Miracle-dz/UniFAR-FTUs huggingface dataset:
Combined DiI and antibody labeling reveals complex dysgenesis of hippocampal spine synapses in a mouse model of Fragile X Syndrome

Structural, functional, and molecular alterations in excitatory spine synapses are a common hall-mark of many neurodevelopmental disorders including intellectual disability and autism. Here, we describe an optimized methodology, based on combined use of DiI and immunofluorescence, for rapid and sensitive characterization of the structure and composition of spine synapses in native brain tissue. We successfully demonstrate the applicability of this approach by examining the properties of hippocampal spine synapses in juvenile Fmr1 KO mice, a mouse model of Fragile X Syndrome. We find that mutant mice display pervasive dysgenesis of spine synapses evidenced by an overabundance of both abnormally elongated thin spines and cup-shaped spines, in combination with reduced density of mushroom spines. We further find that mushroom spines expressing the actin-binding protein Synaptopodin – a marker for spine apparatus - are more prevalent in mutant mice. Previous work identified spines with Synaptopodin/spine apparatus as the locus of mGluR-LTD, which is abnormally elevated in Fmr1 KO mice. Altogether, our data suggest this enhancement may be linked to the preponderance of this subset of spines in the mutant. Overall, these findings demonstrate the sensitivity and versatility of the optimized methodology by uncovering a novel facet of spine dysgenesis in Fmr1 KO mice.
Altered MAM function shifts mitochondrial metabolism in SOD1-mutant models of ALS

Mitochondrial defects are a common hallmark of familial and sporadic forms of amyotrophic lateral sclerosis (ALS). However, the origin of these defects, including reduced pyruvate metabolism and reduced oxygen consumption, is poorly understood. These metabolic functions are regulated in specialized endoplasmic reticulum (ER) domains in close contact with mitochondria, called mitochondrial-associated ER membranes (MAM). Recently it has been shown that MAM domains are disrupted in ALS, but the connection between MAM dysregulation and mitochondrial defects in ALS cells remains unclear. Using human embryonic stem cell (ESC)-derived motor neurons (hMNs) and mouse models with ALS-pathogenic mutations in superoxide dismutase 1 (SOD1), we found that the glycolytic deficiency in ALS is a direct consequence of the progressive disruption of MAM structure and function that hinders the use of glucose-derived pyruvate as a mitochondrial fuel and triggers a shift in mitochondrial substrates from pyruvate to fatty acids. This glycolytic deficiency, over time, induces significant alterations in mitochondrial electron flow and in the active/dormant (A/D) status of complex I in spinal cord, but not in brain. These data agree with a role for MAM in the maintenance and regulation of cellular glucose metabolism and suggest that MAM disruption in ALS could be the underlying cause of the bioenergetic deficits observed in the disease.
A high-resolution, nanopore-based artificial intelligence assay for DNA replication stress in human cancer cells

DNA replication stress is a hallmark of cancer that is exploited by chemotherapies. Current assays for replication stress have low throughput and poor resolution whilst being unable to map the movement of replication forks genome-wide. We present a new method that uses nanopore sequencing and artificial intelligence to map forks and measure their rates of movement and stalling in melanoma and colon cancer cells treated with chemotherapies. Our method can differentiate between fork slowing and fork stalling in cells treated with hydroxyurea, as well as inhibitors of ATR, WEE1, and PARP1. These different therapies yield different characteristic signatures of replication stress. We assess the role of the intra-S-phase checkpoint on fork slowing and stalling and show that replication stress dynamically changes over S-phase. This method requires sequencing on only a single nanopore flow cell, and the cost-effectiveness and high throughput enables functional screens to determine how human cancers respond to replication-targeted therapies.
Association between depression and sarcopenia in patients with heart failure [version 1; peer review: awaiting peer review]

Background: Prevalence of heart failure has been increasing worldwide. Decreased muscle mass, poor physical activity, and reduced physical performance or muscle strength might lead to sarcopenia among heart failure patients and therefore lead to low cardiac output, and vice versa. Symptoms of depression are also common mental health problems in heart failure. However, little is known about the prevalence of depressive symptoms in heart failure patients with sarcopenia and the relationship with its. This study aimed to explore the prevalence of and relationship between sarcopenia and depressive symptoms in heart failure patients. Methods: A cross-sectional study comprised of 150 participants aged 35 years or older. Sarcopenia and no sarcopenia were classified by using the Asian Working Group for Sarcopenia 2019 criteria. Physical performance, muscle strength, and skeletal muscle mass were examined. Symptoms of depression were assessed through utilization of the validated Thai version of Patient Health Questionnaire 9. Results: The prevalence of sarcopenia was 18.67% and depression was 5.33% in heart failure patients. In addition, the prevalence of depression in heart failure
Shifts in microbial communities do explain the response of grassland ecosystem function

