Miracle-dz/UniFAR-FTUs huggingface dataset:
The IFIH1-A946T risk variant promotes diabetes in a sex-dependent manner

Type 1 diabetes (T1D) is an autoimmune disease in which pancreatic islet β-cells are attacked by the immune system, resulting in insulin deficiency and hyperglycemia. One of the top non-synonymous single-nucleotide polymorphisms (SNP) associated with T1D is in the interferon-induced helicase C domain-containing protein 1 (IFIH1), which encodes an anti-viral cytosolic RNA sensor. This SNP results in an alanine to threonine substitution at amino acid 946 (IFIH1A946T) and confers an increased risk for several autoimmune diseases, including T1D. We hypothesized that the IFIH1A946T risk variant, (IFIH1R) would promote T1D pathogenesis by stimulating type I interferon (IFN I) signaling leading to immune cell alterations. To test this, we developed Ifih1R knock-in mice on the non-obese diabetic (NOD) mouse background, a spontaneous T1D model. Our results revealed a modest increase in diabetes incidence and insulitis in Ifih1R compared to non-risk Ifih1 (Ifih1NR) mice and a significant acceleration of diabetes onset in Ifih1R females. Ifih1R mice exhibited a significantly enhanced interferon stimulated gene (ISG) signature compared to Ifih1NR, indicative of increased IFN I signaling. Ifih1R mice exhibited an increased frequency of plasma cells as well as tissue-dependent changes in the frequency and activation of CD8+ T cells. Our results indicate that IFIH1R may contribute to T1D pathogenesis by altering the frequency and activation of immune cells. These findings advance our knowledge on the connection between the rs1990760 variant and T1D. Further, these data are the first to demonstrate effects of Ifih1R in NOD mice, which will be important to consider for the development of therapeutics for T1D.
Balancing safety and efficiency in human decision making

The safety-efficiency dilemma describes the problem of maintaining safety during efficient exploration, and is a special case of the exploration-exploitation dilemma in the face of potentially catastrophic dangers. Conventional exploration-exploitation solutions collapse punishment and reward into a single signal, whereby early losses can be overcome by later gains. But the brain has a separate system for Pavlovian fear learning, suggesting a possible computational advantage to maintaining a specific fear memory during exploratory decision-making. In a series of simulations, we show here this promotes safe but efficient learning, and is optimised by arbitrating Pavlovian avoidance on instrumental decision-making according to uncertainty. In a human approach-withdrawal experiment, we show that this flexible avoidance model captures both choice and reaction times. These results show that the Pavlovian fear system has a more sophisticated role in decision-making that previously thought, by shaping flexible exploratory behaviour in a computationally precise manner.
Exploring functional connectivity in clinical and data-driven groups of preterm and term adults

Background Adults born very preterm (i.e., at <33 weeks’ gestation) are more susceptible to long-lasting structural and functional brain alterations and cognitive and socio-emotional difficulties, compared to full-term controls. However, behavioural heterogeneity within very preterm and full-term individuals makes it challenging to find biomarkers of specific outcomes. To address these questions, we parsed brain-behaviour heterogeneity in participants subdivided according to their clinical birth status (very preterm vs full-term) and/or data-driven behavioural phenotype (regardless of birth status). Methods The Network Based Statistic approach was used to identify topological components of resting state functional connectivity differentiating between i) 116 very preterm and 83 full-term adults (43% and 57% female, respectively), and ii) data-driven behavioural subgroups identified using consensus clustering (n= 156, 46% female). Age, sex, socio-economic status, and in-scanner head motion were used as confounders in all analyses. Post-hoc two-way group interactions between clinical birth status and behavioural data-driven subgrouping classification labels explored whether functional connectivity differences between very preterm and full-term adults varied according to distinct behavioural outcomes. Results Very preterm compared to full-term adults had poorer scores in selective measures of cognitive and socio-emotional processing and displayed complex patterns of hyper- and hypo-connectivity in subsections of the default mode, visual, and ventral attention networks. Stratifying the study participants in terms of their behavioural profiles (irrespective of birth status), identified two data-driven subgroups: An “At-risk” subgroup, characterised by increased cognitive, mental health, and socio-emotional difficulties, displaying hypo-connectivity anchored in frontal opercular and insular regions, relative to a “Resilient” subgroup with more favourable outcomes. No significant interaction was noted between clinical birth status and behavioural data-driven subgrouping classification labels in terms of functional connectivity. Conclusions Functional connectivity differentiating between very preterm and full-term adults was dissimilar to functional connectivity differentiating between the data-driven behavioural subgroups. We speculate that functional connectivity alterations observed in very preterm relative to full-term adults may confer both risk and resilience to developing behavioural sequelae associated with very preterm birth, while the localised functional connectivity alterations seen in the “At-risk” subgroup relative to the “Resilient” subgroup may underlie less favourable behavioural outcomes in adulthood, irrespective of birth status.
Regulatory T cells and IFN-γ-producing Th1 cells play a critical role in the pathogenesis of Sjögren’s Syndrome

