Patterns Of Metabolic Activity Research Articles

Synergistic Effects of Salicylic Acid and Bacillus butanolivorans KJ40 for Enhancing Napa Cabbage (Brassica napa subsp. pekinensis) Resilience to Water-Deficit Stress

Climate change exacerbates drought, globally impacting crop production and necessitating the adoption of sustainable strategies. This study investigates the potential synergistic effects of salicylic acid (SA) and Bacillus butanolivorans KJ40 (KJ40) on napa cabbage (Brassica rapa subsp. pekinensis) under water-deficit stress conditions by watering withheld for five days. Results demonstrate that the combined application of KJ40 and SA, particularly at concentrations of 0.5 mM and 1 mM, significantly enhances plant growth and mitigates the negative impacts of water deficit. Moreover, the combination treatment with SA (0.5 mM) and KJ40 (1 × 108 cells/mL) reduces lipid oxidation and enhances antioxidant enzyme activity, indicating improved plant stress tolerance. Analysis of soil microbial profiles reveals alterations in metabolic activity and substrate utilization patterns, suggesting potential changes in rhizosphere dynamics. Additionally, this study examines the impact of SA on KJ40 population dynamics in soil, revealing concentration-dependent effects on bacterial survival. Overall, the combination of KJ40 and SA was effective in mitigating water-deficit stress in napa cabbage. These findings highlight the combination as a novel synergistic strategy to enhance plant resilience to water-deficit stress, offering insights into plant–microbe interactions and soil ecosystem dynamics.

Is 18F-FDG-PET/CT an Optimal Imaging Modality for Detecting Immune-Related Adverse Events after Immune-Checkpoint Inhibitor Therapy? Pros and Cons.

Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized contemporary oncology, presenting efficacy in various solid tumors and lymphomas. However, ICIs may potentially overstimulate the immune system, leading to immune-related adverse events (irAEs). IrAEs may affect multiple organs, such as the colon, stomach, small intestine, kidneys, skin, lungs, joints, liver, lymph nodes, bone marrow, brain, heart, and endocrine glands (e.g., pancreas, thyroid, or adrenal glands), exhibiting autoimmune inflammation. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is commonly used in oncology for staging and assessment of therapy responses, but it may also serve as a tool for detecting irAEs. This review aims to present various patterns of metabolic activation associated with irAEs due to ICI treatment, identifiable through 18F-FDG PET/CT. It describes the advantages of early detection of irAEs, but also presents the challenges in differentiating them from tumor progression. It also delves into aspects of molecular response assessment within the context of pseudoprogression and hyperprogression, along with typical imaging findings related to these phenomena. Lastly, it summarizes the role of functional PET imaging in oncological immunotherapy, speculating on its future significance and limitations.

Functional analysis and transcriptome profile of meninges and skin fibroblasts from human-aged donors.

The central nervous system (CNS) is surrounded by three membranes called meninges. Specialised fibroblasts, originating from the mesoderm and neural crest, primarily populate the meninges and serve as a binding agent. Our goal was to compare fibroblasts from meninges and skin obtained from the same human-aged donors, exploring their molecular and cellular characteristics related to CNS functions. We isolated meningeal fibroblasts (MFs) from brain donors and skin fibroblasts (SFs) from the same subjects. A functional analysis was performed measuring cell appearance, metabolic activity, and cellular orientation. We examined fibronectin, serpin H1, β-III-tubulin, and nestin through qPCR and immunofluorescence. A whole transcriptome analysis was also performed to characterise the gene expression of MFs and SFs. MFs appeared more rapidly in the post-tissue processing, while SFs showed an elevated cellular metabolism and a well-defined cellular orientation. The four markers were mostly similar between the MFs and SFs, except for nestin, more expressed in MFs. Transcriptome analysis reveals significant differences, particularly in cyclic adenosine monophosphate (cAMP) metabolism and response to forskolin, both of which are upregulated in MFs. This study highlights MFs' unique characteristics, including the timing of appearance, metabolic activity, and gene expression patterns, particularly in cAMP metabolism and response to forskolin. These findings contribute to a deeper understanding of non-neuronal cells' involvement in CNS activities and potentially open avenues for therapeutic exploration.