composition treatments, but not the rainfall treatment. However, there was a strong effect of both rainfall change and plant functional group upon bacterial abundance. There was also a 45 weak interactive effect of the two treatments upon fungal community structure, although 46 fungal abundance was not affected by either treatment. Next, we used a statistical approach to assess whether treatment effects on ecosystem function were regulated by the microbial 48 community. Our results revealed that ecosystem function was influenced by the experimental 49 treatments, but was not related to associated changes to the microbial community. Overall, 50 these results indicate that changes in fungal and bacterial community structure and abundance 51 play a relatively minor role in determining ecosystem function responses to precipitation and 52 plant functional composition change, and that direct effects on soil physical and chemical 53 properties and upon plant and microbial physiology may play a more important role.
Disrupting the “empathy machine”: The power and perils of virtual reality in addressing social issues

This article looks through a critical media lens at mediated effects and ethical concerns of virtual reality (VR) applications that explore personal and social issues through embodiment and storytelling. In recent years, the press, immersive media practitioners and researchers have promoted the potential of virtual reality storytelling to foster empathy. This research offers an interdisciplinary narrative review, with an evidence-based approach to challenge the assumptions that VR films elicit empathy in the participant—what I refer to as the VR-empathy model. A review of literature from the fields of psychology, computer science, embodiment, medicine, and virtual reality was carried out to question and counter these claims through case studies of both fiction and non-fiction VR experiences. The results reveal that there is little empirical evidence of a correlation between VR exposure and an increase in empathy that motivates pro-social behavior, and a lack of research covering VR films exposure eliciting empathy. Furthermore, the results show an alarming lack of research into the long-term effects of VR films and other VR immersive experiences. This contribution aims to understand and demystify the current “empathy machine” rhetoric and calls for more rigorous, scientific research that can authenticate future claims and systemize ethical best practices.
Review of the action of organic matter on mineral sediment flocculation

Sediment is found throughout the world’s alluvial plain rivers, estuarine coasts and adjacent seas and is thereby a key factor in major ecosystems. Suspended mineral sediment can affect the biological activity of microorganisms and plants, by reducing light penetration in the water column or by binding to organic matter. Biological processes can, in turn, affect the physical and chemical properties of the sediment particles and influence the adhesion between particles. They can facilitate the sediment aggregation (flocculation) through bridging, patching and sweep, while biological decay will mainly help to disintegrate organic matter rich flocs. Biological activity also affects the properties of flocs (structure, density, sedimentation rate and composition). This activity is itself influenced by environmental conditions (like temperature, light and nutrient fluxes). Sediment flocculation thus involves complex relationships between several physical, chemical and biological factors. The role of biology in particular needs to be better integrated in sediment transport models, through the interaction between mineral clay particles, microorganisms and their excreted polymers (Extra Polymeric Substances, i.e., EPS). In this article, a summary of the state-of-the-art research regarding sediment flocculation is given. In particular, the action of organic matter on fine-grained sediment flocculation is discussed. The aim of the article is to provide a more comprehensive understanding of bio-sediment dynamics and give an outlook on remaining research questions.
Complementary effects of phosphorus supply and planting density on maize growth and phosphorus use efficiency

Phosphorus (P) supply and planting density regulate plant growth by altering root morphological traits and soil P dynamics. However, the compensatory effects of P supply and planting density on maize (Zea mays L.) growth and P use efficiency remain unknown. In this study, we conducted pot experiments of approximately 60 days to determine the effect of P supply, i.e., no P (CK), single superphosphate (SSP), and monoammonium phosphate (MAP), and different planting densities (low: two plants per pot; and high: four plants per pot) on maize growth. A similar shoot biomass accumulation was observed at high planting density under CK treatment (91.5 g plot–1) and low planting density under SSP treatment (94.3 g plot–1), with similar trends in P uptake, root morphological traits, and arbuscular mycorrhizal colonization. There was no significant difference in shoot biomass between high planting density under SSP (107.3 g plot–1) and low planting density under MAP (105.2 g plot–1); the corresponding P uptake, root growth, and P fraction in the soil showed the same trend. These results suggest that improved P supply could compensate for the limitations of low planting density by regulating the interaction between root morphological traits and soil P dynamics. Furthermore, under the same P supply, the limitations of low planting density could be compensated for by substituting MAP for SSP. Our results indicate that maize growth and P use efficiency could be improved by harnessing the compensatory effects of P supply and planting density to alter root plasticity and soil P dynamics.
Components of aircraft life support systems interact with each other and the user

