Sensing Phosphatidylserine in Cellular Membranes

Phosphatidylserine, a phospholipid with a negatively charged head-group, is an important constituent of eukaryotic cellular membranes. On the plasma membrane, rather than being evenly distributed, phosphatidylserine is found preferentially in the inner leaflet. Disruption of this asymmetry, leading to the appearance of phosphatidylserine on the surface of the cell, is known to play a central role in both apoptosis and blood clotting. Despite its importance, comparatively little is known about phosphatidylserine in cells: its precise subcellular localization, transmembrane topology and intracellular dynamics are poorly characterized. The recent development of new, genetically-encoded probes able to detect phosphatidylserine within live cells, however, is leading to a more in-depth understanding of the biology of this phospholipid. This review aims to give an overview of the current methods for phosphatidylserine detection within cells, and some of the recent realizations derived from their use

Optimal Dark Hole Generation via Two Deformable Mirrors with Stroke Minimization

The past decade has seen a significant growth in research targeted at space based observatories for imaging exo-solar planets. The challenge is in designing an imaging system for high-contrast. Even with a perfect coronagraph that modifies the point spread function to achieve high-contrast, wavefront sensing and control is needed to correct the errors in the optics and generate a "dark hole". The high-contrast imaging laboratory at Princeton University is equipped with two Boston Micromachines Kilo-DMs. We review here an algorithm designed to achieve high-contrast on both sides of the image plane while minimizing the stroke necessary from each deformable mirror (DM). This algorithm uses the first DM to correct for amplitude aberrations and the second DM to create a flat wavefront in the pupil plane. We then show the first results obtained at Princeton with this correction algorithm, and we demonstrate a symmetric dark hole in monochromatic light

Evaluating the accuracy of diffusion MRI models in white matter

Models of diffusion MRI within a voxel are useful for making inferences about the properties of the tissue and inferring fiber orientation distribution used by tractography algorithms. A useful model must fit the data accurately. However, evaluations of model-accuracy of some of the models that are commonly used in analyzing human white matter have not been published before. Here, we evaluate model-accuracy of the two main classes of diffusion MRI models. The diffusion tensor model (DTM) summarizes diffusion as a 3-dimensional Gaussian distribution. Sparse fascicle models (SFM) summarize the signal as a linear sum of signals originating from a collection of fascicles oriented in different directions. We use cross-validation to assess model-accuracy at different gradient amplitudes (b-values) throughout the white matter. Specifically, we fit each model to all the white matter voxels in one data set and then use the model to predict a second, independent data set. This is the first evaluation of model-accuracy of these models. In most of the white matter the DTM predicts the data more accurately than test-retest reliability; SFM model-accuracy is higher than test-retest reliability and also higher than the DTM, particularly for measurements with (a) a b-value above 1000 in locations containing fiber crossings, and (b) in the regions of the brain surrounding the optic radiations. The SFM also has better parameter-validity: it more accurately estimates the fiber orientation distribution function (fODF) in each voxel, which is useful for fiber tracking

When Reasons Run Out

Subjectivists about practical normativity hold that an agent’s favoring and disfavoring attitudes give rise to practical reasons. On this view, an agent’s normative reason to choose vanilla over chocolate ice cream ultimately turns on facts about what appeals to her rather than facts about what her options are like attitude-independently. Objectivists—who ground reasons in the attitude-independent features of the things we aim at—owe us an explanation of why it is rational to choose what we favor, if not simply because favoring is a source of reasons. My aim in this paper is to supply such a story. The proposal is roughly that when an agent cannot base her choices on her judgments about what she has most reason to do, structural rationality extends to her a license to choose something just because she favors it, without imbuing favoring with the authority of a normative reason

