A Simplified Crossing Fiber Model in Diffusion Weighted Imaging

Diffusion MRI (dMRI) is a vital source of imaging data for identifying anatomical connections in the living human brain that form the substrate for information transfer between brain regions. dMRI can thus play a central role toward our understanding of brain function. The quantitative modeling and analysis of dMRI data deduces the features of neural fibers at the voxel level, such as direction and density. The modeling methods that have been developed range from deterministic to probabilistic approaches. Currently, the Ball-and-Stick model serves as a widely implemented probabilistic approach in the tractography toolbox of the popular FSL software package and FreeSurfer/TRACULA software package. However, estimation of the features of neural fibers is complex under the scenario of two crossing neural fibers, which occurs in a sizeable proportion of voxels within the brain. A Bayesian non-linear regression is adopted, comprised of a mixture of multiple non-linear components. Such models can pose a difficult statistical estimation problem computationally. To make the approach of Ball-and-Stick model more feasible and accurate, we propose a simplified version of Ball-and-Stick model that reduces parameter space dimensionality. This simplified model is vastly more efficient in the terms of computation time required in estimating parameters pertaining to two crossing neural fibers through Bayesian simulation approaches. Moreover, the performance of this new model is comparable or better in terms of bias and estimation variance as compared to existing models

Enhancers activation by CRISPR/Cas9-based acetyltransferase rescues loss of function in CREBBP point mutant

https://openworks.mdanderson.org/sumexp23/1029/thumbnail.jp

Myosin IIA-mediated forces regulate multicellular integrity during vascular sprouting

Angiogenic sprouting is a critical process involved in vascular network formation within tissues. During sprouting, tip cells and ensuing stalk cells migrate collectively into the extracellular matrix while preserving cell-cell junctions, forming patent structures that support blood flow. Although several signaling pathways have been identified as controlling sprouting, it remains unclear to what extent this process is mechanoregulated. To address this question, we investigated the role of cellular contractility in sprout morphogenesis, using a biomimetic model of angiogenesis. Three-dimensional maps of mechanical deformations generated by sprouts revealed that mainly leader cells, not stalk cells, exert contractile forces on the surrounding matrix. Surprisingly, inhibiting cellular contractility with blebbistatin did not affect the extent of cellular invasion but resulted in cell-cell dissociation primarily between tip and stalk cells. Closer examination of cell-cell junctions revealed that blebbistatin impaired adherens-junction organization, particularly between tip and stalk cells. Using CRISPR/Cas9-mediated gene editing, we further identified NMIIA as the major isoform responsible for regulating multicellularity and cell contractility during sprouting. Together, these studies reveal a critical role for NMIIA-mediated contractile forces in maintaining multicellularity during sprouting and highlight the central role of forces in regulating cell-cell adhesions during collective motility.R01 EB000262 - NIBIB NIH HHS; R01 HL115553 - NHLBI NIH HHSPublished versio

Evaluation of the TruNarc Handheld Narcotics Analyzer as a Pre-Analysis Screening Device for the Orange County Crime Lab

Forensic analysis of suspected narcotics is often dangerous as the substances’ composition is unknown. Many techniques for drug identification require handling of the substance outside of its packaging, which can expose the analyst to potentially harmful chemicals. The TruNarc Handheld Narcotics Analyzer is a portable Raman spectroscopy device that is non-destructive of evidence and can be used to screen drugs through simple packaging to minimize the risk of exposure. The Orange County Crime Lab (OCCL) is testing the limits of this device to determine if it can be used to screen new evidence within the Seized Drugs Lab. The OCCL has used this device on over 85 pieces of individual casework, which were then confirmed using gas chromatography and mass spectrometry (GC/MS). Methamphetamine, cocaine, and fentanyl in various forms such as powders, crystalline substances, and tablets, are all drugs we are optimistic that the TruNarc will be able to accurately identify in casework. We found that the three drugs of interest could be identified in most cases where substances were light in color, in powder or crystalline form, and in translucent plastic packaging. However, mixtures and tablets were difficult for the TruNarc to accurately identify. Further testing will be done to determine the lower limits of detection for drugs of interest before making a decision on implementing the device as a pre-analysis screening method in the laboratory and field settings

Imaging striatal dopamine release using a nongenetically encoded near infrared fluorescent catecholamine nanosensor.

