Bio:

Abstract: Large nuclear deformations during migration through confined spaces have been associated with nuclear membrane rupture and DNA damage. However, the stresses associated with nuclear damage remain unclear. Here, using a quasi-static plane strain finite element model, we map evolution of nuclear shape and stresses during confined migration of a cell through a deformable matrix. Plastic deformation of the nucleus observed for a cell with stiff nucleus transiting through a stiffer matrix lowered nuclear stresses, but also led to kinking of the nuclear membrane. In line with model predictions, transwell migration experiments with fibrosarcoma cells showed that while nuclear softening increased invasiveness, nuclear stiffening led to plastic deformation and higher levels of DNA damage. In addition to highlighting the advantage of nuclear softening during confined migration, our results suggest that plastic deformations of the nucleus during transit through stiff tissues may lead to bending-induced nuclear membrane disruption and subsequent DNA damage.

Abstract: A physician palpates a tissue to detect an embedded tumor nodule by sensing an increase in local tissue stiffness and nodule size. The Hertz contact model however, is unable to predict the material or physical properties of a tumor nodule embedded in a healthy tissue of finite thickness. In this study, utilizing a hyperelastic material model, we propose a general methodology to analyze the extent to which the stiffness, size and depth of a nodule embedded in a tissue affect its detectability. Using dimensional analysis, we generate simple power-law relations to predict physical and material properties of tumor nodules embedded in healthy tissue during indentation. Our results indicate that indenter radius and indentation depth are critical parameters in nodule detection and a thin indenter and large indentation depth increase detection sensitivity of an embedded tumor nodule. Our results also show that anisotropic material properties of either a tissue or an embedded nodule render the embedded tumor nodule undetectable using indentation. We define palpation sensitivity maps that can be used to predict material and physical properties of tumor nodules in healthy tissues. The analysis and results presented in this study might increase accuracy and precision in instrumented probe-based laparoscopic or robotic surgeries.

Abstract: Speech perception requires the binding of spatiotemporally disjoint auditory–visual cues. The corresponding brain network-level information processing can be characterized by two complementary mechanisms: functional segregation which refers to the localization of processing in either isolated or distributed modules across the brain, and integration which pertains to cooperation among relevant functional modules. Here, we demonstrate using functional magnetic resonance imaging recordings that subjective perceptual experience of multisensory speech stimuli, real and illusory, are represented in differential states of segregation–integration. We controlled the inter-subject variability of illusory/cross-modal perception parametrically, by introducing temporal lags in the incongruent auditory–visual articulations of speech sounds within the McGurk paradigm. The states of segregation–integration balance were captured using two alternative computational approaches. First, the module responsible for cross-modal binding of sensory signals defined as the perceptual binding network (PBN) was identified using standardized parametric statistical approaches and their temporal correlations with all other brain areas were computed. With increasing illusory perception, the majority of the nodes of PBN showed decreased cooperation with the rest of the brain, reflecting states of high segregation but reduced global integration. Second, using graph theoretic measures, the altered patterns of segregation–integration were cross-validated.