Distinct patterns of metabolic motor cortex activity for phantom and residual limb pain in people with amputations: A functional near-infrared spectroscopy study

BackgroundPhantom pain limb (PLP) has gained more attention due to the large number of people with amputations around the world and growing knowledge of the pain process, although its mechanisms are not completely understood. ObjectivesThe aim of this study was to understand, in patients with amputations, the association between PLP and residual limb pain (RLP), and the brain metabolic response in cortical motor circuits, using functional near-infrared spectroscopy (fNIRS). MethodsSixty participants were recruited from the rehabilitation program in São Paulo, Brazil. Included patients were aged over 18 years, with traumatic unilateral lower-limb amputation, with PLP for at least 3 months after full recovery from amputation surgery. PLP and RLP levels were measured using visual analogue scales. fNIRS was performed during motor execution and motor mirror tasks for 20 s. In order to highlight possible variables related to variation in pain measures, univariate linear regression analyses were performed for both experimental conditions, resulting in four fNIRS variables (two hemispheres x two experimental conditions). Later, in order to test the topographic specificity of the models, eight multivariate regression analyses were performed (two pain scales x two experimental conditions x two hemispheres), including the primary motor cortex (PMC) related channel as an independent variable as well as five other channels related to the premotor area, supplementary area, and somatosensory cortex. All models were controlled for age, sex, ethnicity, and education. ResultsWe found that: i) there is an asymmetric metabolic activation during motor execution and mirror task between hemispheres (with a predominance that is ipsilateral to the amputated limb), ii) increased metabolic response in the PMC ipsilateral to the amputation is associated with increased PLP (during both experimental tasks), while increased metabolic response in the contralateral PMC is associated with increased RLP (during the mirror motor task only); ii) increased metabolic activity of the ipsilateral premotor region is associated with increased PLP during the motor mirror task; iii) RLP was only associated with higher metabolic activity in the contralateral PMC and lower metabolic activity in the ipsilateral inferior frontal region during motor mirror task, but PLP was associated with higher metabolic activity during both tasks. ConclusionThese results suggest there is both task and region specificity for the association between the brain metabolic response and the two different types of post-amputation pain. The metabolic predominance that is ipsilateral to the amputated limb during both tasks was associated with higher levels of PLP, suggesting a cortical motor network activity imbalance due to potential interhemispheric compensatory mechanisms. The present work contributes to the understanding of the underlying topographical patterns in the motor-related circuits associated with pain after amputations.

Novel Fabrication of 3-D Cell Laden Micro-Patterned Porous Structure on Cell Growth and Proliferation by Layered Manufacturing.

This study focuses on developing and characterizing a novel 3-dimensional cell-laden micro-patterned porous structure from a mechanical engineering perspective. Tissue engineering holds great promise for repairing damaged organs but faces challenges related to cell viability, biocompatibility, and mechanical strength. This research aims to overcome these limitations by utilizing gelatin methacrylate hydrogel as a scaffold material and employing a photolithography technique for precise patterned fabrication. The mechanical properties of the structure are of particular interest in this study. We evaluate its ability to withstand external forces through compression tests, which provide insights into its strength and stability. Additionally, structural integrity is assessed over time to determine its performance in in vitro and potential in vivo environments. We investigate cell viability and proliferation within the micro-patterned porous structure to evaluate the biological aspects. MTT assays and immunofluorescence staining are employed to analyze the metabolic activity and distribution pattern of cells, respectively. These assessments help us understand the effectiveness of the structure in supporting cell growth and tissue regeneration. The findings of this research contribute to the field of tissue engineering and provide valuable insights for mechanical engineers working on developing scaffolds and structures for regenerative medicine. By addressing challenges related to cell viability, biocompatibility, and mechanical strength, we move closer to realizing clinically viable tissue engineering solutions. The novel micro-patterned porous structure holds promise for applications in artificial organ development and lays the foundation for future advancements in large soft tissue construction.

