Miracle-dz/UniFAR-FTUs huggingface dataset:
Gain-of-function, focal segmental glomerulosclerosis Trpc6 mutation minimally affects susceptibility to renal injury in several mouse models

Mutations in TRPC6 are a cause of autosomal dominant focal segmental glomerulosclerosis in humans. Many of these mutations are known to have a gain-of-function effect on the non-specific cation channel function of TRPC6. In vitro studies have suggested these mutations affect several signaling pathways, but in vivo studies have largely compared wild-type and Trpc6-deficient rodents. We developed mice carrying a gain-of-function Trpc6 mutation encoding an E896K amino acid change, corresponding to a known FSGS mutation in TRPC6. Homozygous mutant Trpc6 animals have no appreciable renal pathology, and do not develop albuminuria until very advanced age. The animals show a slight delay in recovery from the albumin overload model. In response to chronic angiotensin II infusion, the mice have slightly greater albuminuria initially compared to wild-type animals, an effect that is lost at later time points, and a statistically non-significant trend toward more glomerular injury. This phenotype is nearly opposite to that of Trpc6-deficient animals previously described. The Trpc6 mutation does not appreciably impact renal interstitial fibrosis in response to either angiotensin II infusion, or folate-induced kidney injury. TRPC6 protein and TRPC6-agonist induced calcium influx could not be detected in glomeruli. In sum, these findings suggest that gain-of-function Trpc6 mutations confer only a mild susceptibility to glomerular injury in the mouse.
Mentalizing in economic games is associated with enhanced activation and connectivity in left temporoparietal junction

Studies in Social Neuroeconomics have consistently reported activation in regions associated with social cognition regions, such as the dorsomedial prefrontal cortex (dmPFC) and temporoparietal junction (TPJ) during decisions in interactive economic games, like the trust game. Activations in these regions have commonly been interpreted as reflecting mentalizing during economic choice that involves (strategic) uncertainty about what interaction partners, who can influence payouts, are going to do. Thus far, this theoretically plausible hypothesis is mainly supported by similar activation patterns in social cognition regions across different tasks that involve mentalizing, as identified by multiple meta-analyses. It remains important to test the involvement of neural activity associated with mentalizing in economic games within same sample of participants performing the same task. We designed a novel version of the classic false-belief task that is commonly used to induce mentalizing. This new task explicitly requires participants to infer beliefs of interaction partners while playing two economic games, the ultimatum game and the trust game. We compare activation patterns during the novel economic-games false-belief task to those during the classic story-based false-belief task using conjunction analyses. We find significant overlap in left TPJ, and dmPFC, as well as temporal pole during two task phases: when participants are reading about a sequence of events (belief formation) and when they answer an incentivized question about the interaction partners’ beliefs (belief inference). These results indicate that across the different task types and phases, mentalizing is associated with activation in social cognition regions. Moreover, effective connectivity analyses show that social cognition regions are interconnected during belief-formation and belief-inferences. Specifically, during belief formation, generalized psychophysiological interaction (gPPI) analyses indicate that right TPJ is a target of both left TPJ and right temporal pole (TP) seed regions, while during belief inferences all seed regions show interconnectivity with each other in ROI-to-ROI analyses. Our results support the notion that belief formation and inferences are supported by social cognitive processes in a wider network of social cognition regions that include bilateral TPJ, TP and dmPFC as central nodes. Importantly, this is the case in the context of economic games and standard false-belief tasks.
The cost of attentional reorienting on conscious visual perception: an MEG study

Do we need attention to become aware of external events? How do attentional networks influence conscious perception? How are spatial expectations implemented in frontoparietal networks? To answer these questions, we used magnetoencephalography (MEG) in human participants, and assessed the effects of spatially nonpredictive or predictive supra-threshold peripheral cues on the conscious perception of near-threshold Gabor patches. Three main results emerged. (1) As compared with invalid cues, both nonpredictive and predictive valid cues increased conscious detection. Yet, only predictive cues shifted the response criterion towards a more liberal decision and affected target contrast leading to 50% conscious detections. (2) Conscious perception of targets preceded by valid predictive cues was associated to enhanced activity in frontoparietal networks. These responses were lateralized to the left hemisphere during attentional orienting, and to the right hemisphere during target processing. The involvement of frontoparietal networks occurred earlier in valid than in invalid trials, a possible neural marker of the cost of re-orienting attention. (3) When detected targets were preceded by invalid predictive cues, and thus reorienting to the target was required, MEG responses occurred in left hemisphere temporo-occipital regions during attentional orienting, and in right hemisphere anterior insular and temporo-occipital regions during target processing. These results confirm and specify the role of frontoparietal networks in modulating conscious processing, and detail how orienting of spatial attention away from target location can disrupt conscious processing. Significance Statement Do we need to pay attention to external objects in order to become aware of them? Characterizing the spatiotemporal dynamics of attentional effects on visual perception is critical to understand how humans process and select relevant information. Participants detected near-threshold visual targets preceded by supra-threshold spatial cues with varying degrees of predictivity, while their brain activity was recorded using magnetoencephalography. Results demonstrated that valid predictive cues biased participants’ conscious perception through an early recruitment of frontoparietal regions, and that attentional costs associated to invalid predictive cues were related to activation of the right hemisphere ventral network. This work characterizes the neural dynamics associated with the cost of attentional reorienting on conscious processing.
Minimal requirements for a neuron to coregulate many properties and the implications for ion channel correlations and robustness

