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A carnitine transporter at the blood–brain barrier modulates sleep via glial lipid metabolism in <i>Drosophila</i>
To regulate brain function, peripheral compounds must traverse the blood–brain barrier (BBB), an interface between the brain and the circulatory system. To determine whether specific transport mechanisms are relevant for sleep, we conducted a BBB-specific inducible RNAi knockdown (iKD) screen for genes affecting sleep in Drosophila . We observed reduced sleep with knockdown of solute carrier CG6126 , a carnitine transporter, as determined by isotope flux. Our findings suggest that CG6126 regulation of sleep is through the role of the carnitine shuttle in regulating fatty acid metabolism as lipid droplets accumulate in the brains of CG6126 BBB iKD flies. Knocking down mitochondrial carnitine transferases in non-BBB glial cells mimicked the reduced sleep of the CG6126 BBB iKD flies, while bypassing the necessity of carnitine transport with dietary medium-chain fatty acids or palmitoylcarnitine rescued sleep. We propose that carnitine transport via CG6126 promotes brain fatty acid metabolism necessary for maintaining sleep.
The international trial of nasal oxygen therapy after cardiac surgery (NOTACS) in patients at high risk of postoperative pulmonary complications: Economic evaluation protocol and analysis plan
Introduction High-Flow Nasal Therapy (HFNT) is an innovative non-invasive form of respiratory support. Compared to standard oxygen therapy (SOT), there is an equipoise regarding the effect of HFNT on patient-centred outcomes among those at high risk of developing postoperative pulmonary complications after undergoing cardiac surgery. The NOTACS trial aims to determine the clinical and cost-effectiveness of HFNT compared to SOT within 90 days of surgery in the United Kingdom, Australia, and New Zealand. This protocol describes the methods and analyses planned for economic evaluation embedded within the ongoing NOTACS trial. Methods and analysis The economic evaluation will identify, measure and value resources and health outcomes in both trial arms and compare changes in costs with ‘days alive and at home’ and EQ-5D-5L quality adjusted life years (QALYs) from the perspective most relevant to the decision-making country. Results from pooling data across the trial will use health and social care sector perspective. All patient-specific data including hospital/community care and health outcomes will be collected prospectively. Unit costs will be sourced from national, published or local data. Missing data will be assessed, with values replaced depending on assumed mechanism of missingness, and impact of replacement on cost-effectiveness assessed. Costs and outcomes by trial arm will be presented as components and totals per patient using a range of descriptive statistics. Regression models for costs and effects will account for patient characteristics, quality of life and health service utilization at baseline. Uncertainty in parameters, sampling and heterogeneity will be addressed through deterministic, probabilistic and subgroup analyses to assess the impact of varying methods and assumptions for costs, outcomes and approaches used in base-case analysis. Results will be interpreted using recommended national cost-effectiveness thresholds. Registration details The study is registered with ISRCTN (ISRCTN14092678) on 13/05/2020. ISRCTN is a primary registry of the WHO ICTRP network and includes all items from the WHO Trial Registration data set.