The life support system in a tactical aircraft provides necessary supplemental oxygen to the aircrew. However, interactions among its various components may generate unexpected breathing loads. We focus here on the interactions between a regulator and breathing mask commonly used together in the U.S. Navy, the CRU-103 regulator and MBU 23/P mask, and some effects of the interactions on the user. The data reported were collected during a larger research effort examining potential physiological and cognitive effects of low regulator inlet pressures. Seventeen participants completed a series of tasks under mild exercise while breathing 40% O2 (balance N2) from an MBU-23/P mask supplied by a CRU-103 regulator with supply pressures 10, 6, 4, and 2 psig (CRU-103 specifications are for inlet pressures from 5 to 120 psig). Variables measured included flow to the mask and pressures at the regulator supply, in the hose to the mask, and in the mask. In addition to restricting inspiratory flow, low inlet pressure to the CRU-103 caused a counterintuitive overshoot in gas delivery pressure at end-inspiration, a mean increase of 1.5 cm H2O between the 10- and 2 psig conditions. The added pressure to the exhalation valve increased the expiratory threshold, the pressure to start expiratory flow, by approximately 2 cm H2O, increasing the effort needed to exhale.
Examining family processes linked to adolescent problem behaviors in single-mother families: The moderating role of school connectedness

Objective Previous research has shown that adolescents in single-mother households are at heightened risk for adjustment problems. However, limited studies have investigated the mechanisms leading to adolescent problem behaviors in single-mother households. To address this research gap, this study applied the Family Stress Model to examine how single mothers’ material hardship is linked to adolescent problem behaviors, focusing on the mediating roles of mothers’ depression and mother-adolescent closeness. The moderating role of adolescent school connectedness in the relationships between mother-adolescent closeness and school connectedness and between mothers’ depression and school connectedness was also investigated. Materials and methods The study analyzed data from 1,384 adolescents and their single mothers who participated in the Fragile Families and Child Wellbeing Study at Wave 6. The associations between study variables were analyzed using structural equation modeling by decomposing the direct, indirect, and total effects of material hardship on adolescent problem behaviors. School connectedness’s interactions with mother-adolescent closeness and mothers’ depression were also examined. Results Results showed a significant indirect relationship between material hardship and adolescent problem behaviors through sequential mediation of mothers’ depression and mother-adolescent closeness. Mothers’ depression also significantly mediated the relationship between material hardship and problem behaviors. Lastly, school connectedness moderated the relationship between mother-adolescent closeness and adolescents’ internalizing behaviors. The association between mother-adolescent closeness and adolescents’ internalizing behavior was weaker for adolescents with higher levels of school connectedness. Conclusion The results indicate the important indirect effect of economic strain on adolescents’ problems behaviors in single-mother households, which has been less emphasized compared to the effects in earlier childhood. High rates of material hardship and adolescent problem behaviors in single-mother families call for multifaceted interventions focusing on family processes and protective factors, including school environment.
The dual role of post-stop fundamental frequency in the production and perception of stops in Mandarin-English bilinguals

In non-tonal languages with a two-way laryngeal contrast, post-stop fundamental frequency (F0) tends to vary as a function of phonological voicing in stops, and listeners use it as a cue for stop voicing. In tonal languages, F0 is the most important acoustic correlate for tone, and listeners likewise rely heavily on F0 to differentiate tones. Given this ambiguity of F0 in its ability to signal phonological voicing and tone, how do speakers of a tonal language weight it in production and perception? Relatedly, do bilingual speakers of tonal and non-tonal languages use the same weights across different language contexts? To address these questions, the cross-linguistic performances from L1 (first language) Mandarin-L2 (second language) English bilinguals dominant in Mandarin in online production and perception experiments are compared. In the production experiment, the participant read aloud Mandarin and English monosyllabic words, the onsets of which typified their two-way laryngeal contrast. For the perception experiment, which utilized a forced-choice identification paradigm, both the English and Mandarin versions shared the same target audio stimuli, comprising monosyllables whose F0 contours were modeled after Mandarin Tone 1 and Tone 4, and whose onset was always a bilabial stop. The voice onset time of the bilabial stop and the onset F0 of the nucleus were manipulated orthogonally. The production results suggest that post-stop F0 following aspirated/voiceless stops was higher than that following unaspirated/voiced stops in both Mandarin and English production. However, the F0 difference in English was larger as compared to Mandarin, indicating that participants assigned more production weight to post-stop F0 in English than in Mandarin. On the perception side, participants used post-stop F0 as a cue in perceiving stops in both English and Mandarin, with higher post-stop F0 leading to more aspirated/voiceless responses, but they allocated more weight to post-stop F0 when interpreting audio stimuli as English words than as Mandarin words. Overall, these results argue for a dual function of F0 in cueing phonological voicing in stops and lexical tone across production and perception in Mandarin. Furthermore, they suggest that bilinguals are able to dynamically adjust even a secondary cue according to different language contexts.
Age-specific association between non-HDL-C and arterial stiffness in the Chinese population

