Miracle-dz/UniFAR-FTUs huggingface dataset:
A dialysis medium refreshment cell culture set-up for an osteoblast-osteoclast coculture

Culture medium exchange leads to loss of valuable auto- and paracrine factors produced by the cells. However, frequent renewal of culture medium is necessary for nutrient supply and to prevent waste product accumulation. Thus it remains the gold standard in cell culture applications. The use of dialysis as a medium refreshment method could provide a solution as low molecular weight molecules such as nutrients and waste products could easily be exchanged, while high molecular weight components such as growth factors, used in cell interactions, could be maintained in the cell culture compartment. This study investigates a dialysis culture approach for an in vitro bone remodeling model. In this model, both the differentiation of human mesenchymal stromal cells (MSCs) into osteoblasts and monocytes (MCs) into osteoclasts is studied. A custom-made simple dialysis culture system with a commercially available cellulose dialysis insert was developed. The data reported here revealed increased osteoblastic and osteoclastic activity in the dialysis groups compared to the standard non-dialysis groups, mainly shown by significantly higher alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) activity, respectively. This simple culture system has the potential to create a more efficient microenvironment allowing for cell interactions via secreted factors in mono- and cocultures and could be applied for many other tissues.
Can neural correlates of encoding explain the context dependence of reward‐enhanced memory?

Selective encoding can be studied by manipulating how valuable it is for participants to remember specific stimuli, for instance by varying the monetary reward participants receive for recalling a particular stimulus in a subsequent memory test. It would be reasonable for participants to strategically attend more to high-reward items compared to low-reward items in mixed list contexts, but to attend both types of items equally in pure list contexts, where all items are of equal value. Reward-enhanced memory may be driven by automatic dopaminergic interactions between reward circuitry and the hippocampus and thus be insensitive to list context; or it may be driven by meta-cognitive strategies, and thus context-dependent. We contrasted these alternatives by manipulating list composition, and tracked selective encoding through multiple EEG measures of attention and rehearsal. Behavioural results were context-dependent, such that recall of high-reward items was increased only in mixed lists. This result and aspects of the recall dynamics confirm predictions of the eCMR (emotional Context Maintenance and Retrieval) model. The power of ssVEPs was lower for high-reward items regardless of list composition, suggesting decreased visual processing of high-reward stimuli and that ssVEPs may index the modulation of context-to-item associations predicted by eCMR. By contrast, reward modulated the amplitude of Late Positive Potential and Frontal Slow Wave only in mixed lists. Taken together the results provide evidence that reward-enhanced memory is caused by an interplay between strategic processes applied when high- and low-reward items compete for cognitive resources during encoding and context-dependent mechanisms operating during recall.
An experimental and theoretical approach to understand the interaction between particles and mucosal tissues

Nanonization of poorly water-soluble drugs has shown great potential in improving their oral bioavailability by enhancing the dissolution rate and saturation solubility. Moreover, due to particle size reduction and larger surface area, the number of contact points with the gastrointestinal mucus favors adhesion. Similar phenomena could be anticipated when nano-pollutants come into direct contact with mucosal tissues. However, the fundamental features that govern the interaction of particles with mucus have not been investigated in a systematic and rational way before. In this work, we synthesize mucin hydrogels of different pore sizes with rheological properties that closely mimic the properties of freshly extracted porcine mucin. By using fluorescent pure curcumin particles, we characterize the effect of particle size (hydrodynamic diameter of 200 nm, and 1.2 and 1.3 μm), concentration (18, 35, and 71 μg mL−1), and hydrogel crosslinking density (which is directly related to the stiffness and governs the average pore size) on the diffusion-driven particle penetration in vitro. Next, we derive a phenomenological model that describes the physics behind the diffusion-derived penetration of particles into the mucin network and considers the contributions of the particle size, the particle concentration, and the crosslinking density of the mucin hydrogel. Finally, we challenge our experimental-theoretical approach by preliminarily assessing the oral pharmacokinetics of an anti-cancer model drug, namely dasatinib, in pristine and nanonized forms and two clinically relevant doses in rats. For of a dose of 10 mg kg−1, drug nanonization leads to a significant ~8- and ~21-fold increase of the drug oral bioavailability and half-life, respectively, with respect to the unprocessed micron-sized drug. When the drug dose of pure drug nanoparticles (which is directly related to the local concentration of the drug in the gastrointestinal tract) was increased to 15 mg mL−1, the oral bioavailability increased though not significantly, suggesting the saturation of the penetration sites in the mucus, as demonstrated by the in vitro model. Our overall results reveal the potential of this experimental-theoretical approach, shed light on the interaction of particulate matter and mucosal tissues, and pave the way for the development of tools that enable a more rational design of nano-drug delivery systems for mucosal administration and the assessment of risk factors related to the exposure of mucosal tissues to nano-pollutants.
Deep Learning Architectures For the Prediction of YY1-Mediated Chromatin Loops