Cross Attention Transformers for Multi-modal Unsupervised Whole-Body PET Anomaly Detection

Cancer is a highly heterogeneous condition that can occur almost anywhere in the human body. [<sup>18</sup>F]fluorodeoxyglucose Positron Emission Tomography (<sup>18</sup>F-FDG PET) is a imaging modality commonly used to detect cancer due to its high sensitivity and clear visualisation of the pattern of metabolic activity. Nonetheless, as cancer is highly heterogeneous, it is challenging to train general-purpose discriminative cancer detection models, with data availability and disease complexity often cited as a limiting factor. Unsupervised learning methods, more specifically anomaly detection models, have been suggested as a putative solution. These models learn a healthy representation of tissue and detect cancer by predicting deviations from the healthy norm, which requires models capable of accurately learning long-range interactions between organs, their imaging patterns, and other abstract features with high levels of expressivity. Such characteristics are suitably satisfied by transformers, which have been shown to generate state-of-the-art results in unsupervised anomaly detection by training on normal data. This work expands upon such approaches by introducing multi-modal conditioning of the transformer via cross-attention i.e. supplying anatomical reference information from paired CT images to aid the PET anomaly detection task. Furthermore, we show the importance and impact of codebook sizing within a Vector Quantized Variational Autoencoder, on the ability of the transformer network to fulfill the task of anomaly detection. Using 294 whole-body PET/CT samples containing various cancer types, we show that our anomaly detection method is robust and capable of achieving accurate cancer localization results even in cases where normal training data is unavailable. In addition, we show the efficacy of this approach on out-of-sample data showcasing the generalizability of this approach even with limited training data. Lastly, we propose to combine model uncertainty with a new kernel density estimation approach, and show that it provides clinically and statistically significant improvements in accuracy and robustness, when compared to the classic residual-based anomaly maps. Overall, a superior performance is demonstrated against leading state-of-the-art alternatives, drawing attention to the potential of these approaches.

Trophic and Microbial Patterns in the Ross Sea Area (Antarctica): Spatial Variability during the Summer Season

In open regions of the Ross Sea, the role of the microbial community in the turnover of organic matter has scarcely been investigated; indeed, very little is known on how microbial distribution and functional diversity respond to environmental conditions and hydrographic structures. During the austral summer of 2017, two pelagic areas of the Ross Sea [the Drygalski Ice Tongue and the nearby Terra Nova Bay polynya (A area), and the continental Shelf Break area near Cape Adare (C area)] were studied at selected depths [surface, Deep Chlorophyll Maximum (DCM), Circumpolar Deep Water (CDW), deep waters]. Trophic properties [nutrient concentrations, particulate (POC), dissolved organic carbon (DOC) and its optically significant fraction (CDOM) were measured, together with the main hydrological variables. Microbial community abundance [total prokaryotes, living, dead, and actively respiring fraction, high- and low nucleic acid cells (HNA and LNA), pico- and nano-eukaryotes, culturable heterotrophic bacteria], composition, and metabolism (as whole community and as isolated bacteria) were also assessed. Through a multidisciplinary dataset, this study highlighted the variable response of microbial abundance, diversity, and metabolism of the microbial community to the changing local environmental conditions of the Ross Sea. Different forces, such as organic matter inputs (mostly of detrital nature) released from the Drygalski glacier in the A area, and a coastal-to-offshore gradient in the C area, coexisted within this extreme ecosystem. This resulted in a significant spatial segregation of the edaphic parameters, and of the microbial community distribution and metabolic activity patterns.

Climate change leads to higher NPP at the end of the century in the Antarctic Tundra: Response patterns through the lens of lichens

Poikilohydric autotrophs are the main colonizers of the permanent ice-free areas in the Antarctic tundra biome. Global climate warming and the small human footprint in this ecosystem make it especially vulnerable to abrupt changes. Elucidating the effects of climate change on the Antarctic ecosystem is challenging because it mainly comprises poikilohydric species, which are greatly influenced by microtopographic factors. In the present study, we investigated the potential effects of climate change on the metabolic activity and net primary photosynthesis (NPP) in the widespread lichen species Usnea aurantiaco-atra. Long-term monitoring of chlorophyll a fluorescence in the field was combined with photosynthetic performance measurements in laboratory experiments in order to establish the daily response patterns under biotic and abiotic factors at micro- and macro-scales. Our findings suggest that macroclimate is a poor predictor of NPP, thereby indicating that microclimate is the main driver due to the strong effects of microtopographic factors on cryptogams. Metabolic activity is also crucial for estimating the NPP, which is highly dependent on the type, distribution, and duration of the hydration sources available throughout the year. Under RCP 4.5 and RCP 8.5, metabolic activity will increase slightly compared with that at present due to the increased precipitation events predicted in MIROC5. Temperature is highlighted as the main driver for NPP projections, and thus climate warming will lead to an average increase in NPP of 167–171% at the end of the century. However, small changes in other drivers such as light and relative humidity may strongly modify the metabolic activity patterns of poikilohydric autotrophs, and thus their NPP. Species with similar physiological response ranges to the species investigated in the present study are expected to behave in a similar manner provided that liquid water is available.

