Biology subjects

Moran, R.

Publications and source records attributed to Moran, R..

3 recordsLinked to original sources

bioRxiv2018

Human noise blindness drives suboptimal cognitive inference

Humans typically make near-optimal sensorimotor judgments but show systematic biases when making more cognitive judgments. Here we test the hypothesis that, while humans are sensitive to the noise present during early sensory processing, the \"optimality gap\" arises because they are blind to noise introduced by later cognitive integration of variable or discordant pieces of information. In six psychophysical experiments, human observers judged the average orientation of an array of contrast gratings. We varied the stimulus contrast (encoding noise) and orientation variability (integration noise) of the array. Participants adapted near-optimally to changes in encoding noise, but, under increased integration noise, displayed a range of suboptimal behaviours: they ignored stimulus base rates, reported excessive confidence in their choices, and refrained from opting out of objectively difficult trials. These overconfident behaviours were captured by a Bayesian model which is blind to integration noise. Our study provides a computationally grounded explanation of suboptimal cognitive inferences.

neuroscience↗

bioRxiv2017

Propofol-Induced Unresponsiveness is Associated with Impaired Feedforward Connectivity in the Cortical Hierarchy

BackgroundImpaired consciousness has been associated with impaired cortical signal propagation following transcranial magnetic stimulation (TMS). Herein we hypothesized that the reduced current propagation under propofol-induced unresponsiveness is associated with changes in both feedforward and feedback connectivity across the cortical hierarchy.\n\nMethodsEight subjects underwent left occipital TMS coupled with high-density electroencephalograph (EEG) recordings during wakefulness and propofol-induced unconsciousness. Spectral analysis was applied to responses recorded from sensors overlying six hierarchical cortical sources involved in visual processing. Dynamic causal modelling (DCM) of evoked and induced source-space responses was used to investigate propofols effects on connectivity between regions.\n\nResultsPropofol produced a wideband reduction in evoked power following TMS in five out of six electrodes. Bayesian Model Selection supported a DCM with hierarchical feedforward and feedback connections to best fit the data. DCM of induced responses revealed that the primary effect of propofol was impaired feedforward responses in cross frequency theta/alpha-gamma coupling and within frequency theta coupling (F contrast, Family Wise Error corrected p<0.05). An exploratory analysis (thresholded at uncorrected p<0.001) also suggested that propofol impaired feedforward and feedback beta band coupling. Posthoc analyses showed impairments in all feedforward connections and one feedback connection from parietal to occipital cortex. DCM of the evoked response potential showed impaired feedforward connectivity between left sided occipital and parietal cortex (T contrast p=0.004, Bonferroni corrected).\n\nConclusionsOur data suggest that propofol-induced loss of consciousness is associated with reduced evoked power and impaired hierarchical feedforward connectivity following occipital TMS.

neuroscience↗

bioRxiv2017

The microprotein Minion controls cell fusion and muscle formation

Although recent evidence has pointed to the existence of small open reading frame (smORF)-encoded microproteins in mammals, the functional repertoire of this microproteome remains to be determined1. In skeletal muscle, proper development requires fusion of mononuclear progenitors to form multinucleated myotubes, a critical but poorly understood process2,3. Here we report the identification of a small ORF encoding an essential skeletal muscle specific microprotein we term Minion (microprotein inducer of fusion). Myogenic progenitors lacking Minion differentiate normally but fail to form syncytial myotubes, and Minion-deficient mice die perinatally with marked reduction in fused muscle fibers. This fusogenic activity is conserved to the human Minion ortholog, previously annotated as a long noncoding RNA. Loss-of-function studies demonstrate that Minion is the factor providing muscle specific fusogenic function for the transmembrane protein Myomaker4. Remarkably, we demonstrate that co-expression of Minion and Myomaker is sufficient to induce rapid cytoskeletal rearrangement and homogeneous cellular fusion, even in non-muscle cells. These findings establish Minion as a novel microprotein required for muscle development, and define a two-component program for the induction of mammalian cell fusion, enabling both research and translational applications. Importantly, these data also significantly expand the known functions of smORF-encoded microproteins, an under-explored source of proteomic diversity.

cell biology↗