YY1-mediated chromatin loops play substantial roles in basic biological processes like gene regulation, cell differentiation, and DNA replication. YY1-mediated chromatin loop prediction is important to understand diverse types of biological processes which may lead to the development of new therapeutics for neurological disorders and cancers. Existing deep learning predictors are capable to predict YY1-mediated chromatin loops in two different cell lines however, they showed limited performance for the prediction of YY1-mediated loops in the same cell lines and suffer significant performance deterioration in cross cell line setting. To provide computational predictors capable of performing large-scale analyses of YY1-mediated loop prediction across multiple cell lines, this paper presents two novel deep learning predictors. The two proposed predictors make use of Word2vec, one hot encoding for sequence representation and long short-term memory, and a convolution neural network along with a gradient flow strategy similar to DenseNet architectures. Both of the predictors are evaluated on two different benchmark datasets of two cell lines HCT116 and K562. Overall the proposed predictors outperform existing DEEPYY1 predictor with an average maximum margin of 4.65%, 7.45% in terms of AUROC, and accuracy, across both of the datases over the independent test sets and 5.1%, 3.2% over 5-fold validation. In terms of cross-cell evaluation, the proposed predictors boast maximum performance enhancements of up to 9.5% and 27.1% in terms of AUROC over HCT116 and K562 datasets.
The effects of oral supplementation of Japanese sake yeast on anxiety, depressive-like symptoms, oxidative stress, and BDNF changes in chronically stressed adolescent rats

Chronic stress during the pre-pubertal period has adverse effects in developing neuropsychiatric disorders such as depression and anxiety. The administration of supplements with antioxidant properties may alleviate depression and anxiety behavior. This study investigated the effects of oral supplementation of Japanese sake yeast on anxiety, depressive-like symptoms, oxidative stress, and changes in brain-derived neurotropic factor (BDNF) in adolescence rats subjected to chronic stress. In order to assess the effects of chronic stress, adolescent rats were grouped into one non-stressed control group (non-stress) and four different experimental groups. The other animals were subjected to stress and orally received normal saline (Control-stress), 15 mg/kg yeast (Stress-15), 30 mg/kg yeast (Stress-30) and 45 mg/kg yeast (Stress-45). Anxiety and depression-like behavior, BDNF levels, and oxidative stress markers were evaluated. The rats exposed to stress exhibited anxiogenic and depression-like behavior as well as lower levels of BDNF and higher levels of oxidative markers compared with non-stressed rats (P<0.05). However, the oral supplementation of sake yeast decreased anxiogenic and depression-like behavior and oxidative indices, and also increased BDNF levels compared to stressed rats treated with saline in a dose-dependent manner (P<0.05). In sum, stress caused anxiety and depression behavior, increased oxidative indices, and reduced BDNF levels while sake yeast alleviated adverse effects of stress on anxiety and depression behaviors, decreased oxidative markers, and increased BDNF levels.
Mitochondrial sodium/calcium exchanger NCLX regulates glycolysis in astrocytes, impacting on cognitive performance

