Impaired recognition and regulation of disgust is associated with distinct but partially overlapping patterns of decreased gray matter volume in the ventroanterior insula

Background The ventroanterior insula is implicated in the experience, expression, and recognition of disgust; however, whether this brain region is required for recognizing disgust or regulating disgusting behaviors remains unknown. Methods We examined the brain correlates of the presence of disgusting behavior and impaired recognition of disgust using voxel-based morphometry in a sample of 305 patients with heterogeneous patterns of neurodegeneration. Permutation-based analyses were used to determine regions of decreased gray matter volume at a significance level p <=.05 corrected for family-wise error across the whole brain and within the insula. Results Patients with behavioral variant frontotemporal dementia and semantic variant primary progressive aphasia were most likely to exhibit disgusting behaviors and were, on average, the most impaired at recognizing disgust in others. Imaging analysis revealed that patients who exhibited disgusting behaviors had significantly less gray matter volume bilaterally in the ventral anterior insula. A region of interest analysis restricted to behavioral variant frontotemporal dementia and semantic variant primary progressive aphasia patients alone confirmed this result. Moreover, impaired recognition of disgust was associated with decreased gray matter volume in the bilateral ventroanterior and ventral middle regions of the insula. There was an area of overlap in the bilateral anterior insula where decreased gray matter volume was associated with both the presence of disgusting behavior and impairments in recognizing disgust. Conclusions These findings suggest that regulating disgusting behaviors and recognizing disgust in others involve two partially overlapping neural systems within the insula. Moreover, the ventral anterior insula is required for both processes

A novel rapamycin analog is highly selective for mTORC1 in vivo.

Rapamycin, an inhibitor of mechanistic Target Of Rapamycin Complex 1 (mTORC1), extends lifespan and shows strong potential for the treatment of age-related diseases. However, rapamycin exerts metabolic and immunological side effects mediated by off-target inhibition of a second mTOR-containing complex, mTOR complex 2. Here, we report the identification of DL001, a FKBP12-dependent rapamycin analog 40x more selective for mTORC1 than rapamycin. DL001 inhibits mTORC1 in cell culture lines and in vivo in C57BL/6J mice, in which DL001 inhibits mTORC1 signaling without impairing glucose homeostasis and with substantially reduced or no side effects on lipid metabolism and the immune system. In cells, DL001 efficiently represses elevated mTORC1 activity and restores normal gene expression to cells lacking a functional tuberous sclerosis complex. Our results demonstrate that highly selective pharmacological inhibition of mTORC1 can be achieved in vivo, and that selective inhibition of mTORC1 significantly reduces the side effects associated with conventional rapalogs

Uncertainty and Surprise Jointly Predict Musical Pleasure and Amygdala, Hippocampus, and Auditory Cortex Activity

Listening to music often evokes intense emotions [1, 2]. Recent research suggests that musical pleasure comes from positive reward prediction errors, which arise when what is heard proves to be better than expected [3]. Central to this view is the engagement of the nucleus accumbens—a brain region that processes reward expectations—to pleasurable music and surprising musical events [4, 5, 6, 7, 8]. However, expectancy violations along multiple musical dimensions (e.g., harmony and melody) have failed to implicate the nucleus accumbens [9, 10, 11], and it is unknown how music reward value is assigned [12]. Whether changes in musical expectancy elicit pleasure has thus remained elusive [11]. Here, we demonstrate that pleasure varies nonlinearly as a function of the listener’s uncertainty when anticipating a musical event, and the surprise it evokes when it deviates from expectations. Taking Western tonal harmony as a model of musical syntax, we used a machine-learning model [13] to mathematically quantify the uncertainty and surprise of 80,000 chords in US Billboard pop songs. Behaviorally, we found that chords elicited high pleasure ratings when they deviated substantially from what the listener had expected (low uncertainty, high surprise) or, conversely, when they conformed to expectations in an uninformative context (high uncertainty, low surprise). Neurally, we found using fMRI that activity in the amygdala, hippocampus, and auditory cortex reflected this interaction, while the nucleus accumbens only reflected uncertainty. These findings challenge current neurocognitive models of music-evoked pleasure and highlight the synergistic interplay between prospective and retrospective states of expectation in the musical experience

Epigenetic and Genetic Factors Predict Women's Salivary Cortisol following a Threat to the Social Self

10.1371/journal.pone.0048597PLoS ONE711

Transcriptome dynamics of a broad host-range cyanophage and its hosts

Cyanobacteria are highly abundant in the oceans and are constantly exposed to lytic viruses. The T4-like cyanomyoviruses are abundant in the marine environment and have broad host-ranges relative to other cyanophages. It is currently unknown whether broad host-range phages specifically tailor their infection program for each host, or employ the same program irrespective of the host infected. Also unknown is how different hosts respond to infection by the same phage. Here we used microarray and RNA-seq analyses to investigate the interaction between the Syn9 T4-like cyanophage and three phylogenetically, ecologically and genomically distinct marine Synechococcus strains: WH7803, WH8102 and WH8109. Strikingly, Syn9 led a nearly identical infection and transcriptional program in all three hosts. Different to previous assumptions for T4-like cyanophages, three temporally regulated gene expression classes were observed. Furthermore, a novel regulatory element controlled early-gene transcription, and host-like promoters drove middle gene transcription, different to the regulatory paradigm for T4. Similar results were found for the P-TIM40 phage during infection of Prochlorococcus NATL2A. Moreover, genomic and metagenomic analyses indicate that these regulatory elements are abundant and conserved among T4-like cyanophages. In contrast to the near-identical transcriptional program employed by Syn9, host responses to infection involved host-specific genes primarily located in hypervariable genomic islands, substantiating islands as a major axis of phage-cyanobacteria interactions. Our findings suggest that the ability of broad host-range phages to infect multiple hosts is more likely dependent on the effectiveness of host defense strategies than on differential tailoring of the infection process by the phage