, that is, tales of the supernatural as narrative itself takes centre stage. The ghost story on stage has not been subject to any past historical study, which is remarkable when the genre itself raises pertinent questions about the relationship between representation and liveness, the limits of the natural in the theatre (and stage naturalism), the challenges of embodiment, theatrical effect and structure, and the power of storytelling. Moreover, it asks us to consider the importance of the theatrical medium itself in the dissemination of the ghost story.</p
Subclonal immune evasion in non-small cell lung cancer.
No full textCancers rarely respond completely to immunotherapy. While tumors consist of multiple genetically distinct clones, whether this affects the potential for immune escape remains unclear due to an inability to isolate and propagate individual subclones from human cancers. Here, we leverage the multi-region TRACERx lung cancer evolution study to generate a patient-derived organoid - T cell co-culture platform that allows the functional analysis of subclonal immune escape at single clone resolution. We establish organoid lines from 11 separate tumor regions from three patients, followed by isolation of 81 individual clonal sublines. Co-culture with tumor infiltrating lymphocytes (TIL) or natural killer (NK) cells reveals cancer-intrinsic and subclonal immune escape in all 3 patients. Immune evading subclones represent genetically distinct lineages with a unique evolutionary history. This indicates that immune evading and non-evading subclones can be isolated from the same tumor, suggesting that subclonal tumor evolution directly affects immune escape
Lost in Translation: Navigating the Path from Bench to Bioimage Analysis
No full textModern microscopy produces datasets that are increasingly large and complex, yet many biologists lack the computational skills needed to analyse them efficiently. This mismatch increases the divide between experimental and analytical work, creating inconsistent workflows. As a result, key steps often become “black boxes”, with poor documentation and processing that undermines reproducibility. Communication barriers further slow progress and lead to misaligned expectations. Closing this gap is essential to achieving trustworthy biological insights and strengthening the reproducibility and impact of research in the life sciences.</p
Combining assessment methods to gain new insights into SMLM reconstruction accuracy
No full textSingle Molecule Localisation Microscopy (SMLM) has become a common method in Bio-imaging. Despite most users being increasingly aware that factors other than the localisation precision (such as bias/artefacts) contribute to resolution, a universal way of assessing reconstruction quality does not yet exist.Currently the three most effective tools for assessing SMLM images are HAWKMAN, SQUIRREL and FRC, each assessing different aspects of the reconstruction.However, the results of these tools can be interdependent, complicating the assessment of reconstruction quality. Here we demonstrate a method and a software tool that in corporates slightly modified versions of these techniques into a combined assessment of reconstruction quality and resolution.Poster presented as part of the Crick BioImage Analysis Symposium 2025.Permission has been given by authors to upload to Crick Figshare. Copyright remains with the original authors.</p