Intracellular Ca2+ concentrations are strictly controlled by plasma membrane transporters, the endoplasmic reticulum, and mitochondria, in which Ca2+ uptake is mediated by the mitochondrial calcium uniporter complex (MCUc), while efflux occurs mainly through the mitochondrial Na+/Ca2+ exchanger (NCLX). RNAseq database repository searches led us to identify the Nclx transcript as highly enriched in astrocytes when compared to neurons. To assess the role of NCLX in mouse primary culture astrocytes, we inhibited its function both pharmacologically or genetically. This resulted in re-shaping of cytosolic Ca2+ signaling and a metabolic shift that increased glycolytic flux and lactate secretion in a Ca2+-dependent manner. Interestingly, in vivo genetic deletion of NCLX in hippocampal astrocytes improved cognitive performance in behavioral tasks, whereas hippocampal neuron-specific deletion of NCLX impaired cognitive performance. These results unveil a role for NCLX as a novel modulator of astrocytic glucose metabolism, impacting on cognition.
Improving 3D edge detection for visual inspection of MRI coregistration and alignment

Detecting and visualizing edges is important in several neuroimaging and medical imaging applications. For example, it is common to use edge maps to ensure the automatic alignment of low-resolution functional MRI images to match a high-resolution structural image has been successful. Specifically, software toolboxes like FSL and AFNI generate volumetric edge maps that can be particularly useful for visually assessing the alignment of datasets, overlaying the edge map of one on the other. Therefore, edge maps play a crucial role in quality assurance. Popular methods for computing edges are based on either the first derivative of the image as in FSL, or a variation of the Canny Edge detection method as implemented in AFNI. The crucial algorithmic parameter for adjustment for each of these methods relates to the image intensity. However, image intensity is relative and can be quite variable in most neuroimaging modalities. Further, the existing approaches do not necessarily generate a closed edge/surface, which can reduce the ability to determine the correspondence between a represented edge and another image. We suggest that using the second derivative (difference of Gaussian, or DoG) of the image to generate edges resolves both these issues. This method primarily operates by specifying a spatial scale of interest (which is typically known in medical imaging) rather than a contrast scale, and creates closed surfaces by definition. We describe some convenient implementation features (for both efficiency and visual quality) developed here, and we provide open source implementations of this method as both online and high performance portable code. Finally, we include this method as part of both the AFNI and FSL software packages.
Deficiency of the Heterogeneous Nuclear Ribonucleoprotein U locus leads to delayed hindbrain neurogenesis

Genetic variants affecting Heterogeneous Nuclear Ribonucleoprotein U (HNRNPU) have been identified in several neurodevelopmental disorders (NDDs). HNRNPU is widely expressed in the human brain and shows the highest postnatal expression in the cerebellum. Recent studies have investigated the role of HNRNPU in cerebral cortical development, but the effects of HNRNPU deficiency on cerebellar development remain unknown. Here, we describe the molecular and cellular outcomes of HNRNPU locus deficiency during in vitro neural differentiation of patient-derived and isogenic neuroepithelial stem cells with a hindbrain profile. We demonstrate that HNRNPU deficiency leads to chromatin remodeling of A/B compartments, and transcriptional rewiring, partly by impacting exon inclusion during mRNA processing. Genomic regions affected by the chromatin restructuring and host genes of exon usage differences show a strong enrichment for genes implicated in epilepsies, intellectual disability, and autism. Lastly, we show that at the cellular level. HNRNPU downregulation leads to altered neurogenesis and an increased fraction of neural progenitors in the maturing neuronal population. We conclude that, HNRNPU locus is involved in delayed commitment of neural progenitors to neuronal maturation in cell types with hindbrain profile.
Sustainable reference points for multispecies coral reef fisheries

