Patterns of retrieval-related cortico-striatal connectivity are stable across the adult lifespan.

Memory retrieval effects in the striatum are well documented and robust across experimental paradigms. However, the functional significance of these effects, and whether they are moderated by age, remains unclear. We used functional magnetic resonance imaging paired with an associative recognition task to examine retrieval effects in the striatum in a sample of healthy young, middle-aged, and older adults. We identified anatomically segregated patterns of enhanced striatal blood oxygen level-dependent (BOLD) activity during recollection- and familiarity-based memory judgments. Successful recollection was associated with enhanced BOLD activity in bilateral putamen and nucleus accumbens, and neither of these effects were reliably moderated by age. Familiarity effects were evident in the head of the caudate nucleus bilaterally, and these effects were attenuated in middle-aged and older adults. Using psychophysiological interaction analyses, we observed a monitoring-related increase in functional connectivity between the caudate and regions of the frontoparietal control network, and between the putamen and bilateral retrosplenial cortex and intraparietal sulcus. In all instances, monitoring-related increases in cortico-striatal connectivity were unmoderated by age. These results suggest that the striatum, and the caudate in particular, couples with the frontoparietal control network to support top-down retrieval-monitoring operations, and that the strength of these inter-regional interactions is preserved in later life.

The Retrieval-Related Anterior Shift Is Moderated by Age and Correlates with Memory Performance.

Recent research suggests that episodic memory is associated with systematic differences in the localization of neural activity observed during memory encoding and retrieval. The retrieval-related anterior shift is a phenomenon whereby the retrieval of a stimulus event (e.g., a scene image) is associated with a peak neural response which is localized more anteriorly than the response elicited when the stimulus is experienced directly. Here, we examine whether the magnitude of the anterior shift (i.e., the distance between encoding- and retrieval-related response peaks) is moderated by age, and also whether the shift is associated with memory performance. Younger and older human subjects of both sexes underwent fMRI as they completed encoding and retrieval tasks on word-face and word-scene pairs. We localized peak scene and face selectivity for each individual participant within the face-selective precuneus and in three scene-selective (parahippocampal place area [PPA], medial place area, occipital place area) ROIs. In line with recent findings, we identified an anterior shift in the PPA and occipital place area in both age groups and, in older adults only, in the medial place area and precuneus also. Of importance, the magnitude of the anterior shift was larger in older than in younger adults. The shift within the PPA exhibited an age-invariant across-participant negative correlation with source memory performance, such that a smaller displacement between encoding- and retrieval-related neural activity was associated with better performance. These findings provide novel insights into the functional significance of the anterior shift, especially in relation to memory decline in older age.SIGNIFICANCE STATEMENT Cognitive aging is associated with reduced ability to retrieve precise details of previously experienced events. The retrieval-related anterior shift is a phenomenon in which category-selective cortical activity at retrieval is localized anterior to the peak activity at encoding. The shift is thought to reflect a bias at retrieval in favor of semantic and abstract information at the expense of low-level perceptual detail. Here, we report that the anterior shift is exaggerated in older relative to younger adults, and we demonstrate that a larger shift in the parahippocampal place area is associated with poorer memory performance. These findings suggest that the shift is sensitive to increasing age and that it is moderated by the quality and content of the retrieved episode.

Quality Improvement Report: Design and Implementation of a Radiology E-Consult Service.

Electronic consultations (e-consults) mediated through an electronic health record system or web-based platform allow synchronous or asynchronous physician-to-physician communication. E-consults have been explored in various clinical specialties, but relatively few instances in the literature describe e-consults to connect health care providers directly with radiologists.The authors outline how a radiology department can implement an e-consult service and review the development of such a service in a large academic health system. They describe the logistics, workflow, turnaround time expectations, stakeholder management, and pilot implementation and highlight challenges and lessons learned.

Distinct neurophysiological correlates of the fMRI BOLD signal in the hippocampus and neocortex.

