Neural Architecture of Hunger-Dependent Multisensory Decision Making in C. elegans

Little is known about how animals integrate multiple sensory inputs in natural environments to balance avoidance of danger with approach to things of value. Furthermore, the mechanistic link between internal physiological state and threat-reward decision making remains poorly understood. Here we confronted C. elegans worms with the decision whether to cross a hyperosmotic barrier presenting the threat of desiccation to reach a source of food odor. We identified a specific interneuron that controls this decision via top-down extrasynaptic aminergic potentiation of the primary osmosensory neurons to increase their sensitivity to the barrier. We also establish that food deprivation increases the worm's willingness to cross the dangerous barrier by suppressing this pathway. These studies reveal a potentially general neural circuit architecture for internal state control of threat-reward decision making

Lupus nephritis in Chinese children--a territory-wide cohort study in Hong Kong

We report a multicenter study of Chinese children in Hong Kong with systemic lupus erythematosus (SLE) nephritis. Children were included if: they fulfilled the ACR criteria, had significant proteinuria or casturia, were Chinese and younger than 19 years and had been diagnosed with SLE between January 1990 and December 2003. Investigators in each center retrieved data on clinical features, biopsy reports, treatment and outcome of these patients. There were 128 patients (eight boys, 120 girls; mean age: 11.9+/-2.8 years). About 50% presented with multisystem illness and 40% with nephritic/nephrotic symptoms. Negative anti-dsDNA antibodies were found in 6% of the patients. Renal biopsy revealed WHO Class II, III, IV and V nephritis in 13 (10%), 22 (17%), 69 (54%) and 13 (10%) patients, respectively. The clinical severity of the nephritis did not accurately predict renal biopsy findings. The follow-up period ranged from 1 to 16.5 years (mean+/-SD: 5.76+/-3.61 years). During the study five patients died (two from lupus flare, one from cardiomyopathy, two from infections). Four patients had endstage renal failure (ESRF) (one died during a lupus flare). All deaths and end-stage renal failure occurred in the Class IV nephritis group. Chronic organ damage was infrequent in the survivors. The actuarial patient survival rates at 5, 10 and 15 years of age were 95.3, 91.8, and 91.8%, respectively. For Class IV nephritis patients, the survival rates without ESRF at 5, 10, and 15 years were 91.5, 82.3 and 76%, respectively. The survival and chronic morbidity rates of the Chinese SLE children in the present study are comparable to those of other published studies.postprin

Dosimetry tools and techniques for IMRT

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98734/1/MPH001313.pd

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

A neural signature of choice under sensory conflict in<i>Drosophila</i>

SummaryFeeding decisions are fundamental to survival, and decision making is often disrupted in disease, yet the neuronal and molecular mechanisms of adaptive decision making are not well understood. Here we show that neural activity in a small population of neurons projecting to the fan-shaped body higher-order central brain region ofDrosophilarepresents final food choice during sensory conflict. We found that hungry flies made tradeoffs between appetitive and aversive values of food in a decision making task to choose bittersweet food with high sucrose concentration, but adulterated with bitter quinine, over sweet-only food with less sucrose. Using cell-specific optogenetics and receptor RNAi knockdown during the decision task, we identified an upstream neuropeptidergic and dopaminergic network that relays internal state and other decision-relevant information, such as valence and previous experience, to a specific subset of fan-shaped body neurons. Importantly, calcium imaging revealed that these neurons were strongly inhibited by the taste of the rejected food choice, suggesting that they encode final behavioral food choice. Our findings reveal that fan-shaped body taste responses to food choices are determined not only by taste quality, but also by previous experience (including choice outcome) and hunger state, which are integrated in the fan-shaped body to encode the decision before relay to downstream motor circuits for behavioral implementation. Our results uncover a novel role for the fan-shaped body in choice encoding, and reveal a neural substrate for sensory and internal state integration for decision making in a genetically tractable model organism to enable mechanistic dissection at circuit, cellular, and molecular levels.</jats:p

Limited cognitive resources explain a trade-off between perceptual and metacognitive vigilance

© 2017 the authors. Why do experimenters give subjects short breaks in long behavioral experiments? Whereas previous studies suggest it is difficult to maintain attention and vigilance over long periods of time, it is unclear precisely what mechanisms benefit from rest after short experimental blocks. Here, we evaluate decline in both perceptual performance and metacognitive sensitivity (i.e., how well confidence ratings track perceptual decision accuracy) over time and investigate whether characteristics of prefrontal cortical areas correlate with these measures. Whereas a single-process signal detection model predicts that these two forms of fatigue should be strongly positively correlated, a dual-process model predicts that rates of decline may dissociate. Here, we show that these measures consistently exhibited negative or near-zero correlations, as if engaged in a trade-off relationship, suggesting that different mechanisms contribute to perceptual and metacognitive decisions. Despite this dissociation, the two mechanisms likely depend on common resources, which could explain their trade-off relationship. Based on structural MRI brain images of individual human subjects, we assessed gray matter volume in the frontal polar area, a region that has been linked to visual metacognition. Variability of frontal polar volume correlated with individual differences in behavior, indicating the region may play a role in supplying common resources for both perceptual and metacognitive vigilance. Additional experiments revealed that reduced metacognitive demand led to superior perceptual vigilance, providing further support for this hypothesis. Overall, results indicate that during breaks between short blocks, it is the higher-level perceptual decision mechanisms, rather than lower-level sensory machinery, that benefit most from rest.Link_to_subscribed_fulltex