Sustainably managing fisheries requires regular and reliable evaluation of stock status. However, most multispecies reef fisheries around the globe tend to be data-poor and lack research and monitoring capacity (e.g., long-term fishery data), preventing the estimation of sustainable reference points against which stocks can be assessed. Here, combining fish biomass data for more than 2000 coral reefs with catch estimates from 99 jurisdictions, we estimate site-specific sustainable reference points for coral reef fisheries and use these to assess the status of coral reef fish stocks. We reveal that more than half of jurisdictions with available information have stocks of conservation concern, having failed at least one fisheries sustainability benchmark. We quantify the trade-offs between biodiversity, mean fish length, and ecosystem functions relative to key benchmarks and highlight the ecological benefits of increasing sustainability. Our approach yields multispecies sustainable reference points for coral reef fisheries using environmental conditions, a promising means for enhancing the sustainability of the world’s coral reef fisheries. Teaser A global assessment of the sustainability of multispecies reef fisheries indicates that more than half of jurisdictions have failed at least one of two key sustainability benchmarks.
Acute stress impairs target enhancement but not distractor suppression in attention selection: Evidence from the N2pc and Pd

Acute stress has a profound impact on attention selection. However, the cognitive mechanism of acute stress on attention selection for neutral stimuli remains unclear. The current study aimed to investigate how acute stress affects target enhancement and distractor suppression in attention selection using a visual search task while EEG was recorded. The Maastricht Acute Stress Test was successfully induced a stress response in the stress group, as indexed by the higher salivary cortisol, state anxiety, and negative emotion. Crucially, the stress group showed significantly smaller N2pc than the control group in the lateral target/midline and contralateral distractor conditions when the distractor salience was high, whereas no significant differences in the Pd were observed in the lateral distractor/midline target condition. These results suggest that acute stress impairs target enhancement rather than distractor suppression in attention selection. This impairment may be due to the impaired function of the prefrontal cortex under acute stress. The present research provides the first insight into the cognitive mechanism of acute stress on attention selection.
Combined multidimensional single-cell protein and RNA profiling dissects the cellular and functional heterogeneity of thymic epithelial cells

The network of thymic stromal cells provides essential niches with unique molecular cues controlling T-cell development and selection. Recent single-cell RNA-sequencing studies uncovered a large transcriptional heterogeneity among thymic epithelial cells (TEC) demonstrating a previously unappreciated complexity. However, there are only very few cell markers that allow a comparable phenotypic identification of TEC. Here we deconvoluted by massively parallel flow cytometry and machine learning known and novel TEC phenotypes into novel subpopulations and related these by CITEseq to the corresponding TEC subtypes defined by the cells’ individual RNA profiles. This approach phenotypically identified perinatal cTEC, physically located these cells within the cortical stromal scaffold, displayed their dynamic change during the life course and revealed their exceptional efficiency in positively selecting immature thymocytes. Collectively, we have identified novel markers that allow for an unprecedented dissection of the thymus stromal complexity, the cells physical isolation and assignment of specific functions to individual TEC subpopulations.
Parthenogenomics: Insights on mutation rates and nucleotide diversity in parthenogenetic Panagrolaimus nematodes