Functional magnetic resonance imaging (fMRI) is among the foremost methods for mapping human brain function but provides only an indirect measure of underlying neural activity. Recent findings suggest that the neurophysiological correlates of the fMRI blood-oxygen-level-dependent (BOLD) signal might be regionally specific. We examined the neurophysiological correlates of the fMRI BOLD signal in the hippocampus and neocortex, where differences in neural architecture might result in a different relationship between the respective signals. Fifteen human neurosurgical patients (10 female, 5 male) implanted with depth electrodes performed a verbal free recall task while electrophysiological activity was recorded simultaneously from hippocampal and neocortical sites. The same patients subsequently performed a similar version of the task during a later fMRI session. Subsequent memory effects (SMEs) were computed for both imaging modalities as patterns of encoding-related brain activity predictive of later free recall. Linear mixed-effects modelling revealed that the relationship between BOLD and gamma-band SMEs was moderated by the lobar location of the recording site. BOLD and high gamma (70-150 Hz) SMEs positively covaried across much of the neocortex. This relationship was reversed in the hippocampus, where a negative correlation between BOLD and high gamma SMEs was evident. We also observed a negative relationship between BOLD and low gamma (30-70 Hz) SMEs in the medial temporal lobe more broadly. These results suggest that the neurophysiological correlates of the BOLD signal in the hippocampus differ from those observed in the neocortex.Significance Statement:The blood-oxygen-level-dependent (BOLD) signal forms the basis of fMRI but provides only an indirect measure of neural activity. Task-related modulation of BOLD signals are typically equated with changes in gamma-band activity; however, relevant empirical evidence comes largely from the neocortex. We examined neurophysiological correlates of the BOLD signal in the hippocampus, where the differing neural architecture might result in a different relationship between the respective signals. We identified a positive relationship between encoding-related changes in BOLD and gamma-band activity in frontal and parietal cortex. This effect was reversed in the hippocampus, where BOLD and gamma-band effects negatively covaried. These results suggest regional variability in the transfer function between neural activity and the BOLD signal in the hippocampus and neocortex.

Rewriting yeast central carbon metabolism for industrial isoprenoid production.

A bio-based economy has the potential to provide sustainable substitutes for petroleum-based products and new chemical building blocks for advanced materials. We previously engineered Saccharomyces cerevisiae for industrial production of the isoprenoid artemisinic acid for use in antimalarial treatments. Adapting these strains for biosynthesis of other isoprenoids such as ß-farnesene (C15H24), a plant sesquiterpene with versatile industrial applications, is straightforward. However, S. cerevisiae uses a chemically inefficient pathway for isoprenoid biosynthesis, resulting in yield and productivity limitations incompatible with commodity-scale production. Here we use four non-native metabolic reactions to rewire central carbon metabolism in S. cerevisiae, enabling biosynthesis of cytosolic acetyl coenzyme A (acetyl-CoA, the two-carbon isoprenoid precursor) with a reduced ATP requirement, reduced loss of carbon to CO2-emitting reactions, and improved pathway redox balance. We show that strains with rewired central metabolism can devote an identical quantity of sugar to farnesene production as control strains, yet produce 25% more farnesene with that sugar while requiring 75% less oxygen. These changes lower feedstock costs and dramatically increase productivity in industrial fermentations which are by necessity oxygen-constrained. Despite altering key regulatory nodes, engineered strains grow robustly under taxing industrial conditions, maintaining stable yield for two weeks in broth that reaches >15% farnesene by volume. This illustrates that rewiring yeast central metabolism is a viable strategy for cost-effective, large-scale production of acetyl-CoA-derived molecules.

Age Differences In Retrieval-Related Reinstatement Reflect Age-Related Dedifferentiation At Encoding.

Age-related reductions in neural selectivity have been linked to cognitive decline. We examined whether age differences in the strength of retrieval-related cortical reinstatement could be explained by analogous differences in neural selectivity at encoding, and whether reinstatement was associated with memory performance in an age-dependent or an age-independent manner. Young and older adults underwent fMRI as they encoded words paired with images of faces or scenes. During a subsequent scanned memory test participants judged whether test words were studied or unstudied and, for words judged studied, also made a source memory judgment about the associated image category. Using multi-voxel pattern similarity analyses, we identified robust evidence for reduced scene reinstatement in older relative to younger adults. This decline was however largely explained by age differences in neural differentiation at encoding; moreover, a similar relationship between neural selectivity at encoding and retrieval was evident in young participants. The results suggest that, regardless of age, the selectivity with which events are neurally processed at the time of encoding can determine the strength of retrieval-related cortical reinstatement.