HIF3A Inhibition Triggers Browning of White Adipocytes via Metabolic Rewiring.

Maintenance of energy balance between intake and expenditure is a prerequisite of human health, disrupted in severe metabolic diseases, such as obesity and type 2 diabetes (T2D), mainly due to accumulation of white adipose tissue (WAT). WAT undergoes a morphological and energetic remodelling toward brown adipose tissue (BAT) and the BAT activation has anti-obesity potential. The mechanisms or the regulatory factors able to activate BAT thermogenesis have been only partially deciphered. Identifying novel regulators of BAT induction is a question of great importance for fighting obesity and T2D. Here, we evaluated the role of Hif3α in murine pre-adipocyte 3T3-L1 cell line, a versatile and well characterized biological model of adipogenesis, by gain- and loss-of function approaches and in thermogenesis-induced model in vivo. HIF3A is regulated by inflammation, it modulates lypolysis in adipose tissue of obese adults, but its role in energy metabolism has not previously been investigated. We characterized gene and protein expression patterns of adipogenesis and metabolic activity in vitro and mechanistically in vivo. Overexpression of Hif3α in differentiating adipocytes increases white fat cells, whereas silencing of Hif3α promotes “browning” of white cells, activating thermogenesis through upregulation of Ucp1, Elovl3, Prdm16, Dio2 and Ppargc1a genes. Investigating cell metabolism, Seahorse Real-Time Cell Metabolism Analysis showed that silencing of Hif3α resulted in a significant increase of mitochondrial uncoupling with a concomitant increase in acetyl-CoA metabolism and Sirt1 and Sirt3 expression. The causal Hif3α/Ucp1 inverse relation has been validated in Cannabinoid receptor 1 (CB1) knockout, a thermogenesis-induced model in vivo. Our data indicate that Hif3α inhibition triggers “browning” of white adipocytes activating the beneficial thermogenesis rewiring energy metabolism in vitro and in vivo. HIF3A is a novel player that controls the energy metabolism with potential applications in developing therapy to fight metabolic disorders, as obesity, T2D and ultimately cancer.

Identification of an integrated stress and growth response signaling switch that directs vertebrate intestinal regeneration

BackgroundSnakes exhibit extreme intestinal regeneration following months-long fasts that involves unparalleled increases in metabolism, function, and tissue growth, but the specific molecular control of this process is unknown. Understanding the mechanisms that coordinate these regenerative phenotypes provides valuable opportunities to understand critical pathways that may control vertebrate regeneration and novel perspectives on vertebrate regenerative capacities.ResultsHere, we integrate a comprehensive set of phenotypic, transcriptomic, proteomic, and phosphoproteomic data from boa constrictors to identify the mechanisms that orchestrate shifts in metabolism, nutrient uptake, and cellular stress to direct phases of the regenerative response. We identify specific temporal patterns of metabolic, stress response, and growth pathway activation that direct regeneration and provide evidence for multiple key central regulatory molecules kinases that integrate these signals, including major conserved pathways like mTOR signaling and the unfolded protein response.ConclusionCollectively, our results identify a novel switch-like role of stress responses in intestinal regeneration that forms a primary regulatory hub facilitating organ regeneration and could point to potential pathways to understand regenerative capacity in vertebrates.

Novel localizations of TRPC5 channels suggest novel and unexplored roles: A study in the chick embryo brain.