Neurons regulate their excitability by adjusting their ion channel levels. Degeneracy – achieving equivalent outcomes (excitability) using different solutions (channel combinations) – facilitates this regulation by enabling a disruptive change in one channel to be offset by compensatory changes in other channels. But neurons must co-regulate many properties. Pleiotropy – the impact of one channel on more than one property – complicates regulation because a compensatory ion channel change that restores one property to its target value often disrupts other properties. How then does a neuron simultaneously regulate multiple properties? Here we demonstrate that of the many channel combinations producing the target value for one property (the single-output solution set), few combinations produce the target value for other properties. Combinations producing the target value for two or more properties (the multi-output solution set) correspond to the intersection between single-output solution sets. Properties can be effectively co-regulated only if the number of adjustable channels (nin) exceeds the number of regulated properties (nout). Ion channel correlations emerge during homeostatic regulation when the dimensionality of solution space (nin – nout) is low. Even if each property can be regulated to its target value when considered in isolation, regulation as a whole fails if single-output solution sets do not intersect. Our results also highlight that ion channels must be co-adjusted with different ratios to regulate different properties, which suggests that each error signal drives modulatory changes independently, despite those changes ultimately affecting the same ion channels.
A multiplayer game model to detect insiders in wireless sensor networks

Insiders might have incentives and objectives opposed to those of the belonging organization. It is hard to detect them because of their privileges that partially protect them. In Wireless Sensor Networks (WSNs), significant security issues arise, including compromised nodes by insiders that disrupt the normal network operation. Immediate defensive actions to isolate malicious nodes would mitigate any related impacts. A multiplayer game model is proposed as a solution to the problem of insider attacks in WSNs, the Game of Wireless Sensor Networks (GoWiSeN). It is an imperfect information game, formulated with the use of non-cooperative game theory, holding the assumption that all players are rational. The model consists of several Local Intrusion Detection Systems (LIDSs), which are located to different nodes and communicate with a Global Intrusion Detection System (GIDS). Each LIDS gives suggestions whether the monitoring node is trusted or not. The game is being played between a potential attacker, the nodes and the GIDS. The GIDS is responsible for making a final decision and for isolating a compromised node in case of an internal attack. The theoretical model represents these interactions in an extensive form game. The formal elements of the game are specified, the outcomes of the game are quantified by first specifying players’ preferences, and then, by using the von Neumann-Morgenstern utility function, and payoffs are obtained. The game is constructed and solved, by locating NE in pure and mixed strategies. Experimental evaluations conducted on real network datasets, using IDSs of different capabilities, simulate special cases and compromised nodes in a WSN, verify the model efficiency, and show how the game should be played.
Role-Playing Between Environmental Pollutants and Human Gut Microbiota: A Complex Bidirectional Interaction

There is a growing interest in the characterization of the involvement of toxicant and pollutant exposures in the development and the progression of several diseases such as obesity, diabetes, cancer, as well as in the disruption of the immune and reproductive homeostasis. The gut microbiota is considered a pivotal player against the toxic properties of chemicals with the establishment of a dynamic bidirectional relationship, underlining the toxicological significance of this mutual interplay. In fact, several environmental chemicals have been demonstrated to affect the composition, the biodiversity of the intestinal microbiota together with the underlining modulated metabolic pathways, which may play an important role in tailoring the microbiotype of an individual. In this review, we aimed to discuss the latest updates concerning the environmental chemicals–microbiota dual interaction, toward the identification of a distinctiveness of the gut microbial community, which, in turn, may allow to adopt personalized preventive strategies to improve risk assessment for more susceptible workers.
Increased Expression of Tim-3 Is Associated With Depletion of NKT Cells In SARS-CoV-2 Infection