Field aging declines the regulatory effects of biochar on cadmium uptake by pepper in the soil.

Biochar application is not only being widely promoted as an ideal strategy to mitigate global climate warming, but it also has the advantage of reducing heavy metal bioavailability and migration in the soil. However, studies on the effects of field aging on biochar to reduce heavy metals from the soil are still limited. The present study aimed to explore the effects and mechanisms of aged biochar added to the soil planted with pepper plants on cadmium (Cd) uptake. To achieve this, un-amended soil (control), soil amended with fresh biochar, and aged biochar (biochar recovered from a long-term field trial after 9 years) were used to investigate the effects of field aging on biochar adsorption efficiency. The results revealed that the amount of Cd in the plant planted in control soil, amended with fresh and aged biochar, accounted for 40 ± 6.10, 17.18 ± 1.19, and 18.68 ± 0.79, respectively. There was a significant difference (P < 0.05) in the amount of Cd that was uptaken by plants among all treatments. However, soil amended with fresh biochar significantly (P < 0.05) decreased the amount of Cd in plants compared with soil amended with aged biochar. This indicates that field aging declines the potential of biochar to lower heavy metal bioavailability and retention in the soil. This study demonstrates that long-term burial lessens the ability of biochar to interact with Cd and suggests that biochar amendment can lower Cd in the soil, depending on the freshness and aging of biochar.

High precision integrated photonic thermometry enabled by a transfer printed diamond resonator on GaN waveguide chip.

We demonstrate a dual-material integrated photonic thermometer, fabricated by high accuracy micro-transfer printing. A freestanding diamond micro-disk resonator is printed in close proximity to a gallium nitride on a sapphire racetrack resonator, and respective loaded Q factors of 9.1 × 104 and 2.9 × 104 are measured. We show that by using two independent wide-bandgap materials, tracking the thermally induced shifts in multiple resonances, and using optimized curve fitting tools the measurement error can be reduced to 9.2 mK. Finally, for the GaN, in a continuous acquisition measurement we record an improvement in minimum Allan variance, occurring at an averaging time four times greater than a comparative silicon device, indicating better performance over longer time scales.

Comparison of fMRI correlates of successful episodic memory encoding in temporal lobe epilepsy patients and healthy controls.

Intra-cranial electroencephalographic brain recordings (iEEG) provide a powerful tool for investigating the neural processes supporting episodic memory encoding and form the basis of experimental therapies aimed at improving memory dysfunction. However, given the invasiveness of iEEG, investigations are constrained to patients with drug-resistant epilepsy for whom such recordings are clinically indicated. Particularly in the case of temporal lobe epilepsy (TLE), neuropathology and the possibility of functional reorganization are potential constraints on the generalizability of intra-cerebral findings and pose challenges to the development of therapies for memory disorders stemming from other etiologies. Here, samples of TLE (N â€‹= â€‹16; all of whom had undergone iEEG) and age-matched healthy control (N â€‹= â€‹19) participants underwent fMRI as they studied lists of concrete nouns. fMRI BOLD responses elicited by the study words were segregated according to subsequent performance on tests of delayed free recall and recognition memory. Subsequent memory effects predictive of both successful recall and recognition memory were evident in several neural regions, most prominently in the left inferior frontal gyrus, and did not demonstrate any group differences. Behaviorally, the groups did not differ in overall recall performance or in the strength of temporal contiguity effects. However, group differences in serial position effects and false alarm rates were evident during the free recall and recognition memory tasks, respectively. Despite these behavioral differences, neuropathology associated with temporal lobe epilepsy was apparently insufficient to give rise to detectable differences in the functional neuroanatomy of episodic memory encoding relative to neurologically healthy controls. The findings provide reassurance that iEEG findings derived from experimental paradigms similar to those employed here generalize to the neurotypical population.