Mammalian TRPC5 channels are predominantly expressed in the brain, where they increase intracellular Ca2+ and induce depolarization. Because they augment presynaptic vesicle release, cause persistent neural activity, and show constitutive activity, TRPC5s could play a functional role in late developmental brain events. We used immunohistochemistry to examine TRPC5 in the chick embryo brain between 8 and 20 days of incubation, and provide the first detailed description of their distribution in birds and in the whole brain of any animal species. Stained areas substantially increased between E8 and E16, and staining intensity in many areas peaked at E16, a time when chick brains first show organized patterns of whole-brain metabolic activation like what is seen consistently after hatching. Areas showing cell soma staining match areas showing Trpc5 mRNA or protein in adult rodents (cerebral cortex, hippocampus, amygdala, cerebellar Purkinje cells). Chick embryos show protein staining in the optic tectum, cerebellar nuclei, and several brainstem nuclei; equivalent areas in the Allen Institute mouse maps express Trpc5 mRNA. The strongest cell soma staining was found in a dorsal hypothalamic area (matching a group of parvicellular arginine vasotocin neurons and a pallial amygdalohypothalamic cell corridor) and the vagal motor complex. Purkinje cells showed strong dendritic staining at E20. Unexpectedly, we also describe neurite staining in the septum, several hypothalamic nuclei, and a paramedian raphe area; the strongest neurite staining was in the median eminence. These novel localizations suggest new unexplored TRPC5 functions, and possible roles in late embryonic brain development.

Spatially resolved correlative microscopy and microbial identification reveal dynamic depth- and mineral-dependent anabolic activity in salt marsh sediment.

SummaryCoastal salt marshes are key sites of biogeochemical cycling and ideal systems in which to investigate the community structure of complex microbial communities. Here, we clarify structural–functional relationships among microorganisms and their mineralogical environment, revealing previously undescribed metabolic activity patterns and precise spatial arrangements within salt marsh sediment. Following 3.7‐day in situ incubations with a non‐canonical amino acid that was incorporated into new biomass, samples were resin‐embedded and analysed by correlative fluorescence and electron microscopy to map the microscale arrangements of anabolically active and inactive organisms alongside mineral grains. Parallel sediment samples were examined by fluorescence‐activated cell sorting and 16S rRNA gene sequencing to link anabolic activity to taxonomic identity. Both approaches demonstrated a rapid decline in the proportion of anabolically active cells with depth into salt marsh sediment, from ~60% in the top centimetre to 9.4%–22.4% between 2 and 10 cm. From the top to the bottom, the most prominent active community members shifted from sulfur cycling phototrophic consortia, to putative sulfate‐reducing bacteria likely oxidizing organic compounds, to fermentative lineages. Correlative microscopy revealed more abundant (and more anabolically active) organisms around non‐quartz minerals including rutile, orthoclase and plagioclase. Microbe–mineral relationships appear to be dynamic and context‐dependent arbiters of biogeochemical cycling.

Hydrological, physicochemical and metabolic signatures in groundwater and snowmelt streams in the Japanese Alps

The unique hydrology and physicochemistry of alpine streams provide an important influence on the structure and function of inhabiting biological communities. A substantial body of research exists on alpine streams across many regions of the globe (e.g. Europe, North and South America and Greenland). To date, however, there have been few studies investigating the environmental conditions present in alpine streams across the Japanese archipelago. The lack of information on alpine streams in Japan is problematic as unique regional climates, e.g. some of the highest levels of snowfall globally, are likely to have repercussions for morphological, hydrological, physicochemical and metabolic signatures, causing them to differ from those observed in other regions. In this study we compare the morphology, hydrology, physicochemistry and metabolic activity of snowmelt and groundwater fed streams in the Kamikochi region of the Japanese Alps. Stream discharge, water chemistry (major ions, silica, dissolved oxygen), water temperature and channel stability were measured over a period of 16 months in 2017–2018. Metabolic activity was determined using Resazurin-Resorufin (Raz-Rru) Smart Tracer and variation in the Raz transformation rate was assessed to understand the effects of hydrology and physicochemistry on ecosystem functioning. Snowmelt streams were characterised by higher variability of water temperature, water chemistry and stream discharge, both, within and between sites. Indeed, two of the snowmelt streams experienced no flow conditions for several periods and also floods. In comparison, water chemistry, water temperature and stream discharge in groundwater fed streams were more temporally stable. Metabolic activity was higher in one groundwater fed stream, attributed to significant growth of macrophytes. These findings indicate that the patterns of morphology, hydrology, physicochemistry and metabolic activity across streams in the Japanese Alps largely resemble those identified elsewhere, although there were higher levels of inter-stream variation. The diversity and inter-site variation of hydrological and physicochemical conditions are likely responsible for the unique flora and fauna in the streams. This study therefore indicates the potential importance of habitat templates for the aquatic biodiversity hotspot in this region.

