Advantageous foraging choices benefit from an estimation of two aspects of a resource’s value: its current desirability and availability. Both orbitofrontal and ventrolateral prefrontal areas ...contribute to updating these valuations, but their precise roles remain unclear. To explore their specializations, we trained macaque monkeys on two tasks: one required updating representations of a predicted outcome’s desirability, as adjusted by selective satiation, and the other required updating representations of an outcome’s availability, as indexed by its probability. We evaluated performance on both tasks in three groups of monkeys: unoperated controls and those with selective, fiber-sparing lesions of either the OFC or VLPFC. Representations that depend on the VLPFC but not the OFC play a necessary role in choices based on outcome availability; in contrast, representations that depend on the OFC but not the VLPFC play a necessary role in choices based on outcome desirability.
•The VLPFC is necessary for updating stimulus-outcome probability estimates•The OFC is necessary for updating stimulus-outcome values based on current needs•The VLPFC is necessary for both contingent and noncontingent learning
Rudebeck et al. show that the orbitofrontal cortex (OFC) and ventrolateral prefrontal cortex (VLPFC) make dissociable contributions to decision-making. The VLPFC, but not the OFC, is critical for updating stimulus-outcome availability, whereas the OFC, but not the VLPFC, is vital for updating stimulus-outcome desirability.
Context. In the recent literature there has been some doubt as to the reliability of CO multi-transitional line observations as a mass-loss-rate estimator for AGB stars. Aims. Using new ...well-calibrated CO radio line observations, the main aim of the work presented here is to carefully evaluate the reliability of CO mass-loss-rate estimates for intermediate- to high-mass-loss-rate AGB stars with different photospheric chemistries. Methods. Mass-loss rates for 10 intermediate- to high-mass-loss-rate AGB stars are derived using a detailed non-LTE, non-local radiative transfer code based on the Monte-Carlo method to model the CO radio line intensities. The circumstellar envelopes are assumed to be spherically symmetric and formed by constant mass-loss rates. The energy balance is solved self-consistently and the effects of dust on the radiation field and thermal balance included. An independent estimate of the mass-loss rate is also obtained from the combination of dust radiative transfer modelling with a dynamical model of the gas and dust particles. Results. We find that the CO radio line intensities and shapes are successfully reproduced for the majority of our objects when assuming a constant mass-loss rate. Moreover, the CO line intensities are only weakly dependent on the adopted micro-turbulent velocity, in contrast to recent claims in the literature. The two methods used in the present work to derive mass-loss rates are consistent within a factor of ~3 for intermediate- to high-mass-loss-rate objects, indicating that this is a lower limit to the uncertainty in present mass-loss-rate estimates. We find a tentative trend with chemistry. Mass-loss rates from the dust/dynamical model are systematically higher than those from the CO model for the carbon stars and vice versa for the M-type stars. This could be ascribed to a discrepancy in the adopted CO/H2-abundance ratio, but we caution that the sample is small and systematic errors cannot be excluded.
Designed as a high-capacity alloy host for Na-ion chemistry, a forest of Sn nanorods with a unique core–shell structure was synthesized on viral scaffolds, which were genetically engineered to ensure ...a nearly vertical alignment upon self-assembly onto a metal substrate. The interdigital spaces thus formed between individual rods effectively accommodated the volume expansion and contraction of the alloy upon sodiation/desodiation, while additional carbon-coating engineered over these nanorods further suppressed Sn aggregation during extended electrochemical cycling. Due to the unique nanohierarchy of multiple functional layers, the resultant 3D nanoforest of C/Sn/Ni/TMV1cys, binder-free composite electrode already and evenly assembled on a stainless steel current collector, exhibited supreme capacity utilization and cycling stability toward Na-ion storage and release. An initial capacity of 722 mA·h (g Sn)−1 along with 405 mA·h (g Sn)−1 retained after 150 deep cycles demonstrates the longest-cycling nano-Sn anode material for Na-ion batteries reported in the literature to date and marks a significant performance improvement for neat Sn material as alloy host for Na-ion chemistry.
The output of gravitational-wave interferometers, such as LIGO and Virgo, can be highly non-stationary. Broadband detector noise can affect the detector sensitivity on the order of tens of seconds. ...Gravitational-wave transient searches, such as those for colliding black holes, estimate this noise in order to identify gravitational-wave events. During times of non-stationarity we see a higher rate of false events being reported. To accurately separate signal from noise, it is imperative to incorporate the changing detector state into gravitational-wave searches. We develop a new statistic which estimates the variation of the interferometric detector noise. We use this statistic to re-rank candidate events identified during LIGO-Virgo's second observing run by the PyCBC search pipeline. This results in a 5% improvement in the sensitivity volume for low mass binaries, particularly binary neutron stars mergers.
