Biology subjects

Calabrese, E.

Publications and source records attributed to Calabrese, E..

7 recordsLinked to original sources

bioRxiv2026

NeCS-Flow: Necrosis-Guided Contrast-Enhanced MRI Synthesis with Rectified-Flow Refinement

Background: Gadolinium-based contrast agents raise concerns about tissue deposition, adverse reactions, and increased costs. Purpose: To develop and validate a deep learning pipeline for gadolinium-free post-contrast T1w brain MRI synthesis incorporating necrotic scaling and Posterior-Mean Rectified Flow (PMRF) refinement, and to evaluate diagnostic utility through a blinded multi-reader study. Study Type: Retrospective. Population: 454 patients with adult-type gliomas (grade 2-4) from four publicly available datasets. Training used 374 patients; internal testing used 60 held-out patients; external validation used 20 patients. Field Strength/Sequence: 1.5-3.0 T; pre-contrast T1w, T2w, and FLAIR as inputs; post-contrast T1w as synthesis target. Assessment: A three-stage pipeline comprising nnU-Net Necrotic core segmentation, necrotic-scaling-guided U-Net Contrast Synthesis, and PMRF perceptual refinement (NeCS-Flow) was evaluated using whole-brain and tumor-region similarity metrics, enhancing tumor Dice scores, perceptual quality metrics, and a blinded three-reader study assessing diagnostic accuracy, enhancement detection, image quality, and real-versus-synthetic discriminability. Statistical Tests: Paired t-tests and two one-sided tests for model comparison; Fisher's exact test and two-sample t-tests for reader study comparisons, with p < 0.05 considered significant. Results: Necrotic scaling consistently improved real versus synthetic enhancing tumor Dice internally (HGG: 0.793 to 0.816) and externally (HGG: 0.465 to 0.612). NeCS-Flow outperformed two benchmark architectures on all quantitative metrics in internal and external testing, although absolute enhancing tumor accuracy declined for all models on the external cohort. PMRF refinement improved perceptual realism across both tumor types, reducing both FID and KID. Readers distinguished synthetic from real images only modestly above chance (overall accuracy 61.7%), and no significant differences between real and synthetic images were found for any clinical metric. Data Conclusion: NeCS-Flow synthesizes perceptually realistic and diagnostically equivalent post-contrast T1w brain MRI, with necrotic scaling improving enhancing tumor delineation and PMRF refinement improving perceptual realism across gliomas. Performance on an external cohort was preserved relative to benchmark methods, though reduced in absolute terms.

bioinformatics↗

bioRxiv2026

Timing of DNA damage checkpoint adaptation predicts post-mitotic proliferative competence

Persistent DNA damage creates a conflict between checkpoint-enforced arrest and continued proliferation. Although adaptation enables cells to escape this arrest, checkpoint bypass does not ensure renewed proliferation. Here, we show that the duration of checkpoint-associated metaphase arrest predicts proliferative re-entry after telomere dysfunction in budding yeast. Using population-level analyses and single-cell live imaging, we resolved adaptation into checkpoint attenuation, anaphase entry, mitotic completion and renewed proliferation. These transitions were separable: cells could enter anaphase yet fail to resume proliferation. Among cells that bypassed the checkpoint, each additional 100 min of metaphase arrest was associated with an 80% reduction in the odds of complete proliferative re-entry. This inverse relationship was reproducible across independent experiments and persisted across changes in spindle assembly checkpoint activity, the severity of telomere dysfunction and DNA-end metabolism, despite context-dependent shifts in arrest timing and overall proliferative competence. Comparisons across damage contexts and checkpoint states further showed that the predictive value of metaphase duration depends on the trajectory in which arrest develops. Thus, checkpoint bypass and productive proliferation are separable outcomes, with arrest duration providing a context-dependent predictor of proliferative competence after adaptation.

cell biology↗

bioRxiv2025

Safeguarding Genome Integrity: Polo-like kinase Cdc5 and phosphatase Cdc14 Orchestrate Topoisomerase II-Mediated Catenane Resolution in Mitosis

Resolution of sister chromatid intertwines in mitosis is vital for safeguarding genome integrity. While cohesin, condensin, the polo-like kinase Cdc5, and the phosphatase Cdc14 have all been implicated in this process, the underlying molecular mechanisms remain elusive. Our study unveils a coordination between spindle elongation and the timely resolution of DNA linkages, orchestrated by Cdc14 and Cdc5. We show that Cdc14 and Cdc5 collaborate to facilitate the resolution of DNA catenanes, the predominant species of DNA intertwines in mitosis, by regulating Topoisomerase II (Top2) function, both through SUMOylation and phosphorylation. Our findings contribute to unraveling a mechanism wherein Cdc5 and Cdc14 work together to ensure the timely removal of all sources of linkages between sister chromatids, thereby preserving the integrity of chromosome segregation and genome stability.