Investigation of (mis-)orientation in zincblende GaN grown on micro-patterned Si(001) using electron backscatter diffraction
We present the application of electron backscatter diffraction (EBSD) as a technique for characterizing wurtzite (wz) and zincblende (zb) polytypes of GaN grown upon micropatterned Si (001) substrates. The Si substrate is etched to create parallel V-shaped grooves with opposing {111} facets before the deposition of GaN. EBSD revealed that wz-GaN growth fronts initially form on the {111} Si facets before undergoing a transition from a wurtzite to zincblende structure as the two growth fronts meet. Orientation analysis of the GaN structures revealed that the wz-GaN growth fronts had different growth orientations but shared the same crystallographic relationship with the zb-GaN such that ⊥{303¯8}wz∥⟨110⟩zb, ⟨112¯0⟩wz∥⟨110⟩zb, and ⊥{303¯4}wz∥⟨001⟩zb. Furthermore, the crystallographic relationship, {0001}wz-GaN∥{111}zb-GaN∥{111}Si, and alignment of the wz- and zb-GaN with respect to the Si substrate was investigated. The two wz-GaN ⟨0001⟩ growth directions were expected to coalesce at an angle of 109.5°; however, measurements revealed an angle of 108°. The resultant misalignment of 1.5° induces misorientation in the zb-GaN crystal lattice. While the degree of misorientation within the zb-GaN lattice is low, &lt;1°, the zb-GaN lattice is deformed and bends toward the wz-GaN interfaces about the specimen direction parallel to the length of the V-groove. Further EBSD measurements over larger areas of the sample revealed that these results were consistent across the sample. However, it was also revealed that additional factors induce changes in the orientation of the zb-GaN lattice, which may relate to the initial growth conditions of the zb-GaN.
Behavioral nudges prevent loan delinquencies at scale: A 13-million-person field experiment
Americans collectively hold over $1.6 trillion in student loan debt, and over the last decade millions of borrowers have defaulted on loans, with serious consequences for their financial health. In a 13-million-person field experiment with the U.S. Department of Education, we tested the effectiveness of different email interventions to inform borrowers about alternative repayment options after a missed loan payment. Our interventions tested whether sending monthly behaviorally-informed emails, providing follow-up reminders, framing benefits in percentage (vs. dollar) terms, and providing just one recommended action step at a time (vs. two) affected borrower outcomes. We find that i) behaviorally-informed emails reduce estimated 60-d delinquencies by 0.42 pp, ii) reminders boost the efficacy of such emails by 0.57 pp, iii) describing potential savings in percentage terms is more effective than describing these benefits in dollar terms, reducing estimated delinquencies by 0.14 pp, and iv) encouraging two actions (i.e., enrollment in income-driven repayment plans and auto debit programs) repeatedly across two emails is marginally more effective than encouraging one action at-a-time across two emails, reducing estimated delinquencies by 0.05 pp. Overall, if scaled to all 13-million borrowers in our experiment, we estimate that our best-performing intervention would have averted approximately 79,800 60-d delinquencies. Our findings i) highlight the benefits of describing potential savings in percentage terms, which may magnify perceived savings for recipients, ii) underscore the risks of oversimplification, and iii) demonstrate that nudges can be an effective, low-cost complement to other policies for reducing delinquencies and supporting borrowers with student loan debt.
Smart home technology to support engagement in everyday activities while ageing: A focus group study with current and future generations of older adults
Despite the potential of smart home technologies (SHT) to support everyday activities, the implementation rate of such technology in the homes of older adults remains low. The overall aim of this study was to explore factors involved in the decision-making process in adopting SHT among current and future generations of older adults. We also aimed to identify and understand barriers and facilitators that can better support older adults’ engagement in everyday activities. Focus group discussions were used to explore the perspectives of people from diverse age groups (30–39, 50–59, and 70-79-year-olds). Three focus groups met twice at a lab designed as a two-room home equipped with SHT. Our findings revealed that the participants’ decision-making process for adopting SHT involved designs that must be adapted to the changing physical abilities and diverse needs of users. Some conditions, such as ideas for re-invention, were identified after the integration of SHT. Concerns about reliability, complicated interfaces, and value to the user influenced the decision to adopt SHT, highlighting the importance of these factors for successful implementation. Some participants did not fully understand what SHT is nor perceive its benefits, but they expressed a desire to acquire the skills and knowledge to operate SHT. Furthermore, participants desired SHT that can support an active lifestyle. The perceived advantages of SHT include enhancing the sense of security and safety, which can facilitate engagement in everyday activity. Some participants experienced a positive impact on quality of life, related to comfortable living with the implementation of SHT. Adults across age groups perceive that SHT can enhance engagement in everyday activity and the sense of safety and security. However, it is essential to identify solutions for better usability. More collaborative efforts involving diverse stakeholders are vital to bridge the disconnect between SHT design and users’ needs and preferences.