Objectives Sjögren’s Disease (SjD) is an autoimmune disorder characterized by progressive dysfunction, inflammation and destruction of salivary and lacrimal glands, and by extraglandular manifestations. Its etiology and pathophysiology remain incompletely understood, though a role for autoreactive B cells has been considered key. Here, we investigated the role of effector and regulatory T cells in the pathogenesis of SjD. Methods Histological analysis, RNA-sequencing and flow cytometry were conducted on glands, lungs, eyes and lymphoid tissues of mice with regulatory T cell-specific deletion of stromal interaction proteins (STIM) 1 and 2 (Stim1/2Foxp3), which play key roles in calcium signaling and T cell function. The pathogenicity of T cells from Stim1/2Foxp3mice was investigated through adoptively transfer into lymphopenic host mice. Additionally, single-cell transcriptomic analysis was performed on peripheral blood mononuclear cells (PBMCs) of patients with SjD and control subjects. Results Stim1/2Foxp3 mice develop a severe SjD-like disorder including salivary gland (SG) and lacrimal gland (LG) inflammation and dysfunction, autoantibodies and extraglandular symptoms. SG inflammation in Stim1/2Foxp3 mice is characterized by T and B cell infiltration, and transcriptionally by a Th1 immune response that correlates strongly with the dysregulation observed in patients with SjD. Adoptive transfer of effector T cells from Stim1/2Foxp3 mice demonstrates that the SjD-like disease is driven by interferon (IFN)-γ producing autoreactive CD4+ T cells independently of B cells and autoantiboodies. scRNA-seq analysis identifies increased Th1 responses and attenuated memory Treg function in PBMCs of patients with SjD. Conclusions We report a more accurate mouse model of SjD while providing evidence for a critical role of Treg cells and IFN-γ producing Th1 cells in the pathogenesis of SjD, which may be effective targets for therapy.
Viral entry is a weak barrier to zoonosis

Recent advances in viral metagenomics have led to the discovery of many mammalian viruses, but experimental tests to determine whether they pose a threat to humans are largely lacking. A first step for a virus to cross the species barrier is to penetrate host cells. Here, we use gene synthesis and viral pseudotyping to experimentally test the ability of viral receptor-binding proteins (RBPs) from >100 enveloped RNA viruses to mediate entry into human cells. Analysis of thousands of RBP-cell pairs demonstrated such ability for most viruses, with significant variation among the 14 viral families studied. Comparison of RBP-mediated infectivity with cellular gene expression data showed that viral entry is often not limited by the presence of a receptor and revealed the contribution of additional host factors. Our results prove the weakness of interspecies barriers at the early stages of infection and identify molecular interactions that enable viral zoonosis.
A neural correlate of learning fails to predict foraging efficiency in Bombus terrestris