Designing a User-Metaverse Interface for the Industrial-Metaverse

The Industrial-Metaverse will create interactions between the physical and virtual worlds to extend operations in the physical industry. This particularity and the demand for increasing immersion in the Metaverse require using XR technologies called User-Metaverse interfaces (UMI). How such a UMI must be designed for the industrial-Metaverse is unknown. This study adopts a design science approach to design a UMI based on social cognitive theory (SCT). According to SCT, creating user-generated Metaverse content is crucial to the UMI design. It empowers users to generate content through their efforts, leading to higher self-efficacy and user engagement. We formulate two theoretically based design principles and instantiate a software artifact, which we evaluate in a laboratory experiment with 57 participants. Our study shows the importance of belief in success in the design of future UMI. Furthermore, our design principles show significant positive outcome expectations of users in their interaction with the software artifact

Visual subcircuit-specific dysfunction and input-specific mispatterning in the superior colliculus of fragile X mice

Abstract Background Sensory processing deficits are frequently co-morbid with neurodevelopmental disorders. For example, patients with fragile X syndrome (FXS), caused by a silencing of the FMR1 gene, exhibit impairments in visual function specific to the dorsal system, which processes motion information. However, the developmental and circuit mechanisms underlying this deficit remain unclear. Recently, the superior colliculus (SC), a midbrain structure regulating head and eye movements, has emerged as a model for dissecting visual circuit development and function. Previous studies have demonstrated a critical role for activity-dependent processes in the development of visual circuitry in the SC. Based on the known role of the FMR1 gene product in activity-dependent synaptic plasticity, we explored the function and organization of visual circuits in the SC of a mouse model of FXS (Fmr1−/y). Methods We utilized in vivo extracellular electrophysiology in combination with computer-controlled visual stimuli to determine the receptive field properties of visual neurons in the SC of control and Fmr1−/y mice. In addition, we utilized anatomical tracing methods to assess the organization of visual inputs to the SC and along the retinogeniculocortical pathway. Results Receptive fields of visual neurons in the SC of Fmr1−/y mice were significantly larger than those found in control animals, though their shape and structure were unaffected. Further, selectivity for direction of movement was decreased, while selectivity to axis of movement was unchanged. Interestingly, axis-selective (AS) neurons exhibited a specific hyperexcitability in comparison to AS neurons in control SC and to direction-selective (DS) neurons in both control and Fmr1−/y SC. Anatomical tracings revealed that retinocollicular, retinogeniculate, and geniculocortical projections were normally organized in the absence of Fmr1. However, projections from primary visual cortex (V1) to the SC were poorly refined. Conclusions Fmr1 is required for the proper development of visual circuit organization and function in the SC. We find that visual dysfunction is heterogeneously manifested in a subcircuit-specific manner in Fmr1−/y mice, consistent with previous studies in human FXS patients. Further, we show a specific alteration of inputs to the SC from V1, but not the retina. Together, these data suggest that Fmr1 may function in distinct ways during the development of different visual subcircuits.https://deepblue.lib.umich.edu/bitstream/2027.42/144523/1/11689_2018_Article_9241.pd

Widespread duplications in the genomes of laboratory stocks of Dictyostelium discoideum.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Duplications of stretches of the genome are an important source of individual genetic variation, but their unrecognized presence in laboratory organisms would be a confounding variable for genetic analysis. RESULTS: We report here that duplications of 15 kb or more are common in the genome of the social amoeba Dictyostelium discoideum. Most stocks of the axenic 'workhorse' strains Ax2 and Ax3/4 obtained from different laboratories can be expected to carry different duplications. The auxotrophic strains DH1 and JH10 also bear previously unreported duplications. Strain Ax3/4 is known to carry a large duplication on chromosome 2 and this structure shows evidence of continuing instability; we find a further variable duplication on chromosome 5. These duplications are lacking in Ax2, which has instead a small duplication on chromosome 1. Stocks of the type isolate NC4 are similarly variable, though we have identified some approximating the assumed ancestral genotype. More recent wild-type isolates are almost without large duplications, but we can identify small deletions or regions of high divergence, possibly reflecting responses to local selective pressures. Duplications are scattered through most of the genome, and can be stable enough to reconstruct genealogies spanning decades of the history of the NC4 lineage. The expression level of many duplicated genes is increased with dosage, but for others it appears that some form of dosage compensation occurs. CONCLUSION: The genetic variation described here must underlie some of the phenotypic variation observed between strains from different laboratories. We suggest courses of action to alleviate the problem.Published versio