Leaky-integrate-fire and reconfigurable neuron spiking in a field free spin Hall nano-oscillator with a conically magnetized free layer
Spintronic oscillators being highly nonlinear have gained immense attention to mimic the neuron spiking behavior in spiking neural networks used for building neuromorphic computing hardware. However, the need for an external magnetic field to realize spintronic oscillators imposes significant limitations on their scalability, tunability, and fabrication complexity. So, in this study, we have realized a bias-field-free spin Hall nano-oscillator (SHNO) using a heavy metal/magnetic tunnel junction (MTJ) heterostructure. The field-free operation is achieved by biasing the free layer of the MTJ into an easy cone regime. This regime arises when the first-order magnetic anisotropy field and the demagnetization field are balanced, and the influence of the second-order magnetic anisotropy becomes predominant. We have explored the oscillation properties of this field-free SHNO, focusing on frequency tunability with current and the output power spectral density through the macrospin and micromagnetic simulations. We have theoretically derived the critical current necessary for the onset of oscillations. Using this field-free SHNO, we demonstrated neuron-like spiking behavior analogous to the Hodgkin–Huxley model by applying a constant DC current. The tunability of spiking frequency in response to input current was also examined. Moreover, we showcased leaky-integrate-and-fire neuron spiking behavior by applying a pulsed current and the reconfigurable nature of neuron spiking under a time-varying ramp current. These spiking behaviors underline the potential applications of this device in the practical realization of brain-inspired neuromorphic computing with the spiking neural network.
Spreading dynamics of information on online social networks
Social media is profoundly changing our society with its unprecedented spreading power. Due to the complexity of human behaviors and the diversity of massive messages, the information-spreading dynamics are complicated, and the reported mechanisms are different and even controversial. Based on data from mainstream social media platforms, including WeChat, Weibo, and Twitter, cumulatively encompassing a total of 7.45 billion users, we uncover a ubiquitous mechanism that the information-spreading dynamics are basically driven by the interplay of social reinforcement and social weakening effects. Accordingly, we propose a concise equation, which, surprisingly, can well describe all the empirical large-scale spreading trajectories. Our theory resolves a number of controversial claims and satisfactorily explains many phenomena previously observed. It also reveals that the highly clustered nature of social networks can lead to rapid and high-frequency information bursts with relatively small coverage per burst. This vital feature enables social media to have a high capacity and diversity for information dissemination, beneficial for its ecological development.
Identification of diabetic retinopathy lesions in fundus images by integrating CNN and vision mamba models
Diabetic retinopathy, a retinal disorder resulting from diabetes mellitus, is a prominent cause of visual degradation and loss among the global population. Therefore, the identification and classification of diabetic retinopathy are of utmost importance in the clinical diagnosis and therapy. Currently, these duties are extensively carried out by manual examination utilizing the human visual system. Nevertheless, manual examination is sometimes arduous, time-consuming, and prone to errors. Deep learning-based methods have recently demonstrated encouraging results in several areas, such as image categorization and natural language mining. The majority of deep learning techniques developed for medical image analysis rely on convolutional modules to extract the inherent structure of images within a certain local receptive field. Furthermore, transformer-based models have been utilized to tackle medical image processing problems by capitalizing on global connections among distant pixels in the images. Considering these analyses, this work presents a comprehensive deep learning model that combines convolutional neural network and vision mamba models. This model is designed to accurately identify and classify diabetic retinopathy lesions displayed in fundus images. Furthermore, the vision mamba component incorporates the bidirectional state space method and positional embedding to enable the location sensitivity of visual data samples and meet the conditions for global relationship context. An evaluation of the suggested method was carried out by comparison experiments between state-of-the-art algorithms and the proposed methodology. Empirical findings demonstrate that the suggested methodology surpasses the most advanced algorithms on the datasets that are accessible openly. Hence, the suggested approach may be regarded as a helpful tool for therapeutic processes.