The mushroom bodies (MB) are integrative structures in the insect brain that, in social bees, contribute to both visual and olfactory learning. Changes in the density of presynaptic boutons (or microglomeruli) within the calyx region of the MB have been repeatedly linked to various aspects of foraging, including forms of learning that are thought to be key to support foraging efficiency. Here we set out to directly test the relationship between foraging efficiency and microglomerulus density in a bumblebee model, Bombus terrestris. We found no evidence that microglomerulus density predicted real-world foraging performance, nor any relationship with foraging experience. Instead, our data suggest a potential non-linear relationship between individual age, independent of foraging experience, and microglomerulus density in the lip region of the calyx, which is associated with olfactory processing. Our findings suggest that in real-world scenarios there is no simple direct relationship between microglomerular density, learning ability and foraging efficiency in bumblebees, highlighting the gap in knowledge regarding the relationships between learning abilities, neuroanatomy and foraging efficiency.
Transcriptomic Profile of Lin-Sca1+c-kit (LSK) cells in db/db mice with long-standing diabetes

The Lin-Sca1+c-Kit+ (LSK) fraction comprises multipotent hematopoietic stem cells (HSCs), vital to tissue homeostasis and vascular repair. While HSC homeostasis is impaired in diabetes, it is not known how chronic (>6 months) type 2 diabetes (T2D) alters the HSC transcriptome. Herein, we assessed the transcriptomic signature of HSCs in db/db mice employing mRNA and miRNA sequencing. We uncovered 2076 mRNAs and 35 miRNAs differentially expressed in db/db mice, including two novel miRNAs previously unreported in T2D. Further analysis of these transcripts showed a molecular shift with an increase in the pro-inflammatory cytokines and a decrease in anti-inflammatory cytokine expression. Also, pathway mapping unveiled inflammation and angiogenesis as one of the top pathways. These effects were reflected in bone marrow mobilopathy, retinal microglial inflammation, and neurovascular deficits in db/db mice. In conclusion, our study highlights that chronic diabetes alters HSCs’ at the transcriptomic level, thus potentially contributing to overall homeostasis and neurovascular deficits of diabetes, such as diabetic retinopathy. Highlights Bone marrow mobilopathy with long-standing diabetes Switch in LSK transcriptomic profile towards inflammation and angiogenesis Discovered 35 miRNAs, including two novel miRNAs, miR-3968 and miR-1971 LSK dysfunction reflected in inflammation and neurovascular deficits of the retina
Changes in spectral signature of leaves after desiccation: Implications for the prediction of leaf traits and plant-soil interaction in herbarium samples

The study investigated the impact of specimen desiccation on spectral signatures of plant tissue and its influence on models predicting biochemical and physiological traits, as well as ecosystem function. Analyzing 56 species, this study quantified the impact of leaf desiccation on: (1) the degree of change in the reflectance intensity, and its first and second derivatives within the visible - shortwave infrared spectrum, (2) the difference in change between wavebands used by Radiative Transfer Models (RTMs) for predicting traits in fresh leaves, (3) the prediction of leaf traits using PROSPECT RTM, and (4) the prediction of soil nutrient components from the leaf. Comparing desiccated specimens to fresh leaves, this study found the highest degree of change within the near infrared for the reflectance intensity, its first and second derivatives. Specific wavebands used for the prediction of leaf traits changed less that others in the VIS-SWIR. The prediction uncertainty for PROSPECT RTM differed for various leaf traits, showing an increase for equivalent water thickness, and carotene content, and a decrease in brown pigments and dry mass. Leaf traits predicted from desiccated leaves were better at predicting relationships with soil components, such as soil chemical properties and macro and micronutrients than fresh leaves. Desiccated leaves preserve and improves the capacity to inform us about important aspects of ecosystem functioning, particularly nutrient transfer between leaf and soil.
An inductive bias for slowly changing features in human reinforcement learning

