Miracle-dz/UniFAR-FTUs huggingface dataset:
Abundances, ecologies, and distributions of Rhagoletis Loew, 1862 (Diptera: Tephritidae) flies in central Washington State, U.S.A. inferred from fly trapping surveys

Abstract. Target and non-target Rhagoletis Loew, 1862 (Diptera: Tephritidae) flies trapped in surveys can provide new information on fly abundances, ecologies, and distributions. Here, data from surveys for native R. indifferens Curran, 1932 in non-commercial sweet cherry trees and non-native R. pomonella (Walsh, 1867) in non-commercial apple, crabapple, and hawthorn trees in central Washington State, U.S.A. were used to determine relative abundances of target and non-target Rhagoletis on traps and to test the hypotheses that fly abundances are site, tree type, and seasonal period dependent. Rhagoletis indifferens was the most abundant Rhagoletis in cherry trees. Non-native R. completa Cresson, 1929 was the most abundant Rhagoletis caught in R. pomonella host trees, with overall results suggesting it is the most numerous and/or dispersive Rhagoletis in central Washington. With support from the literature, we infer that: R. pomonella is less tolerant of arid central Washington summers than R. completa, native R. zephyria Snow, 1894, R. indifferens, and native R. basiola (Osten Sacken, 1877); Rhagoletis species diversity is lower in suburban than rural habitats due to the predominant host plants present; all fly species disperse annually at similar relative abundances, resulting in geographic range expansions over a few generations; and peak seasonal dispersal of flies to non-natal tree species coincides with natal host fruit development, resulting in colonization of new fruiting host patches. Differential fly tolerances of arid summer climates due to adaptation or preadaptation, habitat type, and annual and seasonal dispersal patterns could explain abundances and distributions of native and non-native Rhagoletis species in central Washington.
Fuzzing File Systems via Two-Dimensional Input Space Exploration

File systems, a basic building block of an OS, are too big and too complex to be bug free. Nevertheless, file systems rely on regular stress-testing tools and formal checkers to find bugs, which are limited due to the ever-increasing complexity of both file systems and OSes. Thus, fuzzing, proven to be an effective and a practical approach, becomes a preferable choice, as it does not need much knowledge about a target. However, three main challenges exist in fuzzing file systems: mutating a large image blob that degrades overall performance, generating image-dependent file operations, and reproducing found bugs, which is difficult for existing OS fuzzers. Hence, we present JANUS, the first feedback-driven fuzzer that explores the two-dimensional input space of a file system, i.e., mutating metadata on a large image, while emitting image-directed file operations. In addition, JANUS relies on a library OS rather than on traditional VMs for fuzzing, which enables JANUS to load a fresh copy of the OS, thereby leading to better reproducibility of bugs. We evaluate JANUS on eight file systems and found 90 bugs in the upstream Linux kernel, 62 of which have been acknowledged. Forty-three bugs have been fixed with 32 CVEs assigned. In addition, JANUS achieves higher code coverage on all the file systems after fuzzing 12 hours, when compared with the state-of-the-art fuzzer Syzkaller for fuzzing file systems. JANUS visits 4.19x and 2.01x more code paths in Btrfs and ext4, respectively. Moreover, JANUS is able to reproduce 88–100% of the crashes, while Syzkaller fails on all of them.
Influence of Fluid Rheology on Blood Flow Haemodynamics in Patient-Specific Arterial Networks of Varied Complexity – In-Silico Studies

Abstract Results obtained with computational fluid dynamics (CFD) rely on assumptions made during a pre-processing stage, including a mathematical description of a fluid rheology. Up to this date there is no clear answer to several aspects, mainly related to the question of whether and under what conditions blood can be simplified to a Newtonian fluid during CFD analyses. Different research groups present contradictory results, leaving the question unanswered. Therefore, the objective of this research was to perform steady-state and pulsatile blood flow simulations using eight different rheological models in geometries of varying complexity. A qualitative comparison of shear- and viscosity-related parameters showed no meaningful discrepancies, but a quantitative analysis revealed significant differences, especially in the magnitudes of wall shear stress (WSS) and its gradient (WSSG). We suggest that for the large arteries blood should be modelled as a non-Newtonian fluid, whereas for the cerebral vasculature the assumption of blood as a simple Newtonian fluid can be treated as a valid simplification.
Laser constructed bulk oxygen vacancy caused high P doping for boosting the sodium‐storage capability