Sex-dimorphic Rostro-caudal Patterns of 5'-AMP-activated Protein Kinase Activation and Glucoregulatory Transmitter Marker Protein Expression in the Ventrolateral Ventromedial Hypothalamic Nucleus (VMNvl) in Hypoglycemic Male and Female Rats: Impact of Estradiol.

The ventromedial hypothalamic nucleus-ventrolateral part (VMNvl) is an estradiol-sensitive structure that controls sex-specific behavior. Electrical reactivity of VMNvl neurons to hypoglycemia infers that cellular energy stability is monitored there. Current research investigated the hypothesis that estradiol elicits sex-dimorphic patterns of VMNvl metabolic sensor activation and gluco-regulatory neurotransmission during hypoglycemia. Rostral-, middle-, and caudal-VMNvl tissue was separately micropunch-dissected from letrozole (Lz)- or vehicle-injected male and estradiol- or vehicle-implanted ovariectomized (OVX) female rats for Western blot analysis of total and phosphorylated5'-AMP-activated protein kinase (AMPK) protein expression and gluco-stimulatory [neuronal nitric oxide synthase (nNOS); steroidogenic factor-1 (SF1) or -inhibitory (glutamate decarboxylase65/67 (GAD)] transmitter marker proteins after sc insulin (INS) or vehicle injection. In both sexes, hypoglycemic up-regulation of phosphoAMPK was estradiol-dependent in rostral and middle, but not caudal VMNvl. AMPK activity remained elevated after recovery from hypoglycemia over the rostro-caudal VMNvl in female, but only in the rostral segment in male. In each sex, hypoglycemia correspondingly augmented or suppressed nNOS profiles in rostral and middle versus caudal VMNvl; these segmental responses persisted longer in female. Rostral and middle segmentSF1 protein was inhibited by estradiol-independent mechanisms in hypoglycemic males, but increased by estradiol-reliant mechanisms in female. After INS injection, GAD expression was inhibited in the male rostral VMNvl without estradiol involvement, but this hormone was required for broadersuppression of this profile in the female. Neuroanatomical variability of VMNvl metabolic transmitter reactivity to hypoglycemia underscores the existence of functionally different subgroups in that structure. The regional distribution and estradiol sensitivity of hypoglycemia-sensitive VMNvl neurons of each neurochemical phenotype evidently vary between sexes.

Biological Cell Investigation of Structured Nitinol Surfaces for the Functionalization of Implants.

Expandable implants including shape memory alloy (SMA) elements have great potential to minimize the risk of implant loosening and to increase the primary stability of bone anchoring. Surface structuring of such elements may further improve these properties and support osteointegration and bone healing. In this given study, SMA sheets were processed by deploying additive and removal manufacturing technologies for 3D-printed surgical implants. The additive technology was realized by applying a new laser beam melting technology to print titanium structures on the SMA sheets. The removal step was realized as a standard process with an ultrashort-pulse laser. The morphology, metabolic activity, and mineralization patterns of human bone marrow stromal cells were examined to evaluate the biocompatibility of the new surface structures. It was shown that both surface structures support cell adhesion and the formation of a cytoskeleton. The examination of the metabolic activity of the marrow stromal cells on the samples showed that the number of cells on the laser-structured samples was lower when compared to the 3D-printed ones. The calcium phosphate accumulation, which was used to examine the mineralization of marrow stromal cells, was higher in the laser-structured samples than in the 3D-printed ones. These results indicate that the additive- and laser-structured SAM sheets seem biocompatible and that the macrostructure surface and manufacturing technology may have positive influences on the behavior of the bone formation. The use of the new additive technique and the resulting macrostructures seems to be a promising approach to combine increased anchorage stability with simultaneously enhanced osteointegration.