Clean manufacturing powered by biology: how Amyris has deployed technology and aims to do it better.

Amyris is a fermentation product company that leverages synthetic biology and has been bringing novel fermentation products to the market since 2009. Driven by breakthroughs in genome editing, strain construction and testing, analytics, automation, data science, and process development, Amyris has commercialized nine separate fermentation products over the last decade. This has been accomplished by partnering with the teams at 17 different manufacturing sites around the world. This paper begins with the technology that drives Amyris, describes some key lessons learned from early scale-up experiences, and summarizes the technology transfer procedures and systems that have been built to enable moving more products to market faster. Finally, the breadth of the Amyris product portfolio continues to expand; thus the steps being taken to overcome current challenges (e.g. automated strain engineering can now outpace the rest of the product commercialization timeline) are described.

Angiosperm symbioses with non-mycorrhizal fungal partners enhance N acquisition from ancient organic matter in a warming maritime Antarctic.

In contrast to the situation in plants inhabiting most of the world's ecosystems, mycorrhizal fungi are usually absent from roots of the only two native vascular plant species of maritime Antarctica, Deschampsia antarctica and Colobanthus quitensis. Instead, a range of ascomycete fungi, termed dark septate endophytes (DSEs), frequently colonise the roots of these plant species. We demonstrate that colonisation of Antarctic vascular plants by DSEs facilitates not only the acquisition of organic nitrogen as early protein breakdown products, but also as non-proteinaceous d-amino acids and their short peptides, accumulated in slowly-decomposing organic matter, such as moss peat. Our findings suggest that, in a warming maritime Antarctic, this symbiosis has a key role in accelerating the replacement of formerly dominant moss communities by vascular plants, and in increasing the rate at which ancient carbon stores laid down as moss peat over centuries or millennia are returned to the atmosphere as CO2 .

Plant-microbe competition: does injection of isotopes of C and N into the rhizosphere effectively characterise plant use of soil N?

Despite considerable attention over the last 25 yr, the importance of early protein breakdown products to plant nitrogen (N) nutrition remains uncertain. We used rhizosphere injection of 15 N-, 13 C- and 14 C-labelled inorganic N and amino acid (l-alanine), with chase periods from 1 min to 24 h, to investigate the duration of competition for amino acid between roots (Triticum aestivum) and soil microorganisms. We further investigated how microbial modification of l-alanine influenced plant carbon (C) and N recovery. From recovery of C isotopes, intact alanine uptake was 0.2-1.3% of added. Soil microbes appeared to remove alanine from soil solution within 1 min and release enough NH4+ to account for all plant 15 N recovery (over 24 h) within 5 min. Microbially generated inorganic or keto acid C accounted for < 25% of the lowest estimate of intact alanine uptake. Co-location of C and N labels appears a reasonable measure of intact uptake. Potential interference from microbially modified C is probably modest, but may increase with chase period. Similarly, competition for l-alanine is complete within a few minutes in soil, whereas NO3- added at the same rate is available for > 24 h, indicating that long chase periods bias outcomes and fail to accurately simulate soil processes.

Elucidation of non-intentionally added substances migrating from polyester-polyurethane lacquers using automated LC-HRMS data processing.

An untargeted strategy aiming at identifying non-intentionally added substances (NIAS) migrating from coatings was developed. This innovative approach was applied to two polyester-polyurethane lacquers, for which suppliers previously provided the identity of the monomers involved. Lacquers were extracted with acetonitrile and analyzed by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Data, acquired in the full scan mode, were processed using an open-source R-environment (xcms and CAMERA packages) to list the detected features and deconvolute them in groups related to individual compounds. The most intense groups, accounting for more than 85% of cumulated feature intensities, were then investigated. A homemade database, populated with predicted polyester oligomer combinations from a relevant selection of diols and diacids, enabled highlighting the presence of 14 and 17 cyclic predicted polyester oligomers in the two lacquers, including three mutual combinations explained by common known monomers. Combination hypotheses were strengthened by chromatographic considerations and by the investigation of fragmentation patterns. Regarding unpredicted migrating substances, four monomers were hypothesised to explain several polyester or caprolactam oligomer series. Finally, considering both predicted and tentatively elucidated unpredicted oligomers, it was possible to assign hypotheses to features representing up to 82% and 90% of the cumulated intensities in the two lacquers, plus 9% and 3% (respectively) originating from the procedural blank. Graphical abstract Elucidation of non-intentionally added substances.