Identifying goal-relevant features in novel environments is a central challenge for efficient behaviour. We asked whether humans address this challenge by relying on prior knowledge about common properties of reward-predicting features. One such property is the rate of change of features, given that behaviourally relevant processes tend to change on a slower timescale than noise. Hence, we asked whether humans are biased to learn more when task-relevant features are slow rather than fast. To test this idea, 100 human participants were asked to learn the rewards of two-dimensional bandits when either a slowly or quickly changing feature of the bandit predicted reward. Participants accrued more reward and achieved better generalisation to unseen feature values when a bandit’s relevant feature changed slowly, and its irrelevant feature quickly, as compared to the opposite. Participants were also more likely to incorrectly base their choices on the irrelevant feature when it changed slowly versus quickly. These effects were stronger when participants experienced the feature speed before learning about rewards. Modelling this behaviour with a set of four function approximation Kalman filter models that embodied alternative hypotheses about how feature speed could affect learning revealed that participants had a higher learning rate for the slow feature, and adjusted their learning to both the relevance and the speed of feature changes. The larger the improvement in participants’ performance for slow compared to fast bandits, the more strongly they adjusted their learning rates. These results provide evidence that human reinforcement learning favours slower features, suggesting a bias in how humans approach reward learning. Author Summary Learning experiments in the laboratory are often assumed to exist in a vacuum, where participants solve a given task independently of how they learn in more natural circumstances. But humans and other animals are in fact well known to “meta learn”, i.e. to leverage generalisable assumptions about how to learn from other experiences. Taking inspiration from a well-known machine learning technique known as slow feature analysis, we investigated one specific instance of such an assumption in learning: the possibility that humans tend to focus on slowly rather than quickly changing features when learning about rewards. To test this, we developed a task where participants had to learn the value of stimuli composed of two features. Participants indeed learned better from a slowly rather than quickly changing feature that predicted reward and were more distracted by the reward-irrelevant feature when it changed slowly. Computational modelling of participant behaviour indicated that participants had a higher learning rate for slowly changing features from the outset. Hence, our results support the idea that human reinforcement learning reflects a priori assumptions about the reward structure in natural environments.
Effects of D3-preferring agonist PD 128907 on compulsive behaviour and decision making as assessed by the 5C-CPT

Background Repetitive rituals in OCD patients result from pathological doubt, which has been linked to dysfunction in decision-making. First-line drug treatments for OCD are selective serotonin reuptake inhibitors; however, 40% of OCD patients do not respond to these. As brain activity patterns in OCD resemble those in schizophrenic patients, this suggests a dopaminergic component, supported by data showing that the D2/D3 receptor agonist Quinpirole induces compulsive checking in male rats. OCD has proved difficult to model in rodents and the contribution of decision making to compulsive behaviour in such models has not been studied. The five-choice continuous performance task (5C-CPT) measures both decision making and compulsive behaviour, making it possible to evaluate whether OCD models show correlated changes in these two behaviours. Establishing this would provide a new model approach to help develop therapeutic agents for OCD. Aims The role of dopaminergic D3 receptors in decision making and compulsive behaviour was determined by testing the effect of the preferential D3 agonist PD 128907 on 5C-CPT performance measures. Oldham’s method was used to determine the presence of any rate-dependent effect. Methods Female Lister hooded rats were trained to criterion in the 5C-CPT (>70% accuracy, < 30% omission and < 40% false alarms). The effects of PD128907 (0.25-1 mg/kg) were then investigated under challenging task conditions. Results Oldham method revealed: a moderate positive association between baseline perseverative correct responses and the change at 0.05 mg/kg PD 128907; a strong positive association between baseline perseverative false alarm and the change at 0.2 mg/kg; a positive association between baseline total number of perseverative responses and the change at 0.05 mg/kg or 0.2 mg/kg PD 128907; a positive relationship between baseline accuracy and the change at 0.05 mg/kg PD 128907; and a moderate positive association between baseline correct response latency and the change at 0.05 mg/kg or 0.2 mg/kg PD 128907. The angle measurements and the direction of movement (clockwise or counterclockwise) showed how effective is one dose at increasing compulsive behaviour compared with other doses. Conclusions PD 128907 effects on compulsive like behaviour and decision making in poor performing female lister hooded rats with long correct response latency and high perseveration at baseline (vulnerable population) in the 5C-CPT task matches two key features of OCD compulsions in humans (perseveration and indecision), this suggests that PD 128907 is more effective than Quinpirole in simulating the brain network conditions that underpin OCD. This model could help to develop more successful pharmacological interventions and to generate data translatable to clinical studies.
The Total Water Content of Sandy Beaches