In the ongoing coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), natural killer T (NKT) cells act as primary initiators of immune responses. However, a decrease of circulating NKT cells has been observed in COVID-19 different stages, of which the underlying mechanism remains to be elucidated. Here, by performing single-cell RNA sequencing analysis in three large cohorts of COVID-19 patients, we found that increased expression of Tim-3 promotes depletion of NKT cells during the progression stage of COVID-19, which is associated with disease severity and outcome of patients with COVID-19. Tim-3+ NKT cells also expressed high levels of CD147 and CD26, which are potential SARS-CoV-2 spike binding receptors. In the study, Tim-3+ NKT cells showed high enrichment of apoptosis, higher expression levels of mitochondrial genes and caspase genes, with a larger pseudo time value. In addition, Tim-3+ NKT cells in COVID-19 presented a stronger capacity to secrete IFN-γ, IL-4 and IL-10 compared with healthy individuals, they also demonstrated high expression of co-inhibitory receptors such as PD-1, CTLA-4, and LAG-3. Moreover, we found that IL-12 secreted by dendritic cells (DCs) was positively correlated with up-regulated expression of Tim-3 in NKT cells in COVID-19 patients. Overall, this study describes a novel mechanism by which up-regulated Tim-3 expression induced the depletion and dysfunction of NKT cells in COVID-19 patients. These findings not only have possible implications for the prediction of severity and prognosis in COVID-19 but also provide a link between NKT cells and future new therapeutic strategies in SARS-CoV-2 infection.
Soil Microbiomes in Apple Orchards Are Influenced by the Type of Agricultural Management but Never Match the Complexity and Connectivity of a Semi-natural Benchmark

Conversion of natural ecosystems into agricultural land may strongly affect the soil microbiome and the functioning of the soil ecosystem. Alternative farming systems, such as organic farming, have therefore been advocated to reduce this impact, yet the outcomes of different agricultural management regimes often remain ambiguous and their evaluations mostly lack a proper more natural benchmark. We used high-throughput amplicon sequencing, linear models, redundancy analyses, and co-occurrence network analyses to investigate the effect of organic and integrated pest management (IPM) on soil fungal and bacterial communities in both the crop and drive rows of apple orchards in Belgium, and we included semi-natural grasslands as a benchmark. Fungi were strongly influenced by agricultural management, with lower diversity indices and distinct communities in IPM compared to organic orchards, whereas IPM orchards had a higher AMF abundance and the most complex and connected fungal communities. Bacterial diversity indices, community composition, and functional groups were less affected by management, with only a higher network connectivity and abundance of keystone taxa in organic drive rows. On the other hand, none of the agricultural soil microbiomes matched the complexity and connectedness of our semi-natural benchmark, demonstrating that even more nature-friendly agricultural management practices strongly affect the soil microbiome and highlighting the essential role of (semi-)natural systems as a harbor of robust and functionally diverse fungal and bacterial communities.
Soil and Climate Geographic Information System Data-Derived Risk Mapping for Grape Phylloxera in Washington State

Grape phylloxera (Daktulosphaira vitifoliae, syn. Viteus vitifoliae), a destructive root and foliar pest of grapevines, occurs in almost all viticulture regions worldwide. However, certain regions have remained “phylloxera free. ” Until recently, this included Washington state (United States), where this insect is regulated as a quarantine pest by Washington State Department of Agriculture. In 2019, established phylloxera populations were discovered in Washington. Phylloxera is typically managed by using resistant or tolerant rootstocks. In Washington, most wine grapes are grown on their own roots of the susceptible species Vitis vinifera instead of grafted rootstock, and thus, are at high risk of vine death should they become infested with phylloxera. This article reports development of a phylloxera risk map for Washington state using geographical soil texture (sand content) and soil temperature data. Weighted averages of soil texture data (mapping year: 2016, depth: 0–100 cm) were obtained from United States Department of Agriculture-Natural Resource Conservation Service (USDA-NRCS) and soilgrids. Soil temperature data were obtained from over 200 weather stations of Washington State University’s AgWeatherNet network. Threshold-based classifications were performed in Quantum GIS software on the rasterized soil sand content and temperature independently to derive low, moderate, and high-risk areas, with risk defined as site suitability for optimal phylloxera development. The validation identified 22 out of 23 confirmed phylloxera-positive sites as “high risk,” and one site as “moderate risk” when considering soil sand content alone. Soil temperature data alone classified 10 sites as “high risk” and 13 sites as “low risk. ” When soil sand content was combined with soil temperature (as a risk modifier), 10 sites were classified as “high risk,” 12 sites as “high-moderate risk” and one site as “moderate-low” risk. Ground-truth comparisons of confirmed positive sites for phylloxera agreed with past research suggesting that soil sand content is the dominant factor influencing phylloxera infestation. Pertinent risk assessment can be an important component for vineyard decision-making, including whether to use rootstocks in vineyard development or replant scenarios. It may also help to focus the initial scouting and identification efforts to sites and may be helpful when tracking and developing solutions for quarantine pests, such as phylloxera.
Examining the Relationship Between Basic Psychological Needs and Athlete Identity During the COVID-19 Pandemic