Deformation and reverse phase transformation mechanism of high-pressure HCP iron during unloading process
Iron will undergo the BCC to HCP transformation under pressure, but the reverse process during the unloading path has not been fully revealed on the atomic scale. This work investigated the unloading dynamics of a HCP single crystal of iron, focusing on the microstructure evolution and related mechanical characteristics. For unloading along the normal direction of the (1¯21¯0) and (101¯0) planes, a mechanism for coupling between twinning and phase transformation was reported. The HCP to BCC transformation with the rod-like structure and twinning was revealed, which was well supported by previous experiments. For unloading along the normal direction of the (0001) plane, the HCP–FCC–BCC transition was observed. Significant shear stress was generated internally, leading to significant dislocations. There are multiple transition paths of the HCP to FCC phase, resulting in the formation of grain boundaries and ultimately leaving the polycrystalline structures. This process was accompanied by coupled development of dislocations, grain mergers, and phase transitions. As the unloading process gradually evolves into the stretching process, detwinning and reconstruction will occur for unloading along the normal direction of the (1¯21¯0) and (101¯0) planes, accompanied by grain rotation.
Light signal regulates endoreduplication and tomato fruit expansion through the SlPIF1a-SlTLFP8-SlCDKB2 module
Light serves as an energy source for cell division and expansion during fruit development. Cell expansion significantly influences fruit size and is closely linked to endoreduplication, a unique cell cycle variation characterized by DNA replication without cytokinesis. Paradoxically, under conditions of ample photosynthates, light signaling suppresses cell expansion. The intricate regulation of endoreduplication in response to light signaling during fruit development has remained an intriguing question. Here, our study revealed that Tubby-like F-box protein 8 (SlTLFP8) orchestrated endoreduplication to facilitate fruit cell expansion. As an Skp1-Cullin-F-box (SCF)-type E3 ligase, SlTLFP8 promoted the ubiquitination and subsequent degradation of CYCLIN-DEPENDENT KINASE B2 (SlCDKB2), thereby elevating DNA ploidy. The light signaling component PHYTOCHROME-INTERACTING FACTOR 1a (SlPIF1a), identified as a pivotal negative regulator in the plant’s light response, was found to directly interact with the promoter of the SlTLFP8 gene, thereby stimulating its transcriptional activation. Indeed, SlPIF1a contributed to a faster expansion rate of tomato fruit during nighttime. Altogether, our results elucidate the connection between light signals and fruit size regulation through endoreduplication.
Beyond the jab: Unravelling the complexities of vaccine adoption for East Coast Fever in rural Kenya
East Coast Fever (ECF) is one of the leading causes of livestock mortality and reduced productivity across Eastern Africa, and while a live vaccine against it known as the Infection and Treatment Method has existed for three decades now, its adoption by affected communities remains low. This study sought to provide a detailed examination of the dynamics that shape Infection Treatment Method (ITM) vaccine adoption behaviours. The study examined individual, socio-cultural and ecological- level factors influencing ITM adoption using the socio-ecological model. Analyzing data obtained from 18 focus group discussions, 30 in-depth interviews with livestock keepers, and 25 key informant interviews conducted with community stakeholders, the study identified factors associated with vaccine adoption within pastoralist communities in rural Kenya. These factors included knowledge and awareness of the Infection Treatment Method vaccine, its cost, livestock keepers’ perceptions of East Coast fever relative to other livestock diseases, wildlife-livestock interactions, climate as contributing factors, and wildlife-livestock interactions influencing ECF risk and severity. Overall, the study findings emphasize the need for multifaceted strategies to increase vaccine adoption among livestock keepers.
