A Drosophila Model for Clostridium difficile Toxin CDT Reveals Interactions with Multiple Effector Pathways.

Clostridium difficile infections (CDIs) cause severe and occasionally life-threatening diarrhea. Hyper-virulent strains produce CDT, a toxin that ADP-ribosylates actin monomers and inhibits actin polymerization. We created transgenic Drosophila lines expressing the catalytic subunit CDTa to investigate its interaction with host signaling pathways in vivo. When expressed in the midgut, CDTa reduces body weight and fecal output and compromises survival, suggesting severe impairment of digestive functions. At the cellular level, CDTa induces F-actin network collapse, elimination of the intestinal brush border, and disruption of intercellular junctions. We confirm toxin-dependent re-distribution of Rab11 to enterocytes' apical surface and observe suppression of CDTa phenotypes by a Dominant-Negative form of Rab11 or RNAi of the dedicated Rab11GEF Crag (DENND4). We also report that Calmodulin (Cam) is required to mediate CDTa activity. In parallel, chemical inhibition of the Cam/Calcineurin pathway by Cyclosporin A or FK506 also reduces CDTa phenotypes, potentially opening new avenues for treating CDIs

Lightness Dependencies and the Effect of Texture on Suprathreshold Lightness Tolerances

A psychophysical experiment was performed to determine the effects of lightness dependency on suprathreshold lightness tolerances. Using a pass/fail method of constant stimuli, lightness tolerance thresholds were measured using achromatic stimuli centered at CIELAB L* = 10, 20, 40, 60, 80, and 90 using 44 observers. In addition to measuring tolerance thresholds for uniform samples, lightness tolerances were measured using stimuli with a simulated texture of thread wound on a card. A texture intermediate between the wound thread and the uniform stimuli was also used. A computer-controlled CRT was used to perform the experiments. Lightness tolerances were found to increase with increasing lightness of the test stimuli. For the uniform stimuli this effect was only evident at the higher lightnesses. For the textured stimuli, this trend was more evident throughout the whole lightness range. Texture had an effect of increasing the tolerance thresholds by a factor of almost 2 as compared to the uniform stimuli. The intermediate texture had tolerance thresholds that were between those of the uniform and full-textured stimuli. Transforming the results into a plot of threshold vs. intensity produced results that were more uniform across the three conditions. This may indicate that CIELAB is not the best space in which to model these effects

Generating Driving Scenes with Diffusion

In this paper we describe a learned method of traffic scene generation designed to simulate the output of the perception system of a self-driving car. In our "Scene Diffusion" system, inspired by latent diffusion, we use a novel combination of diffusion and object detection to directly create realistic and physically plausible arrangements of discrete bounding boxes for agents. We show that our scene generation model is able to adapt to different regions in the US, producing scenarios that capture the intricacies of each region.Comment: Accepted to the ICRA Scalable Autonomous Driving Worksho

COMPUTING RATIONAL POWERS OF MONOMIAL IDEALS

This paper concerns fractional powers of monomial ideals. Rational powers of a monomial ideal generalize the integral closure operation as well as recover the family of symbolic powers. They also highlight many interesting connections to the theory of convex polytopes. We provide multiple algorithms for computing the rational powers of a monomial ideal. We also introduce a mild generalization allowing real powers of monomial ideals. An important result is that given any monomial ideal I, the function taking a real number to the corresponding real power of I is a step function which is left continuous and has rational discontinuity points

Pins & Needles: Towards Limb Disownership in Augmented Reality

The seemingly stable construct of our bodily self depends on the continued, successful integration of multisensory feedback about our body, rather than its purely physical composition. Accordingly, pathological disruption of such neural processing is linked to striking alterations of the bodily self, ranging from limb misidentification to disownership, and even the desire to amputate a healthy limb. While previous embodiment research has relied on experimental setups using supernumerary limbs in variants of the Rubber Hand Illusion, we here used Augmented Reality to directly manipulate the feeling of ownership for one's own, biological limb. Using a Head-Mounted Display, participants received visual feedback about their own arm, from an embodied first-person perspective. In a series of three studies, in independent cohorts, we altered embodiment by providing visuotactile feedback that could be synchronous (control condition) or asynchronous (400ms delay, Real Hand Illusion). During the illusion, participants reported a significant decrease in ownership of their own limb, along with a lowered sense of agency. Supporting the right-parietal body network, we found an increased illusion strength for the left upper limb as well as a modulation of the feeling of ownership during anodal transcranial direct current stimulation. Extending previous research, these findings demonstrate that a controlled, visuotactile conflict about one's own limb can be used to directly and systematically modulate ownership - without a proxy. This not only corroborates the malleability of body representation but questions its permanence. These findings warrant further exploration of combined VR and neuromodulation therapies for disorders of the bodily self

Scenario Diffusion: Controllable Driving Scenario Generation With Diffusion

Automated creation of synthetic traffic scenarios is a key part of validating the safety of autonomous vehicles (AVs). In this paper, we propose Scenario Diffusion, a novel diffusion-based architecture for generating traffic scenarios that enables controllable scenario generation. We combine latent diffusion, object detection and trajectory regression to generate distributions of synthetic agent poses, orientations and trajectories simultaneously. To provide additional control over the generated scenario, this distribution is conditioned on a map and sets of tokens describing the desired scenario. We show that our approach has sufficient expressive capacity to model diverse traffic patterns and generalizes to different geographical regions.Comment: NeurIPS 202

Transcriptional Responses of Different Brain Cell Types to Oxygen Decline

Brain hypoxia is associated with a wide range of physiological and clinical conditions. Although oxygen is an essential constituent of maintaining brain functions, our understanding of how specific brain cell types globally respond and adapt to decreasing oxygen conditions is incomplete. In this study, we exposed mouse primary neurons, astrocytes, and microglia to normoxia and two hypoxic conditions and obtained genome-wide transcriptional profiles of the treated cells. Analysis of differentially expressed genes under conditions of reduced oxygen revealed a canonical hypoxic response shared among different brain cell types. In addition, we observed a higher sensitivity of neurons to oxygen decline, and dissected cell type-specific biological processes affected by hypoxia. Importantly, this study establishes novel gene modules associated with brain cells responding to oxygen deprivation and reveals a state of profound stress incurred by hypoxia

Cas9/Nickase-induced allelic Conversion By Homologous Chromosome-Templated Repair in

Repair of double-strand breaks (DSBs) in somatic cells is primarily accomplished by error-prone nonhomologous end joining and less frequently by precise homology-directed repair preferentially using the sister chromatid as a template. Here,