Asexual reproduction is assumed to lead to the accumulation of deleterious mutations, and reduced heterozygosity due to the absence of recombination. Panagrolaimid nematode species display different modes of reproduction. Sexual reproduction with distinct males and females, asexual reproduction through parthenogenesis in the genus Panagrolaimus, and hermaphroditism in Propanagrolaimus. Here, we compared genomic features of free-living nematode populations in populations and species isolated from geographically distant regions to study diversity, and genome-wide differentiation under different modes of reproduction. We firstly estimated genome-wide spontaneous mutation rates in a triploid parthenogenetic Panagrolaimus population, and a diploid hermaphroditic Propanagrolaimus species via long-term mutation-accumulation-lines. Secondly, we calculated population genetic parameters including nucleotide diversity, and fixation index (FST) between populations of asexually and sexually reproducing nematodes. Thirdly, we used phylogenetic network methods on sexually and asexually reproducing Panagrolaimus populations to understand evolutionary relationships between them. The estimated mutation rate was slightly lower for the asexual population, as expected for taxa with this reproductive mode. Natural polyploid asexual populations revealed higher nucleotide diversity. Despite their common ancestor, a gene network revealed a high level of genetic differentiation among asexual populations. The elevated heterozygosity found in the triploid parthenogens could be explained by the third genome copy. Given their tendentially lower mutation rates it can be hypothesized that this is part of the mechanism to evade Muller’s ratchet. Our findings in parthenogenetic triploid nematode populations seem to challenge common expectations of evolution under asexuality.
Hounsfield unit for assessing asymmetrical loss of vertebral bone mineral density and its correlation with curve severity in adolescent idiopathic scoliosis

Background Low bone mass concomitantly occurs in patients with adolescent idiopathic scoliosis (AIS) and can persist until skeletal maturity. The purpose of this study was to assess the asymmetrical loss of vertebral bone mineral density (vBMD) and its correlation with curve severity in patients with AIS using Hounsfield unit (HU) values measured from computed tomography scans. Methods A total of 93 AIS patients were retrospectively recruited. The HU values of the vertebral body (VB-HU) and pedicle screw trajectory (PST-HU) were measured from four vertebrae above (Apex − 4) to four below (Apex + 4) the apical vertebra (Apex) of the major curve. The VB-HU and PST-HU at the upper end vertebra, Apex, and lower end vertebra within the concave and convex sides of the major and minor curves and stable vertebrae were obtained. Results A significant correlation was found between the Cobb angle and VB-HU at the periapical levels of the major curve. VB-HU and PST-HU at periapical levels were significantly greater within the concavity than the convexity of both major and minor curves. The asymmetric ratios of VB-HU and PST-HU were significantly correlated with the major curve Cobb angle, peaked at the apex, and gradually diminished from the apex to the end vertebrae. The asymmetrical loss of vBMD aggravated with the progression of curve severity, presenting as VB-HU, significantly decreased within the convexity and insignificantly decreased within the concavity of the major curve. Conclusion The asymmetrical loss of vBMD was associated with the progression of curve severity in AIS. For patients with severe AIS, the distraction of the pedicle screws at the concave side should be a priority in correcting the major curve, and supplemental anchors and larger-sized screws should be placed within the convex side around the apex of the major curve to reduce the risk of screw loosening after surgery.
The willingness to pay for agricultural irrigation water and the influencing factors in the Dujiangyan irrigation area: An empirical double-hurdle model analysis

Water prices are an efficient way to manage and allocate water resources. A scientific and reasonable water price standard can assist farmers to optimize their water allocations and ensure an efficient agricultural water system. However, under the current agricultural water pricing policy, it is difficult for water resource management departments to achieve sustainable operation because of unreasonable water price standards and the unwillingness of farmers to pay for agricultural irrigation water. Therefore, to ensure the sustainable management of agricultural water departments, it is important to design scientific and reasonable water price mechanisms that give full play to the regulatory role of agricultural water prices and encourage farmers to pay agricultural water fees. Based on survey data from 335 farming households in the Dujiangyan Irrigation Area, Sichuan, China, in 2019, a double-hurdle model was used to assess the willingness to pay for agricultural irrigation water. The willingness to pay was positively impacted by age, education level, willingness to participate, the arable land area, the water fee proportion, and water-saving awareness but negatively impacted by the water price standard and the farmers’ perceptions of the water price standard. Based on these results, to encourage farmers to participate in and afford agricultural water payments and to give full play to the water price adjustment function and other countermeasures, it is proposed that 1) water-saving awareness training be strengthened; 2) agricultural modernization be promoted; and 3) water price standards be scientifically and rationally formulated.