Background While some epidemiological studies have found correlations between non-high-density lipoprotein cholesterol (non-HDL-C) and arterial stiffness, there are still exist controversial and age-stratified analysis are scarce yet. Methods All individuals in this study were recruited in the Third Xiangya Hospital of Central South University from 2012 to 2016. Arterial stiffness was defined as brachial-ankle pulse wave velocity (baPWV) ≥1,400 cm/s. Association between non-HDL-C and arterial stiffness were explored using Cox proportional-hazards model. We also conducted subanalysis stratified by age. Furthermore, restricted cubic splines were used to model exposure-response relationships in cohort sample. Results This cohort study included 7,276 participants without arterial stiffness at baseline. Over a median follow-up of 1.78 years (IQR, 1.03–2.49), 1,669 participants have identified with incident arterial stiffness. In multivariable-adjusted analyses, higher non-HDL-C concentration was associated with incident arterial stiffness with an adjusted hazard ratio (HR) of 1.09 [95% confidence interval (CI), 1.02–1.17] per 1 mmol/L increase. Compared with the lowest tertile, the HR for arterial stiffness with respect to the highest tertile of non-HDL-C was 1.26 (95% CI, 1.07–1.48). The results were similar in the analysis of young participants (age <60 years). Conclusion Our study identified that non-HDL-C as a potential risk factor of arterial stiffness, especially for younger. The clinical benefits of decreasing non-HDL-C concentration should be further considered in the future.
Effects of soil trace metals, organic carbon load and physicochemical stressors on active oxygen species metabolism in Scylla serrata sampled along the Bay of Bengal in Odisha state, India

Studies on the synergetic effects of soil and water parameters on Oxidative Stress (OS) physiology systems of the edible mud crab Scylla serrata sampled from different parts of East India are unknown. This study aimed to evaluate the effects of soil Ca, Mg, and organic carbon load and water physicochemical stressors induced spatio-temporal variation of tissue-specific OS and antioxidant parameters in S. serrata along the Bay of Bengal in Odisha. Spectrophotometric or Fourier-transform infrared spectroscopy methods were employed to measure the OS physiology and physicochemical parameters. Pedological and physicochemical factors of water were varied significantly in summer (38–42°C), rainy (25–35°C), and winter (12–20°C) seasons. Activities of antioxidant enzymes (AE) such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and the level of lipid peroxidation (LPx) were found to be higher in hepatopancreas as compared to other tissues irrespective of seasonal variation. Considering the impact of dry seasons, an average of 13.23% enhanced activities of AE were noticed in different tissues of S. serrata in response to temperature, salinity, organic carbon, Mg, and Ca load of sampling sites. However, about 11.26% decrease in the activities of AEs, including GR and GST in most of the tissues were recorded, along with a 21% alleviated level of LPx observed in the rainy season compared to other seasons. Among three coastal zones of the Bay of Bengal, the AEs in crabs sampled from Chandipur were elevated by 5.43% in winter, whereas a 7.05% enhanced level of LPx was found in summer compared to crabs sampled from Chilika and Jagatsinghpur. Overall, the levels of LPx, total antioxidant, and activities of AEs (CAT, GST, GPx, and GR) have shown a positive correlation, whereas ascorbic acid and GSH negatively correlate with habitat water pH, temperature, and salinity of soil and water. The results can be used for ecotoxic and environmental biomonitoring purposes using crabs as model organisms across tropical coastal regions.
de Broglie oscillation, rest mass and inertia

The model of a relativistic free massive point particle is investigated in the context of a Hamiltonian constraint system. It is shown that de Broglie oscillation, rest mass and inertia may be described within this model of Hamiltonian constraint system. PACS: 03.45. -w Newton’s classical mechanics and gravitational theory underwent remarkable changes after the advent of Einstein’s special and general theories of relativity. In these theories a 4-dimensional picture of our physical world was presented providing deep insight of man about the nature of physical laws. In this respect, a 4-dimensional description appeared as the key feature in investigation of the fundamental physical principles. It turned out that the 4-dimensional analysis of some physical phenomena may give the precise 3-dimensional descriptions of our experiences about them. The basic element in this 4-dimensional analysis was the abstract object called world line element. The invariance property of this object under Lorentz transformations or general coordinate transformations played the key role in developing special and general theories of relativity. Regarding the key role of the world line described above it is appealing to investigate more on this object in a rather abstract way. In this respect we are looking for some global features associated with the world line which may emerge due to an invariance symmetry called reparametrization invariance. We pay attention to the interesting role of this symmetry in investigation of the two mysteries in modern physics, namely de Broglie’s periodic phenomenon (oscillation) and the inertial properties of matter.