Interfacial passivation of CdTe solar cells using Mg-doped SnO2 as electron transport layer for enhanced photovoltaic efficiency
Tin oxide (SnO2), known for its excellent optical and electronic properties, is increasingly favored as an electron transport layer(ETL) in high-efficiency thin film solar cells. However, its direct use in SnO2/CdTe heterojunction solar cells results in relatively low open-circuit voltage (VOC) and inferior power conversion efficiency (PCE). Herein, we achieve significantly high efficiency in CdTe-based photovoltaic devices by using Mg-doped SnO2 as ETLs, fabricated through magnetron co-sputtering technique. Capacitance–voltage (C–V) and space-charge-limited current measurements reveal that Mg doping significantly enhances the built-in potential at the SnO2/CdTe interface and reduces trap density over twofold. First-principles calculations indicate that the trap states originating from the Sn atom dangling bonds at the interface can be effectively passivated by the formation of MgSn defects, which are facilitated by Mg-doped SnO2. The resulting improvements in VOC and PCE are further validated through device simulations. This study demonstrates the potential of SnO2 as an ETL in high-efficiency CdTe solar cells and highlights the effectiveness of doping engineering in the contact layer for improving the interfacial properties of semiconductor devices.
The perceptual primacy of feeling: Affectless visual machines explain a majority of variance in human visually evoked affect
Looking at the world often involves not just seeing things, but feeling things. Modern feedforward machine vision systems that learn to perceive the world in the absence of active physiology, deliberative thought, or any form of feedback that resembles human affective experience offer tools to demystify the relationship between seeing and feeling, and to assess how much of visually evoked affective experiences may be a straightforward function of representation learning over natural image statistics. In this work, we deploy a diverse sample of 180 state-of-the-art deep neural network models trained only on canonical computer vision tasks to predict human ratings of arousal, valence, and beauty for images from multiple categories (objects, faces, landscapes, art) across two datasets. Importantly, we use the features of these models without additional learning, linearly decoding human affective responses from network activity in much the same way neuroscientists decode information from neural recordings. Aggregate analysis across our survey, demonstrates that predictions from purely perceptual models explain a majority of the explainable variance in average ratings of arousal, valence, and beauty alike. Finer-grained analysis within our survey (e.g. comparisons between shallower and deeper layers, or between randomly initialized, category-supervised, and self-supervised models) point to rich, preconceptual abstraction (learned from diversity of visual experience) as a key driver of these predictions. Taken together, these results provide further computational evidence for an information-processing account of visually evoked affect linked directly to efficient representation learning over natural image statistics, and hint at a computational locus of affective and aesthetic valuation immediately proximate to perception.
Measurement of inferior colliculus volume based on MRI image stacks and its relationship with age and hearing status
The inferior colliculus is a key nucleus in the central auditory pathway, integrating acoustic stimuli from both cochleae and playing a crucial role in sound localization. It undergoes functional and structural development in childhood and experiences age-related degeneration later in life, contributing to the progression of age-related hearing loss. This study aims at finding out, whether the volume of the human inferior colliculus can be determined by analysis of routinely performed MRIs and whether there is any age-related variation. A further goal is to detect correlations between volume and existing hearing loss of the patients. A retrospective search in the data of the Regensburg ENT department was done. 123 MRI datasets were used to mark the voxels of the inferior colliculus on the MRI layers. The volumes could then be calculated by using the respective DICOM data and were correlated with age, gender and hearing status of the patients. Results suggested that a voxel-based method on routine clinical MRI stacks to determine the volume of the inferior colliculus is possible. The volume shows an age-dependency. There is a growth from infancy until adulthood and a significant decrease in patients over the age of 60 years. Left and right inferior colliculi do not show any systematic asymmetry in volume. There is no difference between females and males. In the group with asymmetric hearing (n = 13) a significant reduction of the volume on the deprived side (p = 0.036) was found. The proportion of subjects with severe hearing loss at least on one side was significantly higher in the old (>60 years) as compared to younger adults (10 to 60 years), suggesting that severe hearing loss may be associated with a reduced volume of the inferior colliculus in aged humans.