Superoxide is a reactive oxygen species produced during aerobic metabolism in mitochondria and prokaryotes. It causes damage to lipids, proteins and DNA and is implicated in cancer, cardiovascular ...disease, neurodegenerative disorders and aging. As protection, cells express soluble superoxide dismutases, disproportionating superoxide to oxygen and hydrogen peroxide. Here, we describe a membrane-bound enzyme that directly oxidizes superoxide and funnels the sequestered electrons to ubiquinone in a diffusion-limited reaction. Experiments in proteoliposomes and inverted membranes show that the protein is capable of efficiently quenching superoxide generated at the membrane in vitro. The 2.0 Å crystal structure shows an integral membrane di-heme cytochrome b poised for electron transfer from the P-side and proton uptake from the N-side. This suggests that the reaction is electrogenic and contributes to the membrane potential while also conserving energy by reducing the quinone pool. Based on this enzymatic activity, we propose that the enzyme family be denoted superoxide oxidase (SOO).
Somatic mutations have a central role in cancer, but there are also a few rare autoimmune diseases in which somatic mutations play a major role. We have recently shown that nonsynonymous somatic ...mutations with low allele fractions are preferentially detectable in CD8+ cells and that the STAT3 gene is a promising target for screening. Here, we analyzed somatic mutations in the STAT3 SH2 domain in peripheral blood CD8+ cells in a set of 94 multiple sclerosis (MS) patients and 99 matched controls. PCR amplicons targeting the exons 20 and 21 of STAT3 were prepared and sequenced using the Illumina MiSeq instrument with 2x300bp reads. We designed a novel variant calling method, optimized for large number of samples, high sequencing depth (>25,000x) and small target genomic area. Overall, we discovered 64 STAT3 somatic mutations in the 193 donors, of which 63 were non-synonymous and 77% have been previously reported in cancer or lymphoproliferative disease. The overall median variant allele fraction was 0.065% (range 0.007-1.2%), without significant difference between MS and controls (p = 0.82). There were 26 (28%) MS patients vs. 24 (24%) controls with mutations (p = 0.62). Two or more mutations were found in 9 MS patients vs. 2 controls (p = 0.03, pcorr = 0.12). Carriership of mutations associated with older age and lower neutrophil counts. These results demonstrate that STAT3 SH2 domain is a hotspot for somatic mutations in CD8+ cells with a prevalence of 26% among the participants. There were no significant differences in the mutation prevalences between MS patients and controls. Further research is needed to elucidate the role of antigenic stimuli in the expansion of the mutant clones. Furthermore, the high discovered prevalence of STAT3 somatic mutations makes it feasible to analyze these mutations directly in tissue-infiltrating CD8+ cells in autoimmune diseases.
The very-long-chain fatty acyl-CoA synthetase FadD13 from Mycobacterium tuberculosis activates fatty acids for further use in mycobacterial lipid metabolism. FadD13 is a peripheral membrane protein, ...with both soluble and membrane-bound populations in vivo. The protein displays a distinct positively charged surface patch, suggested to be involved in membrane association. In this paper, we combine structural analysis with liposome co-flotation assays and membrane association modeling to gain a more comprehensive understanding of the mechanisms behind membrane association. We show that FadD13 has affinity for negatively charged lipids, such as cardiolipin. Addition of a fatty acid substrate to the liposomes increases the apparent affinity of FadD13, consistent with our previous hypothesis that FadD13 can utilize the membrane to harbor its very-long-chain fatty acyl substrates. In addition, we unambiguously show that FadD13 adopts a dimeric arrangement in solution. The dimer interface partly buries the positive surface patch, seemingly inconsistent with membrane binding. Notably, when cross-linking the dimer, it lost its ability to bind and co-migrate with liposomes. To better understand the dynamics of association, we utilized two mutant variants of FadD13, one in which the positively charged patch was altered to become more negative and one more hydrophobic. Both variants were predominantly monomeric in solution. The hydrophobic variant maintained the ability to bind to the membrane, whereas the negative variant did not. Taken together, our data indicate that FadD13 exists in a dynamic equilibrium between the dimer and monomer, where the monomeric state can adhere to the membrane via the positively charged surface patch.
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