Defect‐assisted heteroatom doping can effectively enhance the intrinsic transfer characteristics of carriers in the crystal structure, which advantages over fast and efficient charge storage. In this work, a three‐dimensional self‐supporting titanium dioxide nanoparticle rich in bulk vacancies (L‐TiOx) on titanium substrate is synthesized by pulsed laser. Different from the surface vacancies, the bulk oxygen defects of L‐TiOx cause a uniform and bulk phosphorus (P) doping with a high concentration of ~5.71 at %, which endows the elevated electronic conductivity, and accelerates the transport of Na+. The obtained P‐doped L‐TiOx (LP‐TiOx) as an anode material in sodium‐ion batteries (SIBs) provides a reversible capacity of 400 mAh g−1 at 200 mA g−1, outstanding rate capability of 196 mAh g−1 at 10,000 mA g−1, and maintains stable performance over 1000 cycles. In situ X‐ray diffraction and ex situ high‐resolution transmission electron microscopy show that LP‐TiOx exhibits robust mechanical behavior with almost no lattice change under (de)sodiation. This work supplies a novel idea for high‐concentration bulk heteroatoms doping to enhance the electrochemical performance of SIBs.
The neuroimmune CGRP-RAMP1 axis tunes cutaneous adaptive immunity to the microbiota

The somatosensory nervous system surveils external stimuli at barrier tissues, regulating innate immune cells under infection and inflammation. The roles of sensory neurons in controlling the adaptive immune system, and more specifically immunity to the microbiota, however, remain elusive. Here, we identified a novel mechanism for direct neuroimmune communication between commensal-specific T lymphocytes and somatosensory neurons mediated by the neuropeptide Calcitonin Gene-Related Peptide (CGRP) in the skin. Intravital imaging revealed that commensal-specific T cells are in close proximity to cutaneous nerve fibers in vivo. Correspondingly, we observed upregulation of the receptor for the neuropeptide CGRP, RAMP1, in CD8+ T lymphocytes induced by skin commensal colonization. Neuroimmune CGRP-RAMP1 signaling axis functions in commensal-specific T cells to constrain Type 17 responses and moderate the activation status of microbiota-reactive lymphocytes at homeostasis. As such, modulation of neuroimmune CGRP-RAMP1 signaling in commensal-specific T cells shapes the overall activation status of the skin epithelium, thereby impacting the outcome of responses to insults such as wounding. The ability of somatosensory neurons to control adaptive immunity to the microbiota via the CGRP-RAMP1 axis underscores the various layers of regulation and multisystem coordination required for optimal microbiota-reactive T cell functions under steady state and pathology. Significance statement Multisystem coordination at barrier surfaces is critical for optimal tissue functions and integrity, in response to microbial and environmental cues. In this study, we identified a novel neuroimmune crosstalk mechanism between the sensory nervous system and the adaptive immune response to the microbiota, mediated by the neuropeptide CGRP and its receptor RAMP1 on skin microbiota-induced T lymphocytes. The neuroimmune CGPR-RAMP1 axis constrains adaptive immunity to the microbiota and overall limits the activation status of the skin epithelium, impacting tissue responses to wounding. Our study opens the door to a new avenue to modulate adaptive immunity to the microbiota utilizing neuromodulators, allowing for a more integrative and tailored approach to harnessing microbiota-induced T cells to promote barrier tissue protection and repair.
Genome-wide RNA structural determination in Candida yeast pathogens