Enhanced blue emission and afterglow properties of Sr2MgSi2O7:Eu2+, Dy3+ phosphors for flexible transparent labels
Long afterglow is a fascinating luminescence phenomenon exhibited by certain storage phosphors that emit visible light after being stimulated by ultraviolet rays. Strontium magnesium silicate phosphors doped with europium and dysprosium (Sr2MgSi2O7:Eu2+, Dy3+) have garnered attention in recent years. Enhancing the afterglow performance of these phosphors remains a significant challenge. In this study, we investigate the enhancement of afterglow performance in Sr2MgSi2O7:Eu2+, Dy3+ phosphors prepared via a sol–gel auto-combustion method using commercial silica (CS) and lab-made nanosilica (NS). Our results reveal that the afterglow performance of the NS-based phosphor is significantly improved, glowing with optimal intensity for a prolonged period compared to the CS-based phosphor. Time-resolved photoluminescence studies show that the average lifetime of the NS-based phosphor is enhanced tenfold compared to the CS-based phosphor, attributed to the improved crystallinity of the NS-based phosphor. Photoluminescence studies indicate that both phosphors exhibit comparable performance. Thermoluminescence studies suggest that the presence of multiple trap levels with varying trap depths in the NS-based phosphor allows it to exhibit extended afterglow emission than the CS-based phosphor. Structural, morphological, and optical properties of the phosphors were analyzed using x-ray diffraction, Fourier transform infrared, x-ray photoelectron spectroscopy, field emission scanning electron microscopy, and UV–vis techniques. The underlying mechanism of the afterglow is explained in detail. The prepared phosphor was used to create flexible and transparent labels with silicone rubber, which can serve as indicators during dark hours.
Iron limitation triggers roseoceramide biosynthesis and membrane remodeling in marine roseobacter
Chemical communication between marine bacteria and their algal hosts drives population dynamics and ultimately determines the fate of major biogeochemical cycles in the ocean. To gain deeper insights into this small molecule exchange, we screened niche-specific metabolites as potential modulators of the secondary metabolome of the roseobacter, Roseovarius tolerans . Metabolomic analysis led to the identification of a group of cryptic lipids that we have termed roseoceramides. The roseoceramides are elicited by iron-binding algal flavonoids, which are produced by macroalgae that Roseovarius species associate with. Investigations into the mechanism of elicitation show that iron limitation in R. tolerans initiates a stress response that results in lowered oxidative phosphorylation, increased import and catabolism of algal exudates, and reconfiguration of lipid synthesis to prioritize production of roseoceramides over phospholipids, likely to fortify membrane integrity as well as promote a sessile and symbiotic lifestyle. Our findings add new small molecule words and their “meanings” to the algal-bacterial lexicon and have implications for the initiation of these interactions.
Development, validation, and reliability testing of the College Perspectives around Food Insecurity survey
The objective of this study was to develop and to test the validity and reliability of a survey aimed to evaluate internal and external factors associated with college food insecurity. Researchers used a mixed methods approach to evaluate the College Perspectives around Food Insecurity survey. Survey items were constructed from interview data and assigned a social cognitive theory concept (environment, personal, or behavior). Two rounds of expert reviews established content validity (Round 1, n = 3; Round 2, n = 2). Researchers evaluated face validity through two rounds of cognitive interviews with college students 18+ years old (Round 1, n = 9; Round 2, n = 16) and tested survey reliability (n = 105). Researchers used descriptive statistics, test-retest reliability statistics, and Cronbach’s alpha scores for data analysis. The initial survey contained 143 items. After feedback from expert reviewers and cognitive interviews, the final survey contained 99 items. Test-retest reliability was 0.99, and Cronbach’s alpha scores were 0.74 for environment, 0.47 for personal, and 0.39 for behavior. The College Perspectives around Food Insecurity survey can be used to better understand internal and external factors associated with food insecurity in college students, which can inform interventions aimed at assisting this population.