0769 FDG-PET Imaging In Narcolepsy Type 1, Idiopathic Hypersomnia, And Non-Sleepy Controls

Abstract Introduction Functional imaging of narcolepsy type 1 (NT1) has shown disparate results, with evidence for both regional hyper- and hypo-metabolism. A FDG-PET study of idiopathic hypersomnia (IH) demonstrated regional hypermetabolism within the salience network. Methods Patients with NT1 (n=14) or IH (n=16) were recruited, with age-matched, non-sleepy controls (HC, n=8). Patients discontinued treatment for ≥5 half-lives. Participants underwent injection of 18F-fludeoxyglucose (FDG) in a dimly-lit room and were asked to remain awake, seated quietly. Simultaneous 6-channel EEG, EOG, and EMG were collected. Participants were alerted by a loud noise if sleep onset was observed. Thirty minutes after injection, patients underwent 36-minute PET scan. Images were spatially normalized to MPRAGE images and analyzed for group differences using SPM8. Results Groups were similar in age (NT1: 30.0 (+/-SD 8.3), IH: 36.3 (+/-12.4), HC: 33.2 (+/-16.2), p=0.29) and gender (%women, NT1: 71%, IH: 87.5%, HC: 62.5%, p=0.37). Patients were sleepier than controls by Epworth (NT1: 18.2 (+/-3.5), IH: 15.8 (+/-3.2), HC: 5.0 (+/-2.7), p<0.0001) and MSLT mean latency (NT1: 2.0 (+/-1.4), IH: 5.1 (+/-1.7), HC: 14.6 (+/-2.6), p<0.0001). Despite attempts to remain awake, NT1 patients had difficulty maintaining wakefulness during uptake, obtaining 6.2 (+/-5.9) minutes sleep versus <1 minute for the other groups. Compared to controls, NT1 patients demonstrated increased activation in bilateral precentral gyri, left postcentral gyrus, left middle frontal gyrus, right insula, right inferior and superior temporal gyri, right fusiform gyrus, and bilateral inferior frontal gyri. Compared to controls, IH patients demonstrated increased activation in bilateral precuneus, bilateral inferior and middle frontal gyri, left middle and superior temporal gyri, left inferior parietal lobule, and left anterior cingulate. Conclusion Different patterns of metabolic activity are seen in two hypersomnia disorders, implying disease-specific activity rather than non-specific sleepiness. Inadvertent sleep during uptake is more common in NT1. Support K23 NS083748

Modeling the coupled dynamics of stream metabolism and microbial biomass

AbstractEstimating and interpreting ecosystem metabolism remains an important challenge in stream ecology. Here, we propose a novel approach to model, estimate, and predict multiseasonal patterns of stream metabolism (gross primary production [GPP] and ecosystem respiration [ER]) at the reach scale leveraging on increasingly available long‐term, high‐frequency measurements of dissolved oxygen (DO). The model uses DO measurements to estimate the parameters of a simple ecosystem model describing the underlying dynamics of stream autotrophic and heterotrophic microbial biomass. The model has been applied to four reaches within the Ybbs river network, Austria. Even if microbial biomasses are not observed, that is, they are treated as latent variables, results show that by accounting for the temporal dynamics of biomass, the model reproduces variability in metabolic fluxes that is not explained by fluctuations of light, temperature, and resources. The model is particularly data‐demanding: to estimate the 11 parameters used in this formulation, it requires sufficiently long, for example, annual, time series, and significant scouring events. On the other hand, the approach has the potential to separate ER into its autotrophic and heterotrophic components, estimate a richer set of ecosystem carbon fluxes (i.e., carbon uptake, loss, and scouring), extrapolate metabolism estimates for periods when DO measurements are unavailable, and predict how ecosystem metabolism would respond to variations of the driving forces. The model is seen as a building block to develop tools to fully appreciate multiseasonal patterns of metabolic activity in river networks and to provide reliable estimations of carbon fluxes from land to ocean.