Modified High-Molecular-Weight Hyaluronan Promotes Allergen-Specific Immune Tolerance.

The extracellular matrix in asthmatic lungs contains abundant low-molecular-weight hyaluronan, and this is known to promote antigen presentation and allergic responses. Conversely, high-molecular-weight hyaluronan (HMW-HA), typical of uninflamed tissues, is known to suppress inflammation. We investigated whether HMW-HA can be adapted to promote tolerance to airway allergens. HMW-HA was thiolated to prevent its catabolism and was tethered to allergens via thiol linkages. This platform, which we call "XHA," delivers antigenic payloads in the context of antiinflammatory costimulation. Allergen/XHA was administered intranasally to mice that had been sensitized previously to these allergens. XHA prevents allergic airway inflammation in mice sensitized previously to either ovalbumin or cockroach proteins. Allergen/XHA treatment reduced inflammatory cell counts, airway hyperresponsiveness, allergen-specific IgE, and T helper type 2 cell cytokine production in comparison with allergen alone. These effects were allergen specific and IL-10 dependent. They were durable for weeks after the last challenge, providing a substantial advantage over the current desensitization protocols. Mechanistically, XHA promoted CD44-dependent inhibition of nuclear factor-κB signaling, diminished dendritic cell maturation, and reduced the induction of allergen-specific CD4 T-helper responses. XHA and other potential strategies that target CD44 are promising alternatives for the treatment of asthma and allergic sinusitis.

Neural congruence between intertemporal and interpersonal self-control: Evidence from delay and social discounting.

Behavioral studies using delay and social discounting as indices of self-control and altruism, respectively, have revealed functional similarities between farsighted and social decisions. However, neural evidence for this functional link is lacking. Twenty-five young adults completed a delay and social discounting task during fMRI scanning. A spatiotemporal partial least squares analysis revealed that both forms of discounting were well characterized by a pattern of brain activity in areas comprising frontoparietal control, default, and mesolimbic reward networks. Both forms of discounting appear to draw on common neurocognitive mechanisms, regardless of whether choices involve intertemporal or interpersonal outcomes. We also observed neural profiles differentiating between high and low discounters. High discounters were well characterized by increased medial temporal lobe and limbic activity. In contrast, low discount rates were associated with activity in the medial prefrontal cortex and right temporoparietal junction. This pattern may reflect biological mechanisms underlying behavioral heterogeneity in discount rates.

Clinical Importance and Natural History of Biliary Sludge in Outpatients.

OBJECTIVES: Gallbladder sludge is a common diagnosis on routine abdominal sonography, yet its clinical importance is uncertain, especially in outpatients. To determine its natural history and potential future complications in this setting, we reviewed the imaging and clinical histories of nonhospitalized patients with a diagnosis of sludge on sonography. METHODS: We conducted a retrospective search of our institutional radiology information system for all sonographic reports using the key words "biliary sludge without gallstones" over a 3-year period. For each of the 104 patients with isolated biliary sludge on initial sonography, we reviewed the electronic medical records and all imaging for the development of pancreaticobiliary complications. RESULTS: We found an overall prevalence of biliary sludge in outpatients of 1.8%. Of the 104 patients reviewed with a mean follow up of 630 days (21 months), 25 developed a pancreaticobiliary complication, including cholelithiasis, cholecystitis, choledocholithiasis, and pancreatitis. The most frequent complication was cholecystitis, with a total of 14 diagnoses (12 chronic acalculous and 2 acute with gallstones). An additional 6 patients developed gallstones without cholecystitis features; 4 patients developed pancreatitis; and 1 developed choledocholithiasis. Biliary sludge remained quiescent or resolved in 76% of patients. CONCLUSIONS: Biliary sludge always represents a pathologic process, but its clinical implications among outpatients have not been previously investigated. Our ambulatory population developed pancreaticobiliary complications at similar rates as prior mixed-patient setting studies. Regardless of the patient setting, biliary sludge is likely of more clinical importance than previously regarded.