Robust hybrid perovskite self-rectifying memristor for brain-inspired computing and data storage
Conventional computing architectures are not suited to meet the unique workload requirements of artificial intelligence and deep learning, which has sparked a growing interest in memory-centric computing. One primary challenge in this field is sneak path current in memory devices, which degrades data storage and reliability. Another critical issue is ensuring device performance stability over time and under varying environmental conditions. To overcome these challenges, in this work, we introduce a Dion–Jacobson perovskite-based self-rectifying memory cell that not only reduces the sneak path current but also demonstrates remarkable stability in electrical parameters. The fabricated device maintains consistent performance, including rectification ratio (∼103), on/off ratio (∼103), and set voltage (∼0.52 V), for over 200+ days within a temperature range of 25–70 °C and relative humidity conditions up to 70%RH. Importantly, our work represents an innovative step forward in the observation of self-rectification and stable performance in perovskite-based devices, showing the way for their widespread application in memory-centric computing architectures. Furthermore, to understand the electrical behavior across its different states, i.e., high resistance state and low resistance state, electrochemical impedance spectroscopy is performed, which gives insight into the individual contribution of resistance, capacitance, and inductance.
Calcineurin governs baseline and homeostatic regulations of non–rapid eye movement sleep in mice
Sleep need accumulates during waking and dissipates during sleep to maintain sleep homeostasis (process S). Besides the regulation of daily (baseline) sleep amount, homeostatic sleep regulation commonly refers to the universal phenomenon that sleep deprivation (SD) causes an increase of sleep need, hence, the amount and intensity of subsequent recovery sleep. The central regulators and signaling pathways that govern the baseline and homeostatic sleep regulations in mammals remain unclear. Here, we report that enhanced activity of calcineurin Aα (CNAα)—a catalytic subunit of calcineurin—in the mouse brain neurons sharply increases the amount (to ~17-h/d) and delta power—a measure of intensity—of non–rapid eye movement sleep (NREMS). Knockout of the regulatory ( CnB1 ) or catalytic ( CnAα and CnAβ ) subunits of calcineurin diminishes the amount (to ~4-h/d) and delta power of baseline NREMS, but also nearly abrogates the homeostatic recovery NREMS following SD. Accordingly, mathematical modeling of process S reveals an inability to accumulate sleep need during spontaneous or forced wakefulness in calcineurin deficient mice. Moreover, calcineurin promotes baseline NREMS by antagonizing wake-promoting protein kinase A and, in part, by activating sleep-promoting kinase SIK3. Together, these results indicate that calcineurin is an important regulator of sleep need and governs both baseline and homeostatic regulations of NREMS in mice.
Cross-species comparison of AlphaFold-derived G protein-coupled receptor structures reveals novel melatonin-related receptor in Neurospora crassa
Melatonin, a molecule with diverse biological functions, is ubiquitously present in living organisms. There is significant interest in understanding melatonin signal transduction pathways in humans, particularly due to its critical role in regulating the sleep-wake cycle. However, a knowledge gap remains in fully elucidating the mechanisms by which melatonin influences circadian regulation. To bridge this gap, there is a growing need for a model system to study the role of melatonin in circadian clocks, with Neurospora crassa being a promising candidate. As a first step in this investigation, we focused on identifying melatonin receptors in N. crassa. Given the lack of sequence similarity between potential receptors in this fungus and known human melatonin receptors, we utilized structural similarity analysis through AlphaFold2. This approach led to the identification of a strong candidate gene, gpr-3, which shares structural similarities with human melatonin receptors. Experimental validation confirmed that the removal of GPR-3 from cells results in the absence of melatonin signaling. This proof-of-concept study underscores the potential of N. crassa as a model organism for circadian research and demonstrates the broader applicability of using AlphaFold2, especially when sequence similarity does not lead to candidate genes, for identifying novel receptors across different species.