Understanding the intricate roles of RNA molecules in virulence and host-pathogen interactions can provide valuable insights into combatting infections and improving human health. Although much progress has been achieved in understanding transcriptional regulation during host-pathogen interactions in diverse species, more is needed to know about the structure of pathogen RNAs. This is particularly true for fungal pathogens, including pathogenic yeasts of the Candida genus, which are the leading cause of hospital-acquired fungal infections. Deciphering the relation between RNA structure and their biology remains a significant gap. Despite advancements in transcriptional regulation studies, especially for fungal pathogens like Candida, the structural aspects of pathogenic RNAs remain understudied. Our work addresses this gap by employing genome-wide structure probing to comprehensively explore the structural landscape of mRNAs and long non-coding RNAs (lncRNAs) in the four major Candida pathogens. Specifically focusing on mRNA, we observe a robust correlation between sequence conservation and structural characteristics in orthologous transcripts, significantly when sequence identity exceeds 50%, highlighting structural feature conservation among closely related species. We investigate the impact of single nucleotide polymorphisms (SNPs) on mRNA secondary structure. SNPs within 5’ untranslated regions (UTRs) tend to occur in less structured positions, suggesting structural constraints influencing transcript regulation. Furthermore, we compare the structural properties of coding regions and UTRs, noting that coding regions are generally more structured than UTRs, consistent with similar trends in other species. Additionally, we provide the first experimental characterization of lncRNA structures in Candida species. Most lncRNAs form independent subdomains, similar to human lncRNAs. Notably, we identify hairpin-like structures in lncRNAs, a feature known to be functionally significant. Comparing hairpin prevalence between lncRNAs and protein-coding genes, we find enrichment in lncRNAs across Candida species, humans, and Arabidopsis thaliana, suggesting a conserved role for these structures. In summary, our study offers valuable insights into the interplay between RNA sequence, structure, and function in Candida pathogens, with implications for gene expression regulation and potential therapeutic strategies against Candida infections.
From Inhibition to Excitation and Why: The Role of Temporal Urgency in Modulating Corticospinal Activity

Previous research on movement preparation identified a period of corticospinal suppression about 200 ms prior to movement initiation. This phenomenon has been observed for different types of motor tasks typically used to investigate movement preparation (e.g., reaction time, self-initiated, and anticipatory actions). However, we recently discovered that this phenomenon is not observed when actions must be initiated under time pressure. In the present study, we investigated urgency effects on corticospinal suppression throughout the time course of an anticipatory timing task. Participants were required to perform timing actions under two urgency scenarios, high and low, and we applied single-pulse transcranial magnetic stimulation at different times during the time course of preparation. We analysed the time course of excitability under high and low scenarios in relation to expected and actual movement onset times. Our results confirmed our earlier findings that corticospinal suppression is not observed when participants perform actions under high urgency scenarios. In addition, we found no evidence that this preparatory suppression could be shifted in time to occur later under high urgency scenarios. Moreover, we found evidence that responses prepared under high urgency are more likely to be disrupted by external events (e.g., TMS pulses). These results suggest that preparatory suppression might be a strategy employed by the central nervous system to shield motor actions from interference of external events (e.g., loud sounds) when time allows. Given these data, we propose conceptual models that could account for the absence of preparatory suppression under time pressure to act.
Maf1 phosphorylation is regulated through the action of prefoldin-like Bud27 on PP4 phosphatase in Saccharomyces cerevisiae

Bud27 is a prefoldin-like protein that participates in transcriptional regulation mediated by the three RNA polymerases in Saccharomyces cerevisiae. Lack of Bud27 significantly affects RNA pol III transcription, although the involved mechanisms have not been characterized. Here we show that Bud27 regulates the phosphorylation state of the RNA pol III transcriptional repressor, Maf1, influences its nuclear localization, and likely its activity. We demonstrate that Bud27 is associated with the Maf1 main phosphatase PP4 in vivo, and that this interaction is required for proper Maf1 dephosphorylation. Lack of Bud27 decreases the interaction among PP4 and Maf1, Maf1 dephosphorylation, and its nuclear entry. Our data uncover a new nuclear function of Bud27, identify PP4 as a novel Bud27 interactor and demonstrate the effect of this prefoldin-like on the posttranslational regulation of Maf1. Finally, our data reveal a broader effect of Bud27 on PP4 activity by influencing, at least, the phosphorylation of Rad53.
Structure of the hepatitis C virus E1/E2 envelope proteins in a homodimeric complex