Living roots magnify the response of soil organic carbon decomposition to temperature in temperate grassland.

Increasing atmospheric carbon dioxide (CO2 ) concentration is both a strong driver of primary productivity and widely believed to be the principal cause of recent increases in global temperature. Soils are the largest store of the world's terrestrial C. Consequently, many investigations have attempted to mechanistically understand how microbial mineralisation of soil organic carbon (SOC) to CO2 will be affected by projected increases in temperature. Most have attempted this in the absence of plants as the flux of CO2 from root and rhizomicrobial respiration in intact plant-soil systems confounds interpretation of measurements. We compared the effect of a small increase in temperature on respiration from soils without recent plant C with the effect on intact grass swards. We found that for 48 weeks, before acclimation occurred, an experimental 3 °C increase in sward temperature gave rise to a 50% increase in below ground respiration (ca. 0.4 kg C m(-2) ; Q10  = 3.5), whereas mineralisation of older SOC without plants increased with a Q10 of only 1.7 when subject to increases in ambient soil temperature. Subsequent (14) C dating of respired CO2 indicated that the presence of plants in swards more than doubled the effect of warming on the rate of mineralisation of SOC with an estimated mean C age of ca. 8 years or older relative to incubated soils without recent plant inputs. These results not only illustrate the formidable complexity of mechanisms controlling C fluxes in soils but also suggest that the dual biological and physical effects of CO2 on primary productivity and global temperature have the potential to synergistically increase the mineralisation of existing soil C.

Epistasis analysis with global transcriptional phenotypes.

Classical epistasis analysis can determine the order of function of genes in pathways using morphological, biochemical and other phenotypes. It requires knowledge of the pathway's phenotypic output and a variety of experimental expertise and so is unsuitable for genome-scale analysis. Here we used microarray profiles of mutants as phenotypes for epistasis analysis. Considering genes that regulate activity of protein kinase A in Dictyostelium, we identified known and unknown epistatic relationships and reconstructed a genetic network with microarray phenotypes alone. This work shows that microarray data can provide a uniform, quantitative tool for large-scale genetic network analysis.

Neural correlates of retrieval success and precision: an fMRI study.

Prior studies examining the neural mechanisms underlying retrieval success and precision have yielded inconsistent results. Here, their neural correlates were examined using a memory task that assessed precision for spatial location. A sample of healthy young adults underwent fMRI scanning during a single study-test cycle. At study, participants viewed a series of object images, each placed at a randomly selected location on an imaginary circle. At test, studied images were intermixed with new images and presented to the participants. The requirement was to move a cursor to the location of the studied image, guessing if necessary. Participants then signaled whether the presented image as having been studied. Memory precision was quantified as the angle between the studied location and the location selected by the participant. A precision effect was evident in the left angular gyrus, where BOLD activity covaried across trials with location accuracy. Multi-voxel pattern analysis also revealed a significant item-level reinstatement effect for high-precision trials. There was no evidence of a retrieval success effect in the angular gyrus. BOLD activity in the hippocampus was insensitive to both success and precision. These findings are partially consistent with prior evidence that success and precision are dissociable features of memory retrieval.

Age differences in spatial memory are mitigated during naturalistic navigation.

Spatial navigation deficits are often observed among older adults on tasks that require navigating virtual reality (VR) environments on a computer screen. We investigated whether these age differences are attenuated when tested in more naturalistic and ambulatory virtual environments. In Experiment 1, young and older adults navigated a variant of the Morris Water Maze task in each of two VR conditions: a desktop VR condition which required using a mouse and keyboard to navigate, and an ambulatory VR condition which permitted unrestricted locomotion. In Experiment 2, we examined whether age- and VR-related differences in spatial performance were affected by the inclusion of additional spatial cues. In both experiments, older adults navigated to target locations less precisely than younger individuals in the desktop condition. Age differences were significantly attenuated, however, when tested in the ambulatory VR environment. These findings underscore the importance of developing naturalistic assessments of spatial memory and navigation.