Neuromodulation plays a critical role in brain function in both health and disease, and new tools that capture neuromodulation with high spatial and temporal resolution are needed. Here, we introduce a synthetic catecholamine nanosensor with fluorescent emission in the near infrared range (1000-1300 nm), near infrared catecholamine nanosensor (nIRCat). We demonstrate that nIRCats can be used to measure electrically and optogenetically evoked dopamine release in brain tissue, revealing hotspots with a median size of 2 µm. We also demonstrated that nIRCats are compatible with dopamine pharmacology and show D2 autoreceptor modulation of evoked dopamine release, which varied as a function of initial release magnitude at different hotspots. Together, our data demonstrate that nIRCats and other nanosensors of this class can serve as versatile synthetic optical tools to monitor neuromodulatory neurotransmitter release with high spatial resolution

Low Arousal Positive Emotional Stimuli Attenuate Aberrant Working Memory Processing in Persons with Mild Cognitive Impairment

Emotional enhancement effects on memory have been reported to mitigate the pathophysiology of Alzheimer’s disease (AD). However, relative to their manifestation in persons without pathologic aging, these effects may be reduced in magnitude or even deleterious, especially in tasks that more closely model ecologic memory performance. Based upon a synthesis of such reports, we hypothesized that in persons with AD low arousal positive stimuli would evoke relatively intact emotional enhancement effects, but that high arousal negative stimuli would evoke disordered emotional enhancement effects. To assess this, participants with and without mild cognitive impairment (MCI) presumed to be due to AD performed an emotionally-valenced short-term memory task while encephalography was recorded. Results indicated that for persons with MCI, high arousal negative stimuli led to working memory processing patterns previously associated with MCI presumed due to AD and dementia of the Alzheimer-type. In contrast, low arousal positive stimuli evoked a processing pattern similar to MCI participants’ unaffected spouses. Our current findings suggest that low arousal positive stimuli attenuate working memory deficits of MCI due to AD

Structure-based inhibitors of amyloid beta core suggest a common interface with tau.

Alzheimer's disease (AD) pathology is characterized by plaques of amyloid beta (Aβ) and neurofibrillary tangles of tau. Aβ aggregation is thought to occur at early stages of the disease, and ultimately gives way to the formation of tau tangles which track with cognitive decline in humans. Here, we report the crystal structure of an Aβ core segment determined by MicroED and in it, note characteristics of both fibrillar and oligomeric structure. Using this structure, we designed peptide-based inhibitors that reduce Aβ aggregation and toxicity of already-aggregated species. Unexpectedly, we also found that these inhibitors reduce the efficiency of Aβ-mediated tau aggregation, and moreover reduce aggregation and self-seeding of tau fibrils. The ability of these inhibitors to interfere with both Aβ and tau seeds suggests these fibrils share a common epitope, and supports the hypothesis that cross-seeding is one mechanism by which amyloid is linked to tau aggregation and could promote cognitive decline

“No powers, man!”: A student perspective on designing university smart building interactions

Smart buildings offer an opportunity for better performance and enhanced experience by contextualising services and interactions to the needs and practices of occupants. Yet, this vision is limited by established approaches to building management, delivered top-down through professional facilities management teams, opening up an interaction-gap between occupants and the spaces they inhabit. To address the challenge of how smart buildings might be more inclusively managed, we present the results of a qualitative study with student occupants of a smart building, with design workshops including building walks and speculative futuring. We develop new understandings of how student occupants conceptualise and evaluate spaces as they experience them, and of how building management practices might evolve with new sociotechnical systems that better leverage occupant agency. Our findings point to important directions for HCI research in this nascent area, including the need for HBI (Human-Building Interaction) design to challenge entrenched roles in building management