Worldwide, 58 million individuals suffer from chronic hepatitis C virus (HCV) infection, a primary driver of liver cancer. The HCV envelope proteins, E1 and E2, form a heterodimer, which is the target for neutralizing antibodies. Despite high-resolution structural models of partial heterodimer elements, the structural landscape of higher-order E1/E2 oligomers remains unexplored. We determined a ~3.5 Å cryo-electron microscopy structure of membrane-extracted HCV E1/E2 in a homodimeric arrangement. This structure includes detailed information on the homodimer interface, the E2-binding pocket for hypervariable region 1, antigenic site 412 conformation, and the organization of the E1/E2 transmembrane regions, including one internal to E1. This higher-order E1/E2 assembly could play a pivotal role in the design of novel vaccine antigens better mimicking E1/E2 complexes on the HCV particle.
Circuit mechanism underlying fragmented sleep and memory deficits in 16p11.2 deletion mouse model of autism

Sleep disturbances are prevalent in children with autism spectrum disorder (ASD) and have a major impact on the quality of life. Strikingly, sleep problems are positively correlated with the severity of ASD symptoms, such as memory impairment. However, the neural mechanisms underlying sleep disturbances and cognitive deficits in ASD are largely unexplored. Here, we show that non-rapid eye movement sleep (NREMs) is highly fragmented in the 16p11.2 deletion mouse model of ASD. The degree of sleep fragmentation is reflected in an increased number of calcium transients in the activity of locus coeruleus noradrenergic (LC-NE) neurons during NREMs. Exposure to a novel environment further exacerbates sleep in 16p11.2 deletion mice by fragmenting NREMs and decreasing rapid eye movement sleep (REMs). In contrast, optogenetic inhibition of LC-NE neurons and pharmacological blockade of noradrenergic transmission using clonidine reverse sleep fragmentation in 16p11.2 deletion mice. Furthermore, inhibiting LC-NE neurons restores memory. Rabies-mediated unbiased screening of presynaptic neurons reveals altered connectivity of LC-NE neurons with sleep- and memory regulatory brain regions in 16p11.2 deletion mice. Our findings reveal that heightened activity of LC-NE neurons and altered brain-wide connectivity underlies sleep fragmentation in 16p11.2 deletion mice and identify a crucial role of the LC-NE system in regulating sleep stability and memory in ASD.
Simultaneous detection of membrane contact dynamics and associated Ca2+ signals by reversible chemogenetic reporters

Membrane contact sites (MCSs) are hubs allowing various cell organelles to coordinate their activities. The dynamic nature of these sites and their small size hinder analysis by current imaging techniques. To overcome these limitations, we here designed a series of reversible chemogenetic reporters incorporating improved, low-affinity variants of splitFAST, and studied the dynamics of different MCSs at high spatiotemporal resolution, both in vitro and in vivo. We demonstrated that these versatile reporters suit different experimental setups well, allowing one to address challenging biological questions. Using these novel probes, we identified a hitherto unknown pathway, in which calcium (Ca2+) signalling dynamically regulates endoplasmic reticulum-mitochondria juxtaposition, characterizing the underlying mechanism. Finally, by integrating Ca2+-sensing capabilities into the splitFAST technology, we introduced PRINCESS (PRobe for INterorganelle Ca2+-Exchange Sites based on SplitFAST), an unprecedented class of reporters to simultaneously detect MCSs and measure the associated Ca2+ dynamics using a single biosensor.
Castration Model Illuminates Sex Differences in Healthy Aging: Insights from Metabolome and Transcriptome Analyses

