Mcmahanbradley2604

Evidence suggests encoding of recent episodic experiences may be enhanced by a subsequent salient event. We tested this hypothesis by giving rats a 3-min unsupervised experience with four odors and measuring retention after different delays. Animals recognized that a novel element had been introduced to the odor set at 24 but not 48 h. However, when odor sampling was followed within 5 min by salient light flashes or bedding odor, the memory lasted a full 2 d. These results describe a retroactive influence of salience to promote storage of episodic information and introduce a unique model for studying underlying plasticity mechanisms.The brain processes underlying impairing effects of emotional arousal on associative memory were previously attributed to two dissociable routes using high-resolution fMRI of the MTL (Madan et al. 2017). Extrahippocampal MTL regions supporting associative encoding of neutral pairs suggested unitization; conversely, associative encoding of negative pairs involved compensatory hippocampal activity. Here, whole-brain fMRI revealed prefrontal contributions dmPFC was more involved in hippocampal-dependent negative pair learning and vmPFC in extrahippocampal neutral pair learning. Successful encoding of emotional memory associations may require emotion regulation/conflict resolution (dmPFC), while neutral memory associations may be accomplished by anchoring new information to prior knowledge (vmPFC).How does the time of day of a practice session affect learning of a new motor sequence in the elderly? Participants practiced a given finger tapping sequence either during morning or evening hours. All participants robustly improved performance speed within the session concurrent with a reorganization of the tapping pattern of the sequence. However, evening-trained participants showed additional gains overnight and at 1 wk posttraining; moreover, evening training led to a further reorganization of the tapping pattern offline. A learning experience preceding nocturnal sleep can lead to a task-specific movement routine as an expression of novel "how to" knowledge in the elderly.This study describes two complementary methods that use network-based and sequence similarity tools to identify drug repurposing opportunities predicted to modulate viral proteins. This approach could be rapidly adapted to new and emerging viruses. PF-06650833 inhibitor The first method built and studied a virus-host-physical interaction network; a three-layer multimodal network of drug target proteins, human protein-protein interactions, and viral-host protein-protein interactions. The second method evaluated sequence similarity between viral proteins and other proteins, visualized by constructing a virus-host-similarity interaction network. Methods were validated on the human immunodeficiency virus, hepatitis B, hepatitis C, and human papillomavirus, then deployed on SARS-CoV-2. Comparison of virus-host-physical interaction predictions to known antiviral drugs had AUCs of 0.69, 0.59, 0.78, and 0.67, respectively, reflecting that the scores are predictive of effective drugs. For SARS-CoV-2, 569 candidate drugs were predicted, of which 37 had been included in clinical trials for SARS-CoV-2 (AUC = 0.75, P-value 3.21 × 10-3). As further validation, top-ranked candidate antiviral drugs were analyzed for binding to protein targets in silico; binding scores generated by BindScope indicated a 70% success rate.Master transcription factors control the transcriptional program and are essential to maintain cellular functions. Among them, steroid nuclear receptors, such as the estrogen receptor α (ERα), are central to the etiology of hormone-dependent cancers which are accordingly treated with corresponding endocrine therapies. However, resistance invariably arises. Here, we show that high levels of the stress response master regulator, the heat shock factor 1 (HSF1), are associated with antiestrogen resistance in breast cancer cells. Indeed, overexpression of HSF1 leads to ERα degradation, decreased expression of ERα-activated genes, and antiestrogen resistance. Furthermore, we demonstrate that reducing HSF1 levels reinstates expression of the ERα and restores response to antiestrogens. Last, our results establish a proof of concept that inhibition of HSF1, in combination with antiestrogens, is a valid strategy to tackle resistant breast cancers. Taken together, we are proposing a mechanism where high HSF1 levels interfere with the ERα-dependent transcriptional program leading to endocrine resistance in breast cancer.We establish the equivalence between the Sobolev seminorm [Formula see text] and a quantity obtained when replacing strong [Formula see text] by weak [Formula see text] in the Gagliardo seminorm [Formula see text] computed at [Formula see text] As corollaries we derive alternative estimates in some exceptional cases (involving [Formula see text]) where the "anticipated" fractional Sobolev and Gagliardo-Nirenberg inequalities fail.Secondary organic aerosol (SOA) produced by atmospheric oxidation of primary emitted precursors is a major contributor to fine particulate matter (PM2.5) air pollution worldwide. Observations during winter haze pollution episodes in urban China show that most of this SOA originates from fossil-fuel combustion but the chemical mechanisms involved are unclear. Here we report field observations in a Beijing winter haze event that reveal fast aqueous-phase conversion of fossil-fuel primary organic aerosol (POA) to SOA at high relative humidity. Analyses of aerosol mass spectra and elemental ratios indicate that ring-breaking oxidation of POA aromatic species, leading to functionalization as carbonyls and carboxylic acids, may serve as the dominant mechanism for this SOA formation. A POA origin for SOA could explain why SOA has been decreasing over the 2013-2018 period in response to POA emission controls even as emissions of volatile organic compounds (VOCs) have remained flat.Low complexity (LC) head domains 92 and 108 residues in length are, respectively, required for assembly of neurofilament light (NFL) and desmin intermediate filaments (IFs). As studied in isolation, these IF head domains interconvert between states of conformational disorder and labile, β-strand-enriched polymers. Solid-state NMR (ss-NMR) spectroscopic studies of NFL and desmin head domain polymers reveal spectral patterns consistent with structural order. A combination of intein chemistry and segmental isotope labeling allowed preparation of fully assembled NFL and desmin IFs that could also be studied by ss-NMR. Assembled IFs revealed spectra overlapping with those observed for β-strand-enriched polymers formed from the isolated NFL and desmin head domains. Phosphorylation and disease-causing mutations reciprocally alter NFL and desmin head domain self-association yet commonly impede IF assembly. These observations show how facultative structural assembly of LC domains via labile, β-strand-enriched self-interactions may broadly influence cell morphology.