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King, M.

Publications and source records attributed to King, M..

4 recordsLinked to original sources

A Multi-Domain Task Battery Reveals Functional Boundaries in the Human Cerebellum

There is compelling evidence that the human cerebellum is engaged in a wide array of motor and cognitive tasks. A fundamental question centers on whether the cerebellum is organized into distinct functional sub-regions. To address this question, we employed a rich task battery, designed to tap into a broad range of cognitive processes. During four functional magnetic resonance imaging (fMRI) sessions, participants performed a battery of 26 diverse tasks comprising 47 unique conditions. Using the data from this multi-domain task battery, we derived a comprehensive functional parcellation of the cerebellar cortex, and evaluated it by predicting functional boundaries in a novel set of tasks. The new parcellation successfully identified distinct functional sub-regions, providing significant improvements over existing parcellations derived from task-free data. Lobular boundaries, commonly used to summarize functional data, did not coincide with functional subdivisions. This multi-domain task approach offers novel insights into the functional heterogeneity of the cerebellar cortex.

neuroscience

Similarity judgments and cortical visual responses reflect different properties of object and scene categories in naturalistic images

Numerous factors have been reported to underlie the representation of complex images in high-level human visual cortex, including categories (e.g. faces, objects, scenes), animacy, and real-world size, but the extent to which this organization is reflected in behavioral judgments of real-world stimuli is unclear. Here, we compared representations derived from explicit similarity judgments and ultra-high field (7T) fMRI of human visual cortex for multiple exemplars of a diverse set of naturalistic images from 48 object and scene categories. Behavioral judgements revealed a coarse division between man-made (including humans) and natural (including animals) images, with clear groupings of conceptually-related categories (e.g. transportation, animals), while these conceptual groupings were largely absent in the fMRI representations. Instead, fMRI responses tended to reflect a separation of both human and non-human faces/bodies from all other categories. This pattern yielded a statistically significant, but surprisingly limited correlation between the two representational spaces. Further, comparison of the behavioral and fMRI representational spaces with those derived from the layers of a deep neural network (DNN) showed a strong correspondence with behavior in the top-most layer and with fMRI in the mid-level layers. These results suggest that there is no simple mapping between responses in high-level visual cortex and behavior - each domain reflects different visual properties of the images and responses in high-level visual cortex may correspond to intermediate stages of processing between basic visual features and the conceptual categories that dominate the behavioral response.\n\nSignificance StatementIt is commonly assumed there is a correspondence between behavioral judgments of complex visual stimuli and the response of high-level visual cortex. We directly compared these representations across a diverse set of naturalistic object and scene categories and found a surprisingly and strikingly different representational structure. Further, both types of representation showed good correspondence with a deep neural network, but each correlated most strongly with different layers. These results show that behavioral judgments reflect more conceptual properties and visual cortical fMRI responses capture more general visual features. Collectively, our findings highlight that great care must be taken in mapping the response of visual cortex onto behavior, which clearly reflect different information.

neuroscience

Loading of piperlongumine to liposomes after complexation with β-cyclodextrin and its effect on viability of colon and prostate cancer cells

Use of nano carriers to treat cancer is attractive due to their advantages such as the sustained release of drugs and ability to target specific regions of the body where treatment is needed. However, loading water insoluble chemotherapeutic drugs into liposomes is challenging. In this study, we developed a method to encapsulate water-insoluble drug (piperlongumine) in liposomes by complexing piperlongumine with {beta}-Cyclodextrin. Liposomes encapsulated with piperlongumine incubated with COLO 205 and PC-3 cell lines and demonstrated that viability of COLO 205 and PC-3 cells decreases to 7% and 41% respectively when the piperlongumine concentration is at 20 M.

bioengineering

Mass Action Kinetic Model of Apoptosis by TRAIL-Functionalized Leukocytes

1 AbstractO_ST_ABSBackgroundC_ST_ABSMetastasis through the bloodstream contributes to poor prognosis in many types of cancer. A unique approach to target and kill colon, prostate, and other epithelial-type cancer cells in the blood has been recently developed that causes circulating leukocytes to present the cancer-specific, liposome-bound Tumor Necrosis Factor (TNF)-related apoptosis inducing ligand (TRAIL) on their surface along with E - selectin adhesion receptors. This approach, demonstrated both in vitro with human blood and in mice, mimics the cytotoxic activity of natural killer cells. The resulting liposomal TRAIL-coated leukocytes hold promise as an effective means to neutralize circulating tumor cells that enter the bloodstream with the potential to form new metastases.\n\nResultsThe computational biology study reported here examines the mechanism of this effective signal delivery, by considering the kinetics of the coupled reaction cascade, from TRAIL binding death receptor to eventual apoptosis. In this study, a collision of bound TRAIL with circulating tumor cells (CTCs) is considered and compared to a prolonged exposure of CTCs to soluble TRAIL. An existing computational model of soluble TRAIL treatment was modified to represent the kinetics from a diffusion-limited 3D reference frame into a 2D collision frame with advection and adhesion to mimic the E - selectin and membrane bound TRAIL treatment. Thus, the current model recreates the new approach of targeting cancer cells within the blood. The model was found to faithfully reproduce representative observations from experiments of liposomal TRAIL treatment under shear. The model predicts apoptosis of CTCs within 2 hr when treated with membrane bound TRAIL, while apoptosis in CTCs treated with soluble TRAIL proceeds much more slowly over the course of 10 hrs, consistent with previous experiments. Given the clearance rate of soluble TRAIL in vivo, this model predicts that the soluble TRAIL method would be rendered ineffective, as found in previous experiments.\n\nConclusionThis study therefore indicates that the kinetics of the coupled reaction cascade of liposomal E - selectin and membrane bound TRAIL colliding with CTCs can explain why this new approach to target and kill cancer cells in blood is much more effective than its soluble counterpart.

bioengineering