Females typically outlive males, a disparity mitigated by castration, yet the molecular underpinnings remain elusive. Our study integrates multi-omics and behavioral analyses to uncover the pivotal compounds and genes influencing healthy aging post-castration, examining serum, kidney, and liver biospecimens from 12-week and 18-month old castrated male mice and their unaltered counterparts. Behavioral tests and LC-MS/MS metabolomics reveal that castrated males exhibit altered steroid hormones, superior cognitive performance, and higher levels of anti-oxidative compounds like taurine, despite identical diets. Integrated metabolome-transcriptome analysis confirms reduced lipid peroxidation and oxidative stress in female and castrated male mice, suggesting a protective mechanism against aging. Histological examinations post-cisplatin treatment highlight the model’s applicability in studying sex-dependent drug toxicity and reveal varying susceptibility in organ-specific toxicities, underlining the crucial role of sex hormones in physiological defenses. In essence, our castration model unveils a feminized metabolic and transcriptomic intermediary, serving as a robust tool for studying sex-specific aspects of healthy aging and exploring sex hormone-induced differences in diverse biomedical domains.
SECE: accurate identification of spatial domain by incorporating global spatial proximity and local expression proximity

Motivation Accurate identification of spatial domains is essential for analyzing spatial transcriptomics data to elucidate tissue microenvironments and biological functions. Existing methods utilize either local or global spatial relationships between spots to aid domain segmentation. A method that can concurrently capture both local and global spatial information may improve identification of spatial domains. Results In this article, we propose SECE, a deep learning-based method that captures both local and global relationships among spots and aggregates their information using expression similarity and spatial similarity. We benchmarked SECE against eight state-of-the-art methods on six real spatial transcriptomics datasets spanning four different platforms. SECE consistently outperformed other methods in spatial domain identification accuracy. Moreover, SECE produced spatial embeddings that exhibited clearer patterns in low-dimensional visualizations and facilitated more accurate trajectory inference. Availability and implementation SECE is implemented and provided as a pip installable Python package which is available on GitHub https://github.com/xie-lab/SECE.
Genetically encoded tool for manipulation of ΔΨm identifies the latter as the driver of integrative stress response induced by ATP Synthase dysfunction

Mitochondrial membrane potential (ΔΨm) is one of the key parameters controlling cellular bioenergetics. Investigation of the role of ΔΨm in live cells is complicated by a lack of tools for its direct manipulation without off-target effects. Here, we adopted the uncoupling protein UCP1 from brown adipocytes as a genetically encoded tool for direct manipulation of ΔΨm. We validated the ability of exogenously expressed UCP1 to induce uncoupled respiration and lower ΔΨm in mammalian cells. UCP1 expression lowered ΔΨm to the same extent as chemical uncouplers but did not inhibit cell proliferation, suggesting that it manipulates ΔΨm without the off-target effects of chemical uncouplers. Using UCP1, we revealed that elevated ΔΨm is the driver of the Integrated Stress Response induced by ATP synthase inhibition in mammalian cells.
Emerging dynamic regimes and tipping points from finite empirical principles

All dynamical systems are transient. The dynamics of our world at biogeochemical, ecological, and astronomical scales exist in a transient state because our planet, Sun, and universe are evolving toward thermodynamic equilibrium. However, predicting the tipping points associated with major dynamical shifts in these systems remains a significant challenge. Here, we introduce a new theoretical framework to predict tipping points. Our approach builds on two empirical principles: Observations occur over a finite time, and changes are perceptible when system variations are substantial relative to reference values. As a consequence, processes governing the dynamics of a system can become inactive over an observation time, and tipping points are reached when the processes switch off or on. The two principles were encoded mathematically, defining dynamic weights: contributions relative to reference values of the dynamic processes to the rate-of-change of agents in the system for a finite observational time. Operationally, processes were considered active if their weights were above a critical threshold. Tipping points were defined as reaching critical thresholds that activated or inactivated processes. This Finite Observational Dynamics Analysis Method (FODAM) method predicted that a system with n underlying dynamic processes could display 2n different dynamic regimes. However, the regimes depend on the observational time. The tipping points predicted the conditions for regime shifts and also the resilience of quasi-stable systems to perturbations. The application of FODAM was illustrated with a Lotka-Volterra predator-prey model featuring the interaction of bacteria and bacteriophage. A Colab notebook was also developed and deployed online to facilitate the application of the method to other systems. We conclude the article by discussing how our new approach bridges prior frameworks describing tipping point dynamics and critical transitions. We also outline the application of the method to empirical data to predict tipping points in complex systems.