Using metabolic information for categorization and read-across in the OECD QSAR Toolbox

Metabolism is a critical aspect of toxicokinetics. It is crucial to take it into account when evaluating similarity among the chemicals participating in a read-across prediction. Lack of considerations on metabolism represents a major source of uncertainty in a read-across justification. To better assist users in applying metabolic considerations during data gap filling, the metabolism/transformations functionality in the OECD QSAR Toolbox has been upgraded in version 4. Analyses of metabolic similarity are specific to a toxic endpoint and dependent on data availability. By using optimized features, the metabolic simulators available in Toolbox can predict the generation of possible metabolites and take them into account for read-across. In the traditional downstream approach, metabolic information in the Toolbox is used to identify the formation of (a)biotic products of known toxicity and read-across their toxicity to the parent chemical. By a stepwise protocol the user may explore knowledge embedded in the Toolbox to identify source analogues that have the same pattern of metabolic activation as the target. Furthermore, following the upstream approach, precursors of the chemicals could be also searched in the Toolbox databases. Five scenarios, highlighting the applications of the metabolism in chemical assessment within the Toolbox, are illustrated.

Spatial and temporal studies of metabolic activity: contrasting biochemical kinetics in tissues and pathways during fasted and fed states.

The regulation of nutrient homeostasis, i.e., the ability to transition between fasted and fed states, is fundamental in maintaining health. Since food is typically consumed over limited (anabolic) periods, dietary components must be processed and stored to counterbalance the catabolic stress that occurs between meals. Herein, we contrast tissue- and pathway-specific metabolic activity in fasted and fed states. We demonstrate that knowledge of biochemical kinetics that is obtained from opposite ends of the energetic spectrum can allow mechanism-based differentiation of healthy and disease phenotypes. Rat models of type 1 and type 2 diabetes serve as case studies for probing spatial and temporal patterns of metabolic activity via [2H]water labeling. Experimental designs that capture integrative whole body metabolism, including meal-induced substrate partitioning, can support an array of research surrounding metabolic disease; the relative simplicity of the approach that is discussed here should enable routine applications in preclinical models.

The phase of the estrous cycle modifies the endocrine, metabolic and behavior rhythms in ewes

The aim of this study was to compare circadian rhythms of serum cortisol and insulin concentrations, glycemia, glycemia:insulin ratio (GLY:INS), rectal, vaginal and surface (ST) temperatures as well behavioral patterns during the follicular (FOL) and luteal (LUT) phases in ewes. All the variables were measured during both phases of the estrous cycle in 8 West African ewes during a 24 h period. Cortisol concentrations were greater during FOL than LUT (30.9 ± 2.1 ng mL−1 vs 24.1 ± 2.1 ng mL−1; P < 0.01); cosinor analysis revealed also differences in the circadian pattern: while the acrophase of the cortisol secretion during the FOL occurred at 10:00 ± 0:49 h, coinciding with higher environmental temperatures during the LUT was observed at 05:07 ± 0:49 h (P < 0.05). There were no differences in insulin concentrations according to the phase of the estrous cycle (FOL: 43.3 ± 6.6 μg mL−1 vs LUT: 44.9 ± 6.6 μg mL−1); however, insulin secretion varied according to the time of the day (P < 0.01) and showed a strong robustness in both phases of the estrous cycle (>40%), with acrophase occurring at sunset. Glycemia was greater during the FOL than the LUT (69.9 ± 1.1 mg dL−1 vs 63.9 ± 1.1 mg dL−1, respectively; P < 0.01), and varied according to the time of the day (P < 0.05), without interaction between both effects. However, the strength of rhythmicity was <40% during both phases. GLY:INS ratio was greater in FOL than LUT (2.2 ± 0.2 vs 1.8 ± 0.2, respectively; P = 0.04), indicating that the greater glycemia observed during FOL did not trigger the same secretion of INS than during LUT. Rectal and vaginal temperatures, as well as nasal vein, front and neck ST were greater during FOL than during LUT (P < 0.05). There was no circadian rhythm for vaginal temperature but, both rectal temperature and the mean surface temperature showed a strong robustness (>65%). The mesor of the rectal temperature was greater during the FOL than during the LUT (39.2 ± 0.1 °C vs 38.8 ± 0.1 °C, respectively; P < 0.05). Ewes were observed urinating more times during the FOL than during the LUT (7.3 ± 1.5% vs 1.7 ± 1.5%, respectively, P < 0.05). Ewes were observed standing, drinking water and in bipedal position more times during FOL than during the LUT (P = 0.07, P = 0.08 and P = 0.07, respectively). In conclusion, the phase of the estrous cycle affected the secretion and the circadian rhythm of cortisol and in consequence the metabolic activity, thermoregulatory response and behavior pattern in ewes.