genetics↗

bioRxiv2025

A Spatial Multi-Omic Framework Identifies Gliomas Permissive to TIL Expansion

Tumor-infiltrating lymphocyte (TIL) therapy is effective in several tumor types; however, its feasibility in immune subversive tumors like glioblastoma is unclear. We expanded TILs from glioblastoma specimens and observed marked variability in yield, composition, function, and TCR clonality. By interrogating TILs expanded ex vivo alongside their sourced glioma tissue, we sought to identify determinants of successful (TIL+) vs unsuccessful TIL expansion (TIL-). Expanded TILs were predominantly effector memory CD4 cells and exhibited oligoclonal TCR enrichment. Despite similar T cell abundance in TIL vs TIL- tumors, TIL tumors exhibited distinct spatial organization and cellular interactions, including increased endothelial-immune interactions/ proximity and enrichment of vascular-associated niches. CD4 T cells localized near CD68 macrophages in TIL tumors, while they were positioned near CD163 CD206 macrophages in TIL- tumors. Thus, TIL expansion and functionality are linked to spatial organization and myeloid context; these features may enable biomarker-driven stratification for future TIL therapy in gliomas.

cancer biology↗

bioRxiv2019

3D Exploration of the Brainstem in 50-micron Resolution MRI

The brainstem, a structure of vital importance in the mammals, is currently becoming a principal focus in cognitive, affective and clinical neuroscience. Midbrain, pontine and medullar structures are the epicenter of conduit, cranial nerve and such integrative functions as consciousness, emotional processing, pain and motivation. In this study, we parcellated the nuclear masses and the principal fiber pathways that were visible in a high resolution T2-weighted MRI dataset of 50-micron isotropic voxels of a postmortem human brainstem. Based on this analysis, we generated a detailed map of the human brainstem. To assess the validity of our maps, we compared our observations with histological maps of traditional human brainstem atlases. Moreover, we reconstructed the motor, sensory and integrative neural systems of the brainstem and rendered them in 3D representations. We anticipate the utilization of these maps by the neuroimaging community at large for applications in basic neuroscience as well as in neurology, psychiatry and neurosurgery, due to their versatile computational nature in 2D and 3D representations in a publicly available capacity.

neuroscience↗

bioRxiv2019

Mapping the human subcortical auditory system using histology, post mortem MRI and in vivo MRI at 7T

Studying the human subcortical auditory system non-invasively is challenging due to its small, densely packed structures deep within the brain. Additionally, the elaborate three-dimensional (3-D) structure of the system can be difficult to understand based on currently available 2-D schematics and animal models. We addressed these issues using a combination of histological data, post mortem magnetic resonance imaging (MRI), and in vivo MRI at 7 Tesla. We created anatomical atlases based on state-of-the-art human histology (BigBrain) and post mortem MRI (50 m). We measured functional MRI (fMRI) responses to natural sounds and demonstrate that the functional localization of subcortical structures is reliable within individual participants who were scanned in two different experiments. Further, a group functional atlas derived from the functional data locates these structures with a median distance below 2mm. Using diffusion MRI tractography, we revealed structural connectivity maps of the human subcortical auditory pathway both in vivo (1050 m isotropic resolution) and post mortem (200 m isotropic resolution). This work captures current MRI capabilities for investigating the human subcortical auditory system, describes challenges that remain, and contributes novel, openly available data, atlases, and tools for researching the human auditory system.

neuroscience↗

bioRxiv2017

Mapping nonapoptotic caspase activity with a transgenic reporter in mice

The protease caspase-3 is a key mediator of apoptotic programmed cell death. But weak or transient caspase activity can contribute to neuronal differentiation, axonal pathfinding, and synaptic long-term depression. Despite the importance of sublethal, or nonapoptotic, caspase activity in neurodevelopment and neural plasticity, there has been no simple method for mapping and quantifying nonapoptotic caspase activity in rodent brains. We therefore generated a transgenic mouse expressing a highly sensitive and specific fluorescent reporter of caspase activity, with peak signal localized to the nucleus. As a proof of concept, we first obtained evidence that nonapoptotic caspase activity influences neurophysiology in an amygdalar circuit. Then focusing on the amygdala, we were able to quantify a sex-specific persistent elevation in caspase activity in females after restraint stress. This simple in vivo caspase activity reporter will facilitate systems-level studies of apoptotic and nonapoptotic phenomena in behavioral and pathological models. Significance StatementCaspase-3 is an enzyme that can cause cell death when highly active but can also perform important cellular functions, such as maturation and structural changes, when only weakly or transiently active. Despite the importance of this nonlethal type of caspase activity, there is no straightforward method to measure it in live rodents. We therefore developed mice that have a fluorescent reporter that is sensitive enough to detect nonlethal caspase activity. Surprisingly, we found that weak caspase activity influences the synchrony of neuronal firing across different brain regions. We also observed increased caspase activity in female mice after severe stress. This simple caspase activity reporter can subserve multiple applications in behavior and pathology research.

neuroscience↗