A numerically efficient implementation of the expectation maximization algorithm for state space models

Peer reviewedPostprin

Early-life adversity selectively impairs α2-GABAA receptor expression in the mouse nucleus accumbens and influences the behavioral effects of cocaine

Haplotypes of the Gabra2 gene encoding the α2 subunit of the GABAA receptor (GABAAR) are associated with drug abuse, suggesting that α2-GABAARs may play an important role in the circuitry underlying drug misuse. The genetic association of Gabra2 haplotypes with cocaine addiction appears to be evident primarily in individuals who had experienced childhood trauma. Given this association of childhood trauma, cocaine abuse and the Gabra2 haplotypes, we have explored in a mouse model of early life adversity (ELA) whether such events influence the behavioral effects of cocaine and if, as suggested by the human studies, α2-GABAARs in the nucleus accumbens (NAc) are involved in these perturbed behaviors. In adult mice prior ELA caused a selective decrease of accumbal α2-subunit mRNA, resulting in a selective decrease in the number and size of the α2-subunit (but not the α1-subunit) immunoreactive clusters in NAc core medium spiny neurons (MSNs). Functionally, in adult MSNs ELA decreased the amplitude and frequency of GABAAR-mediated miniature inhibitory postsynaptic currents (mIPSCs), a profile similar to that of α2 "knock-out" (α2-/-) mice. Behaviorally, adult male ELA and α2-/- mice exhibited an enhanced locomotor response to acute cocaine and blunted sensitization upon repeated cocaine administration, when compared to their appropriate controls. Collectively, these findings reveal a neurobiological mechanism which may relate to the clinical observation that early trauma increases the risk for substance abuse disorder (SAD) in individuals harbouring haplotypic variations in the Gabra2 gene.</p

Genome Sequencing of SHH Medulloblastoma Predicts Genotype-Related Response to Smoothened Inhibition

SummarySmoothened (SMO) inhibitors recently entered clinical trials for sonic-hedgehog-driven medulloblastoma (SHH-MB). Clinical response is highly variable. To understand the mechanism(s) of primary resistance and identify pathways cooperating with aberrant SHH signaling, we sequenced and profiled a large cohort of SHH-MBs (n = 133). SHH pathway mutations involved PTCH1 (across all age groups), SUFU (infants, including germline), and SMO (adults). Children >3 years old harbored an excess of downstream MYCN and GLI2 amplifications and frequent TP53 mutations, often in the germline, all of which were rare in infants and adults. Functional assays in different SHH-MB xenograft models demonstrated that SHH-MBs harboring a PTCH1 mutation were responsive to SMO inhibition, whereas tumors harboring an SUFU mutation or MYCN amplification were primarily resistant

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Are the directions of both eyes integrated before or after the perception of direct gaze? Evidence from simulated mild strabismus

Horstmann G, Linke L. Are the directions of both eyes integrated before or after the perception of direct gaze? Evidence from simulated mild strabismus. Perception. 2023.The cone of gaze is a looker's range of gaze directions that is accepted as direct by an observer. The present research asks how the condition of mild strabismus, that is, when the two eyes point in slightly different directions, influences the cone of gaze. Normally, both eyes are rotated in a coordinated manner such that both eyes are directed to the same fixation point. With strabismus, there are two fixation points, and, therefore, two directions into which the two eyes point. This raises the question of the direction and the shape (i.e., width) of the gaze cone. Two experiments are conducted with simulated mild strabismus. Three conditions are tested, the two strabismic conditions of esotropia, and exotropia and one orthotropic (nonstrabismic) condition. Results show that the direction of the gaze cone is roughly the average of the directions of the two eyes. Furthermore, the width of the gaze cone is not affected by simulated strabismus and is thus the same for the strabismic and the orthotropic conditions. The results imply a model where at first the direction of gaze based on both eyes is perceived, and where the gaze cone is implied on the basis of the combined gaze direction

Perception of direct gaze in a video-conference setting: the effects of position and size

Horstmann G, Linke L. Perception of direct gaze in a video-conference setting: the effects of position and size. Cognitive Research: Principles and Implications. 2022;7: 67.A common problem in video conferences is gaze direction. In face-to-face communication, it is common that speaker and listener intermittently look at each other. In a video-conference setting, where multiple participants are on the screen, things are complicated and not necessarily optimal. If the listener feels looked at when the speaker looks into the camera, how tolerant is the listener for slight deviations? And does this depend on the position of the speaker’s tile on the screen, or the size of the tile? In a first experiment, participants from a student population judged whether they are looked at, while vertical gaze direction of the looker was varied. Furthermore, the position of the tile on the screen varied. The results showed that a slightly upward directed gaze was optimal for the direct gaze judgment, with a width of ± 4 degrees. Optimal gaze direction was somewhat higher for tiles at the bottom of the screen. A second experiment tested the effect of size on the perception of horizontal gaze directions. Size was found to increase the gaze cone. The paper concludes with some recommendations for a setup of video conference systems, optimized for perceived gaze contact

Examining Gaze Cone Shape and Size

Horstmann G, Linke L. Examining Gaze Cone Shape and Size. Perception. 2021;50(12):1056-1065.Another person's looking behavior is used by observers to judge gaze direction and fixation points. An important task in this context is the judgement of direct gaze, that is, the perception of being looked at. The cone of gaze can be defined as the range of fixation points that support direct gaze. The cone concept implies that this range lawfully increases with distance, but that the cone angle is constant. The present experiment tested the concept with a larger number and a more extended range of distances than previously done, and took care of possible directional errors. The gaze cone was found to be roughly linear, and stable between 1.6 m and 7.9 m – an almost perfect cone. The mean cone size subtended 5.2° in diameter when averaged over ascending and descending series. Measures differed, however, in ascending and descending series, consistent with a conservative bias. Also, the variability of judgements increased slightly with distance. Results are discussed considering whether cone size is actually smaller than often reported in the literature

How vergence influences the perception of being looked at

Linke L, Horstmann G. How vergence influences the perception of being looked at. Perception. 2022: 030100662211223.Perceiving other people's direct gaze is important for many areas of everyday activity. For horizontal and vertical eye movements, the area of being looked at, known as the cone of gaze, has been well explored. Previous research has shown a range of eye rotations (up to eccentricities of 4°–9°) that people accept as direct gaze. Vergence is an important cue for perceiving the depth of fixation. This study examines the range of vergence angles that support the perception of being looked at. In two experiments, observers adjusted the degree of vergence of the lookers’ eyes until they felt just (not) looked at. The first experiment also asked to adjust the point of being exactly looked at, which was 0° (parallel eyes). The thresholds of being just (not) looked at were around 4.5° of convergence and 2.5° divergence, which results in a depth of 7° of vergence. This depth was replicated in Experiment 2, while the thresholds of convergence (3.5°) and divergence (3.5°) slightly differ from Experiment 1. The results indicate a consistent area of vergences being accepted as direct gaze, yielding first-time evidence for a third dimension—the depth dimension—of direct gaze