Objectives During COVID-19 athletes have had games canceled, seasons postponed, and social supports lost. These changes negatively impact their motivation, and potentially identity, as athletes. We draw on self-determination theory to examine motivation in sport and its relationship with athlete identity during COVID-19. Design A cross-sectional study design was employed consisting of online quantitative surveys. Method We gathered background engagement and motivation data from 115 athletes involved in organized sport. They responded to questions on basic psychological needs satisfaction (competence, relatedness, autonomy) and athlete identity. Results When reflecting on their basic psychological needs during the pandemic, most athletes considered them important. Athletes' competence and relatedness in sport were associated with social-related athlete identity, but not autonomy. Only relatedness in sport was associated with exclusivity-related social identity. Conclusions Using a self-determination theoretical lens, our findings contribute to understanding athlete motivation and identities when sport is interrupted.
Probiotic Bacillus subtilis LF11 Protects Intestinal Epithelium Against Salmonella Infection

Enteric diseases caused by Salmonella are prevalent in poultry farming. With the forbiddance of antibiotics in feedstuff industry, Bacillus subtilis (B. subtilis) preparation as antibiotic alternatives against Salmonella infection has gained increasing attention recently. However, the protection modes of B. subtilis against Salmonella infection in broilers are strain-specific. In this study, probiotic B. subtilis LF11 significantly reduced diarrhea and mortality of broilers caused by Salmonella braenderup (S. braenderup) in spite of no inhibition effect on it in vitro. Here, the intestinal epithelial cells NCM460 were incubated to explore the protection of B. subtilis LF11 on intestinal epithelium against Salmonella. The results revealed that B. subtilis LF11 showed obvious exclusion activity with the decrease of adhesion and invasion of S. braenderup to NCM460 cells, accordingly with the increase of NCM460 cell survival compared with S. braenderup challenge alone. Meanwhile, RT-PCR and Western blot proved that the gene transcription and expression levels of four tight junction proteins in NCM 460 cells were upregulated, which was further confirmed by immunofluorescence observation. Besides, B. subtilis LF11 downregulated the gene transcription levels of the proinflammatory cytokines IL-6, IL-8, and TNF-α induced by S. braenderup H9812. ELISA analysis also verified that B. subtilis LF11 reduced the IL-8 production significantly. In general, B. subtilis LF11 has the ability to protect the intestinal epithelium against Salmonella infection by reducing the Salmonella adhesion and invasion, enhancing the intestinal barrier and attenuating the enterocyte inflammatory responses, and has the potential as probiotics to prevent enteric diseases in broilers.
Local Demand, Quality of Place, and Urban Tourism Competitiveness

Most studies on tourism destination competitiveness examined the direct relationships of destination attributes and destination competitiveness. Few studies explored the intervening mechanisms between destination attributes and competitiveness. This study selected cities above the “alpha” level in the Globalization and World Cities Research Network rankings as samples to examine the relationship between local demand and urban tourism competitiveness mediated by the quality of place. Results showed that the relationship between urban wealth and tourist arrivals was completely mediated by the quality of place, while the mediating effect was not significant in the relationship between urban wealth and per capita tourism spending, though per capita tourism spending was directly and positively associated with urban wealth. In other words, richer cities had a higher quality of place, and a higher quality of place attracted more tourists but did not increase tourism per capita spending. Furthermore, the study found that there were two opposite influence paths of city size on urban tourism competitiveness. Although urban tourism competitiveness was directly and positively affected by population, the population had a significant negative effect on urban tourism competitiveness mediated by the quality of place. Through the quality of place, we can be aware of the indirect negative effect suppressed by the direct positive effect. This study revealed that the quality of place helped to better understand the competitiveness of urban tourism.