Through the use of a Neutron Probe thermal neutron technique, shore-normal moisture profiles over a half tide cycle are presented from two contrasting Australian beaches. The theoretical notion of a saturated capillary fringe zone above the watertable is confirmed by the presence of a significant body of saturated sand above the watertable. This zone does not remain stable and simply rise with the rising watertable. When the rate of runup infiltration from above exceeds the rate of interstitial air expulsion, the striking phenomenon is observed of the watertable rising through a zone of unsaturated sand. Net changes in moisture profiles from low to high tide reveal that regarding any region in a beach as reverting from 'dry' to 'wet' is imprecise, rather the change is a more subtle variation in the 'degree of wetness'. The coincidence of the top of the saturated capillary fringe zone with the beachface results in the phenomenon known within hydrolgical texts as the 'reverse Wieringermeer effect'. This phenomenon accounts for the much misunderstood ability of the watertable to respond almost instantaneously to indi vidual swash events. In contrast to previously proposed large upward flow at velocities sufficient to fluidize the beachface, the minute addition of water to the sand surface induces an increase in pore-water pressure and by definition a rise of the watertable through the capillary fringe.
The geological record in non-marine environments around the K/T boundary (Tremp Formation, Spain)

In the Ager basin and Benabarre area (southern Pyrenees, Spain), the Cretaceous-Tertiary (K/T) boundary is recorded in a succession of non-marine to coastal deposits (Lower Tremp Formation). Abundant diverse dinosaur tracks have been found at two localities on top of an estuarine sandstone body. A few meters above, grey marls at two localities contain Palaeocene mammals and fish. Both levels are correlated with the latest part of chron C29R. These data have led to the location of the K/T boundary within a 3 m thick stratigraphic interval with no major breaks in the sedimentation. A rapid fall in delta 13 C content is recorded shortly after the K/T boundary. The delta 13 C curve does not support the hypothesis of a gradual shift due to volcanic activity. Both fossil vertebrates and isotope data are compatible with an abrupt change in the continental ecosystems close to the K/T boundary.
Remote Monitoring of Mines in Fields with Using Neural Networks

The work is devoted to the issue of humanitarian demining of agricultural lands. The difference between humanitarian demining and military demining is the lack of strict deadlines for the implementation of measures, as well as relatively small human and technical resources and large areas of monitoring. The situation is particularly difficult on marginal lands, which are poorly monitored by the local population and, accordingly, the establishment of minefields may be unexpected for farmers. Marginal lands are a potential source of energy raw materials for bioenergy, the importance of which is increasing in the modern conditions of the destruction of traditional logistics chains of supply of energy resources. The purpose of the work was to develop a method of express monitoring regarding the presence of mines in the fields. Operational research of large areas is possible precisely thanks to remote monitoring technologies, in particular thermal imaging. The hypothesis about the possibility of identifying mines due to the difference in the dynamics of heating and cooling of explosive objects under solar radiation during the day was tested. The research was conducted on the basis of the training ground of the military department of the National Academy of Sciences of Ukraine. TM-62M anti-tank mines, high-explosive shells caliber 125 mm, etc. were studied. When setting up the experiment, part of the ammunition was buried in the soil to a depth of 2-5 cm in accordance with the instructions for demining. It was established that only sunny days are suitable for thermal imaging monitoring, and samples installed in the shade were not identified. The maximum temperature difference for mines was recorded in the morning, and for massive shells in the evening. With regard to buried mines and projectiles, during thermal imaging monitoring, only depressions and bumps on the site were recorded. Based on the low selectivity of thermal imaging monitoring, neural networks were used to indicate mechanically laid mines on the ground. Positive results were obtained.